Shear wave elastography for assessing vascular walls

Abstract

A system and method of performing a therapeutic procedure, where a first neural block stimulation signal is applied to a blood vessel wall via electrodes on a distal portion of a therapeutic device located within the blood vessel, a change in vascular tone of the blood vessel is detected, and a therapy is applied to sympathetic nerves proximate the electrodes.

Description

SHEAR WAVE ELASTOGRAPHY FOR ASSESSING VASCULAR WALLS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No.63 / 571,711, filed March 29, 2024, the entire content of which is incorporated herein by reference.Technical Field

[0002] This disclosure relates to systems and methods assessing vascular walls using shear wave elastography.Background

[0003] Catheters have been proposed for use with various medical procedures. For example, a catheter can be configured to deliver neuromodulation (e.g., denervation) therapy to a target tissue site to modify the activity of nerves at or near the target tissue site. The nerves can be, for example, sympathetic or parasympathetic nerves. The sympathetic nervous system (SNS) is a primarily involuntary bodily control system typically associated with stress responses. Chronic over-activation of the SNS is a maladaptive response that can drive the progression of many disease states. For example, excessive activation of the renal SNS has been identified experimentally and in humans as a contributor to the complex pathophysiology of arrhythmias, hypertension, states of volume overload (e.g., heart failure), and progressive renal disease.

[0004] Percutaneous renal denervation is a minimally invasive procedure that can be used to treat hypertension and other diseases caused by over-activation of the SNS. During for example, a renal denervation procedure, a clinician delivers energy, such as radiofrequency, ultrasound, cooling, or other energy to a treatment site to reduce, and permanently stop the activity of nerves surrounding a blood vessel. The energy delivered to the treatment site may provide various therapeutic effects through alteration of sympathetic nerve activity.

[0005] Not all hypertensive patients are amenable to the denervation procedure described above. For example, patients suffering from vessel calcification are typically not responsive to interventional therapies like denervation and must be treated with changes in diet, medications, and other systemic approaches to reduce the patient’s hypertension. A variety of techniques have been developed attempting to ascertain whether a patient will respond positively to denervation, however, improvements are always desired.SUMMARY

[0006] A system of one or more computers can be configured to perform particular operations or actions by virtue of having software, firmware, hardware, or a combination of them installed on the system that in operation causes or cause the system to perform the actions. One or more computer programs can be configured to perform particular operations or actions by virtue of including instructions that, when executed by data processing apparatus, cause the apparatus to perform the actions. One general aspect of the disclosure is directed to The nerve denervation device also including a catheter configured to be inserted into a blood vessel, the catheter including at least one therapy delivery element coupled to a distal portion of the catheter; an ultrasound transducer, separate from the at least one therapy delivery element, configured to apply ultrasound energy to a wall of the blood vessel; and at least one shear wave detector configured to detect a shear wave portion of the ultrasound energy imparted on the wall of the blood vessel by the ultrasound transducer. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods.

[0007] Implementations may include one or more of the following features. The nerve denervation device where the at least one therapy delivery element may include at least one electrode, and where the catheter is configured to transform from a delivery configuration to a deployed configuration to place the at least one electrode in contact with the wall of the blood vessel. The catheter is configured to be advanced through the guide catheter. The at least one therapy delivery element coupled to the distal portion of the catheter is on the balloon. The at least one therapy delivery element may include at least one electrode, and where the at least one shear wave detector may include the at least one electrode. The ultrasound transducer and at least one shear wave detector are on a body of the catheter. The ultrasound transducer and at least one shear wave detector are on a second catheter configured to be inserted into the blood vessel. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium.

[0008] One further aspect is directed to a system for assessing likelihood of response to denervation therapy. The system includes a catheter configured for navigation within a blood vessel of a patient, the catheter including at least one therapy delivery element, an ultrasound transducer, and a shear wave detector; a therapy source in communication with the at least one therapy delivery element, a stimulation source in electrical communication with the at least one therapy delivery element and configured to supply nerve stimulation signals to the at least onetherapy delivery element and a wall of the blood vessel, a diagnostic source in electrical communication with the ultrasound transducer and configured to supply signals causing the ultrasound transducer to apply ultrasound energy to the wall of the blood vessel, a computing device including a processor and a memory storing therein instructions that when executed by the processor: generate in the diagnostic source and apply a first diagnostic signal to the ultrasound transducer to impart mechanical force on the blood vessel, detect shear waves in the blood vessel imparted by the mechanical force, determine whether the patient is likely to respond to denervation therapy based on the detected shear waves, and present on a user interface an indication of whether the patient is likely to respond to denervation therapy. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods.

[0009] Implementations may include one or more of the following features. The system where the computing device stores in the memory instructions that when executed by the processor determines an elasticity of the blood vessel. The computing device stores in the memory instructions that when executed by the processor generate in the therapy source and applies to the at least one therapy delivery element therapy to denervate the nerves enervating the blood vessel. The computing device stores in the memory instructions that when executed by the processor generate in the diagnostic source and apply a second diagnostic signal to the ultrasound transducer to impart mechanical force on the blood vessel. The computing device stores in the memory instructions that when executed by the processor determines a change in elasticity of the blood vessel as a result of the application of therapy. The computing device stores in the memory instructions that when executed by the processor determines that the change in elasticity of the blood vessel exceeds a threshold valve; and presents on the user interface an indication of success of the therapy based on the change in elasticity. The computing device stores in the memory instructions that when executed by the processor presents in the user interface an indication of expected patient response to the therapy based on the change in elasticity of the blood vessel. The computing device stores in the memory instructions that when executed by the processor presents in the user interface an indication of a need for additional therapy. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium.

[0010] Yet a further general aspect of the disclosure is directed to a system for assessing placement of a denervation therapy device. The system includes a catheter configured fornavigation within a blood vessel of a patient, the catheter including a therapy delivery element, an ultrasound transducer, and a plurality of shear wave detector; a therapy source in communication with a distal portion of the catheter, a stimulation source in electrical communication with the at least one therapy delivery element and configured to supply nerve stimulation signals to the at least one therapy delivery element and a wall of the blood vessel, a diagnostic source in electrical communication with the ultrasound transducer and configured to supply signals causing the ultrasound transducer to apply ultrasound energy to the wall of branches of the blood vessel, a computing device including a processor and a memory storing therein instructions that when executed by the processor: generate in the diagnostic source and apply a first diagnostic signal to the ultrasound transducer to impart mechanical force on branches of the blood vessel, detect first shear waves in the branches of the blood vessel imparted by the mechanical force, generate in the stimulation source and apply a first stimulation signal to the at least one therapy delivery element to stimulate nerves enervating the blood vessel, generate in the diagnostic source and apply a second diagnostic signal to the ultrasound transducer to impart mechanical force on branches of the blood vessel, detect second shear waves in the branches of blood vessel imparted by the mechanical force of the second diagnostic signal, determine whether the second shear waves are faster than the first shear waves for all shear wave detectors, and present on a user interface an indication of whether the nerves enervating the branch blood vessels also enervate the blood vessel. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods.

[0011] Further disclosed herein is a system and method of performing a therapeutic procedure, where a first neural block stimulation signal is applied to a blood vessel wall via electrodes on a distal portion of a therapeutic device located within the blood vessel, a change in vascular tone of the blood vessel is detected, and a therapy is applied to sympathetic nerves proximate the electrodes.

[0012] Implementations may include one or more of the following features. The system where the computing device stores in the memory instructions that when executed by the processor determines an elasticity of the branches of the blood vessel. The computing device stores in the memory instructions that when executed by the processor presents on the user interface an indication of potentially late attaching nerves in the branches of the blood vessel. The computing device stores in the memory instructions that when executed by the processorgenerate in the therapy source and applies to the at least one therapy delivery element a therapy signal to denervate the nerves enervating the blood vessel. The computing device stores in the memory instructions that when executed by the processor generate in the diagnostic source and apply a third diagnostic signal to the ultrasound transducer to impart mechanical force on the branches of the blood vessel, detect third shear waves in the branches of the blood vessel imparted by the mechanical force of the third diagnostic signal; determine whether the third shear waves are faster than the first shear wave or the second shear wave for all shear wave detectors; and present on the user interface an indication of whether the nerves enervating the branches of the blood vessel have been denervated or whether therapy needs to be applied in one or more of the branches of the blood vessel. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Various aspects and embodiments of the disclosure are described hereinbelow with references to the drawings, wherein:

[0014] FIG. l is a schematic diagram of a therapy system provided in accordance with some examples of the disclosure;

[0015] FIG. 2 is a schematic view of a workstation of the therapy system of FIG. 1;

[0016] FIG. 3 is a perspective view of a therapeutic device of the therapy system of FIG.1 advanced within a portion of the patient’s anatomy and in a deployed condition in accordance with some examples of the disclosure;

[0017] FIG. 4 is a flow chart depicting a method on accordance with examples of the disclosure;

[0018] FIGs. 5A and 5B are schematic representations of therapeutic device within a patient’s anatomy in accordance with the disclosure; and

[0019] FIG. 6 is a flow chart depicting a method on accordance with examples of the disclosure.DETAILED DESCRIPTION

[0020] This disclosure is directed to diagnostic and therapeutic systems and methods and particularly ablation systems and methods for identifying likely responsive patients and denervation or neuromodulation of nerves such as the sympathetic, or parasympathetic, nerves.

[0021] For ease of description, much of the following description focuses on implementations of ultrasound diagnostic and radiofrequency (RF) ablation and denervationmethodologies. Those having skill in the art will recognize that the methods and systems described herein may employ any of the therapy modalities described herein including without limitation monopolar or bipolar RF, microwave, ultrasound, chemical, cryogenic and other yet to be developed therapy modalities. Further, combinations of these therapies may be applied without departing from the scope of the disclosure. Similarly, the following description focuses on navigation to and application of therapy to the renal artery to assess vascular tone or stiffness and denervate sympathetic or, in certain embodiments, parasympathetic, nerves in, around, and proximate the renal arteries. However, the present disclosure is not so limited. In general, the devices, systems, and techniques described herein may be used in conjunction with neuromodulation (e.g., denervation) performed from within any suitable anatomical lumen that has nerves adjacent to the anatomical lumen. Example anatomical lumens include the celiac trunk and its branches (including the common hepatic artery and its branches (including the gastroduodenal artery and its branches, the right gastric artery and its branches, and the proper hepatic artery and its branches), the left gastric artery and its branches, and the splenic artery and its branches), the superior mesenteric artery and its branches, the gonadal artery and its branches, the inferior mesenteric artery and its branches, and the like. Further, although the disclosure primarily describes neuromodulation (e.g., denervation) from within one or more arteries, the devices, systems, and techniques of the disclosure also may be applied to neuromodulation from within one or more veins, such as a renal vein and its branches, a hepatic vein and its branches, an intercostal vein and its branches, or the like. In some implementations the devices, systems, and techniques described herein may be used to perform neuromodulation (e.g., denervation) from within two or more anatomical lumens, e.g., in the renal arteries and the common hepatic artery, or any other combination of two or more anatomical lumens, either simultaneously or sequentially. In addition, the systems, devices, and methods described herein may be useful in conjunction with neuromodulation (e.g., denervation) within a body lumen other than a vessel, for extravascular neuromodulation and / or for use in conjunction with therapies other than neuromodulation. Still further while generally contemplated that the locations described above are to be navigated to percutaneously, for example via the femoral artery, the therapeutic devices described herein may also be placed laparoscopically placed in or near one or more of the above-identified blood vessels, or another luminal tissue without departing from the scope of the present disclosure. Still further though described herein as employing intraluminal ultrasound for diagnostic aspects of the methods and systems, in someembodiments external ultrasound may be utilized without departing from scope of the disclosure.

[0022] Turning now to the drawings, FIG. 1 illustrates a therapy system provided in accordance with the present disclosure and generally identified by reference numeral 10. As shown in FIG. 1, therapy system 10 may be used in connection with a C-arm imaging system or other imaging station, which may facilitate navigation of a therapeutic device 50 to a desired location within the patient’ s anatomy (e.g. , the patient’ s renal artery), application of denervation therapy to the tissue within the renal artery to denervate sympathetic nerves within the tissue, and monitoring of impedance for use in evaluating the denervation therapy.

[0023] The therapy system 10 includes a workstation 20 and a therapeutic device 50 operably coupled to the workstation 20. The therapy system may be used with an imaging device 70, which may be operably coupled to a display 72. The patient “P” is shown lying on an operating table 12 with the therapeutic device 50 inserted through a portion of the patient’s femoral artery, although it is contemplated that the therapeutic device 50 may be inserted into any suitable portion of the patient’s vascular network that is in fluid communication with a desired blood vessel for therapy. Although generally described as having one therapeutic device 50, it is envisioned that the therapy system 10 may employ any suitable number of therapeutic devices 50. The therapeutic devices 50 may employ the same or different therapy modalities and be operably coupled to the workstation 20. Further, the therapeutic device 50 may employ a guidewire (now shown) or a guide catheter 58 (FIG. 3) without departing from the scope of the disclosure.

[0024] Continuing with FIG. 1 and with additional reference to FIG. 2, the workstation 20 includes a computer 22, a therapy source 24 (e.g., one or more of an RF generator, a microwave generator, an ultrasound generator, a cryogenic medium source, a chemical source, etc.) operably coupled to the computer 22. The workstation 20 also includes a stimulation source 24a (configured for generation of stimulation signals e.g., ultrasound, RF, etc.). Still further, the workstation 20 may include a diagnostic source 25. In accordance with aspects of the disclosure the diagnostic source 25 may be an ultrasound generator configured to generate signals which are received by an ultrasound transducer or transmitter causing the ultrasound transducer or transmitter to vibrate at the frequency of the received signal. In some examples, the computer 22, therapy source 24, stimulation source 24a, and diagnostic source 25 are integrated in a single component and may be referred to generally referred to as a generator.

[0025] The computer 22 is coupled to a display 26 that is configured to display one or more user interfaces 28. The computer 22 may be a desktop computer or a tower configuration with display 26 or may include a laptop computer or other computing device (including a generator). The computer 22 includes a processor 30 which executes software stored in a memory 32. The memory 32 may store one or more applications 34 and / or algorithms 44 to be executed by the processor 30. A network interface 36 enables the workstation 20 to communicate with a variety of other devices and systems via the internet. The network interface 36 may connect the workstation 20 to the Internet via a wired or wireless connection. Additionally, or alternatively, the communication may be via an ad hoc Bluetooth® or wireless network enabling communication with a wide-area network (WAN) and / or a local area network (LAN). The network interface 36 may connect to the Internet via one or more gateways, routers, and network address translation (NAT) devices. The network interface 36 may communicate with a cloud storage system 38, in which further data, image data, and / or videos may be stored. The cloud storage system 38 may be remote from or on the premises of the hospital such as in a control or hospital information technology room. It is envisioned that the cloud storage system 38 could also serve as a host for more robust analysis of acquired images (e.g., fluoroscopic, computed tomography (CT), magnetic resonance imaging (MRI), cone-beam computed tomography (CBCT), etc.), data, etc. (e.g., additional or reinforcement data for analysis and / or comparison). An input module 40 receives inputs from an input device such as a keyboard, a mouse, a remote control, voice commands, an energy source controller (e.g., a foot pedal or handheld remotecontrol device) that enables the clinician to initiate, terminate, and optionally, adjust various operational characteristics of the therapy source 24, stimulation source 24a, and / or diagnostic source 25, including, but not limited to, therapy delivery, stimulation delivery, or diagnostic delivery, amongst others. An output module 42 connects the processor 30 and the memory 32 to a variety of output devices such as the display 26. In some embodiments, the display 26 may be a touchscreen display and function as both an output device and an input device (e.g., the display 26 may be coupled to the input module 40).

[0026] The therapy source 24 generates and outputs one or more of RF energy (monopolar or bipolar), microwave energy, ultrasound energy, cryogenic energy, or chemical ablation medium via an automated control algorithm 44 stored on the memory 32 and / or under the control of a clinician. As can be appreciated, many of the therapies listed above change the temperature of the tissue (e.g, increase or decrease the temperature) to achieve the desired denervation of the nerves. The therapy source 24 may be configured to produce a selectedmodality and magnitude of energy and / or therapy for delivery to the treatment site via the therapeutic device 50, as will be described in further detail hereinbelow. The therapy source 24 may sense voltage and current applied to target tissue via the therapeutic device 50. In addition, one or more sensors on the therapeutic device 50 may monitor the temperature of the target tissue or tissue proximate the target tissue, and / or a portion of the therapeutic device 50. Utilizing the sensed voltage and current applied to the tissue, an application 34 on the computer 22 calculates an impedance of the tissue through which therapeutic energy is transmitted to provide an indication of the status of the tissue. This status may be output to the display 26 on one or more user interfaces 28 to provide a clinician with both intraprocedural and postprocedural feedback regarding the therapy.

[0027] In contrast with the therapy source 24, the stimulation source 24a outputs a non- therapeutic signal to effectuate an efferent response from the nerves in or near the location of the therapeutic device 50. In one example, the stimulation source 24a generates a low frequency stimulation signal. The low frequency stimulation signal may for example have a frequency of between 5 Hz and 40 Hz, a pulse width of been 3 and 10 ms, and a current of about 15 and 50 mA.

[0028] The low frequency stimulation signal from the stimulation source 24a may be a biphasic waveform where a leading phase of each successive pulse of the biphasic waveform is switched or otherwise inverted. In this manner, a biphasic waveform having an initial pulse with an anodal leading phase and a cathodal trailing phase is followed by a second pulse with a cathodal leading phase and an anodal trailing phase which will be followed by a third pulse returning to an anodal leading phase and a cathodal trailing phase, and so on. Alternatively, a biphasic waveform having an initial pulse with a cathodal leading phase and an anodal trailing phase may be followed by a second pulse with an anodal leading phase and a cathodal trailing phase which will be followed by a third pulse returning to a cathodal leading phase and an anodal trailing phase. The leading phase of each pulse of the biphasic waveform may be alternated for the duration of the application of neurostimulation to the target tissue. In this manner the stimulation source 24a generates a biphasic waveform at an energy level that is less the therapeutic (i.e., denervation energy) generated by the therapy source 24 such that the stimulation generated by the stimulation source 24a does not denervate the target tissue.

[0029] Like the stimulation source 24a, the diagnostic source 25 outputs a non-therapeutic signal. But rather than stimulating a response from the nerves enervating a blood vessel, the diagnostic source may include an ultrasound source, which generates a signal for supply to anultrasound transducer or transmitter. The signal (e.g., an RF signal at between 150 and 400 Hz) causes the transducer or transmitter to deform mechanically. This mechanical deformation of the transducer or transmitter propagates to tissue that is in contact with the transducer or transmitter generating waves within the tissue that propagate in a direction perpendicular to the direction of deformation of transducer or transmitter. In view of the magnitude of the mechanical deformation, the waves are not perceptible visually (e.g., via imaging) but can be detected via shear wave detectors. The detection of these waves, called shear waves, can be utilized to conduct a diagnostic referred to as elastography. Elastography assesses elasticity, the tendency of a material to resist deformation when a force is applied or to resume its original shape after removal of the force. In one aspect of the disclosure, as described in greater detail below, elastography provides a diagnostic indicator regarding whether a patient is likely to be a responder to neuromodulation and denervation procedures and further to assess tissue elasticity, specifically the elasticity or rigidity of blood vessels following therapy to provide an indicator of efficacy of the therapy.

[0030] FIG. 3 depicts one embodiment of a therapeutic device 50 in accordance with the disclosure. The therapeutic device 50 may be or may include a catheter. The therapeutic device 50 includes an elongated shaft 52 having a handle (not shown) disposed at or on a proximal end portion of the elongated shaft 52. The therapeutic device 50 includes an energy delivery assembly 54 on a distal portion of the elongate shaft 52 at which electrodes 56 are located. The elongated shaft 52 of the therapeutic device 50 is configured to be advanced over a guide wire (not shown) within a portion of the patient’s vasculature, such as a femoral artery or other suitable portion of patient’s vascular network that is in fluid communication with the patient’s renal artery. In embodiments, the energy delivery assembly 54 is configured to be transformed from an initial, undeployed configuration having a generally linear profile, to a second, deployed or expanded configuration, where the energy delivery assembly 54 forms a generally spiral and / or helical configuration for delivering energy to a site for application of therapeutic energy or application of stimulation signals at the treatment site. In this manner, when in the second, expanded configuration, the energy delivery assembly 54, and in particular the individual electrodes 56, is pressed against or otherwise contacts the walls of the patient’s vasculature tissue. Although generally described as transitioning to a spiral and / or helical configuration, it is envisioned that the energy delivery assembly 54 may be deployed in other configurations without departing from the scope of the present disclosure. Further, the therapeutic device 50 may be configurable, for example, using one or more pull wires (notshown) to adjust the configuration to promote contact between the electrodes 56 and the wall of the renal artery. As such, the therapeutic device 50 may be capable of being placed in one, two, three, four, or more different configurations depending upon the design needs of the therapeutic device 50 or the location at which therapy is to be applied. Still further, and without departing from the scope of the disclosure, the energy delivery assembly 54 and electrodes 56 may be formed on an exterior of an inflatable balloon, and expandable basket, a lasso, or a pigtail catheter to achieve the placement of the electrodes 56 in contact with the blood vessel wall without departing from the scope of the disclosure.

[0031] As depicted in FIG. 3, the elongated shaft 52 may be configured to be received within a portion of a guide catheter or guide sheath (such as a 6F guide catheter) 58 that is utilized to navigate the therapeutic device 50 to a desired location. In practice, the guide catheter 58 is inserted into an access point such as the femoral artery to gain access to the vascular system. The guide catheter 58 is advanced to the desired location, for example to cannulate a renal artery. A guide wire (not shown) is advanced through the guide catheter 58 and to a location where therapy is to be applied (i.e., beyond a distal end of the guide catheter 58) and into the desired blood vessel (e.g., the renal artery). The therapeutic device 50 is then advanced over the guide wire beyond the end of the guide catheter 58 exposing the electrodes 56 at the location where the therapy is to be applied. The guide wire is then retracted within the therapeutic device 50 and the guide catheter 58. Retraction of the guide wire within the therapeutic device 50 causes the energy delivery assembly 54 of the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (as shown in FIG. 3) with the electrodes 56 contacting the wall of the blood vessel. Though described herein as advancing the therapeutic device 50 beyond the guide catheter 58, in some configurations, the guide catheter 58 may be retracted relative to the therapeutic device 50 to achieve a desired placement of the electrodes 56 in contact with the blood vessel wall. Further, though described herein in connection with the use of a guide wire, the guide wire is not required, and the placement described herein above may be achieved without the use of the guide wire (e.g., with only a guide catheter). The elongated shaft 52 of the therapeutic device 50 may include an aperture (not shown) at a distal end thereof and configured to slidably receive the guidewire over which the therapeutic device 50, either alone or in combination with the guide catheter 58, are advanced. In this manner, the guidewire is utilized to guide the therapeutic device 50 to the target tissue using over-the-wire (OTW) or rapid exchange (RX) techniques, at which point the guide wire may be partially or fullyremoved from the therapeutic device 50, enabling the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (FIG. 3). As noted elsewhere herein, the therapeutic device 50 may transition from the first, undeployed configuration to the second, deployed configuration automatically (e.g., via a shape memory alloy, etc.) or manually (e.g., via pull wires, guide wire manipulation, etc. that is controlled by the clinician).

[0032] In some embodiments, a pressure sensor 60 may be incorporated into the guide sheath 58 alternatively a pressure sensor may be placed at a location on the elongated shaft 52 for detection of physiological parameters of the patient. In one example the physiological parameter is blood pressure though other parameters may be detected without departing from the scope of the disclosure.

[0033] In accordance with the disclosure, an ultrasound transducer 62 may be incorporated into the distal end of the of the elongated shaft 52. The ultrasound transducer 62 is in electrical communication with the diagnostic source 25. Signals from the diagnostic source 25 cause the ultrasound transducer to mechanically deform. The mechanical deformation based on the frequency and magnitude of the signal from the diagnostic source. As described above, the mechanical deformation of the ultrasound transducer 62 is applied to into the wall of the blood vessel and generates shear waves that travel along the length of the blood vessel and are detected by shear wave detectors that are incorporated into or if separately formed placed along the elongated shaft 52 (e.g., proximate each of the electrodes 56).

[0034] As illustrated in the figures, the electrodes 56 are disposed in spaced relation to one another along a length of the therapeutic device 50 forming the energy delivery assembly 54. As will be appreciated, these electrodes 56 are in communication with the therapy source 24 and the stimulation source 24a. The electrodes 56 may deliver therapy and / or stimulation independently of one another, simultaneously, selectively, or sequentially. The electrodes 56 may be in electrical communication with a ground pad (not shown) to enable the application of monopolar RF energy for therapy. Additionally or alternatively, therapy and / or stimulation energy may be applied between any desired combination of the electrodes 56, without requiring the use of a ground pad (e.g., bipolar RF). Further, when the shear wave detectors are incorporated into the electrodes 56, the electrodes 56 are also in electrical communication with the workstation 20. Shear waves detected by the electrodes 56 are converted to a signal that is transmitted to the workstation 20 and analyzed by an application 34 to measure the magnitude or speed of the shear waves. The speed of the shear waves provides a qualitative andquantitative estimate of the elasticity, rigidity, or stiffness of the blood vessel in which the shear waves are generated.

[0035] As noted above, shear wave elastography can be utilized to assess whether a patient is likely to respond to denervation therapies. Essentially this determination is an assessment of the stiffness of the blood vessel. Where the stiffness or lack of elasticity is in excess of a predetermined threshold, the patient’s hypertension is at least in part the result of an overactive SNS and not solely or predominantly as a result of calcification within the blood vessel. Accordingly, a patient expressing blood vessel stiffness in excess of this threshold is likely to positively respond to denervation therapies (e.g., experience a reduction in hypertension and related conditions). Further changes in elasticity or stiffness of the blood vessel can be detected before and after the application of therapy. While the overall efficacy of the therapy may take three to six months to fully manifest itself within the patient, changes in vessel stiffness will manifest nearly shortly after a denervation procedure. Thus, the detection of the changes in blood vessel stiffness, as a result of the therapy, qualifies the efficacy of the therapy and provides guidance on the expected results for the patient post-therapy.

[0036] In accordance with a further aspect of the disclosure when a therapeutic device 50 is placed within a blood vessel, measurement of changes of elasticity or stiffness, as a result of stimulation can provide guidance with regard to the proximity of nerves to the electrodes 56. Where a change in stiffness is detected as a result of the stimulation the clinician can confirm that the therapeutic device is placed at a location likely to result in a successful denervation. In yet a further aspect of the disclosure, where the therapeutic device 50 is placed in a main blood vessel, changes of stiffness to branches of the blood vessel as a result of stimulation can confirm that denervation in the main blood vessel will be effective in denervating the nerves that enervate the branches of the blood vessel. Such confirmation ensures that application of therapy in the main blood vessel will not miss any late attaching nerves (nerves that connect to the blood vessel only at or near the branches) which might limit the efficacy of the therapy applied only in the main blood vessel.

[0037] FIG. 4 depicts a method 400 where following navigation of a therapeutic device 50 to a desired location within a blood vessel of a patient (e.g., the main branch of the renal artery), at step 402 a diagnostic signal is generated by the diagnostic source 25 and transmitted to the ultrasound transducer 62. At step 404 the ultrasound transducer 62 imparts mechanical force on the blood vessel. At step 406 shear waves imparted on the blood vessel by the ultrasound transducer are detected by the shear wave detectors (e.g., electrodes 56). A signal representativeof the detected shear waves is transmitted to the computer 22. At step 408 an application 34 on the workstation 20 analyses the detected shear waves and determines the elasticity or rigidity of the blood vessel. At step 410, the application determines, based on the elasticity of the blood vessel whether the patient is likely to respond beneficially to therapy.

[0038] The output from the application 34 and displayed on the user interface 28 may include text and color indications as to the likelihood that the patient will have a positive respond to a denervation procedure (e.g., a drop in hypertension). The responsiveness may be based on the comparison of the determined elasticity or rigidity of the blood vessel to a threshold. As noted above, the elasticity of the blood vessel is assessed based on the speed of the shear waves traveling through the blood vessel. Thus, where the speed of the shear waves exceeds the threshold, the application 34 may determine that the patient is a likely responder to the therapy and presents an output on the user interface 28 at step 412. Where the patient is likely a responder, then output would include this fact and then therapy can be applied to the blood vessel at step 414, however, if the patient is not a responder an indication of may be presented on the user interface 28 at step 416 and the procedure ends.

[0039] Optionally, and in accordance with a further aspect of the disclosure, following application of therapy at step 418 a second diagnostic signal is generated by the diagnostic source 25 and transmitted to the ultrasound transducer 62. At step 420 the ultrasound transducer 62 imparts mechanical force on the blood vessel. At step 422 shear waves imparted on the blood vessel by the ultrasound transducer are detected by the shear wave detectors (e.g., electrodes 56). A signal representative of the detected shear waves is transmitted to the computer 22 and at step 424 the application 34 on the workstation 20 analyses the detected shear waves and determines the elasticity or rigidity of the blood vessel following therapy. At step 426 the application calculates a difference between the pre-therapy elasticity of the blood vessel and the post-therapy elasticity of a blood vessel (e.g., determining a change in elasticity between the elasticity determined at step 408 and the elasticity determined at step 424). At step 428, if the difference in elasticity is greater than a threshold the application 34 generates an output for display on the user interface 28 indicating that the therapy was a success and that the patient will likely respond positively to the therapy (e.g., experience a reduction in hypertension) over the coming months at step 430. Alternatively, if the difference is less than a threshold, this may be an indicator of late attaching nerves (e.g., nerves which only attach to the blood vessel at the blood vessel branch bifurcations or in the branch blood vessels themselves). Accordingly at step 432, an indicator may be generated by the application 34 andpresented on the user interface 28 that further therapy may be required or that absent further therapy the patient is unlikely to achieve the desired response to the therapy. At step 434 the therapeutic device 50 may be repositioned (e.g., rotated, or advanced into one or more of the blood vessel branches. Once repositioned the method returns to step 418 for the application of further therapy at the new location.

[0040] The method 400 may be continued either the threshold difference in elasticity or rigidity is achieved or until the main blood vessel and its branches have received therapy and insufficient change in elasticity is achieved. In either instance, the clinician is provided with information that can be used to advise the patient.

[0041] In a further aspect of the method 400, in addition to or as an alternative to the application of the second diagnostic signal. A stimulation signal may be generated by the stimulation source 24a and transmitted to the electrodes 56. In the event of a successful therapy, no or little change in blood vessel size should be observed (e.g., via fluoroscopic or ultrasound imaging). However, where unsuccessful or incomplete denervation, the blood vessel and / or branches thereof which receive the stimulation signal may in response to the stimulation reduce their diameter in response to the stimulation signal transmitting through untreated nerves enervating the blood vessel and / or branches thereof.

[0042] In still a further aspect of the disclosure, over time and based on the collection of data from hundreds and even thousands of patients a change in detected elasticity of the blood vessel as a result of therapy can be converted to an expected change in blood pressure for the patient. As will be appreciated, every patient is different and thus the change may be provided in terms of a range in expected blood pressure as a result of the therapy. This data may be shared with the patient following the procedure to provide guidance on the expected results from the therapy allowing better individual monitoring of the changes they experience and management of their expectations.

[0043] Yet a further aspect of the disclosure is depicted in FIGs. 5A and 5B where the therapeutic device 50 is placed within a main blood vessel 100, before the bifurcation leading to branch blood vessels 102. The therapeutic device 50 of FIGs. 5A and 5B have a different configuration than the therapeutic device 50 of FIG. 3. Rather than combined electrodes 56 and shear wave detectors, the therapeutic device has sperate shear wave detectors 64 arranged on a distal portion of the therapeutic device. Further, though depicted as a single therapeutic device 50, the ultrasound transducer 62 and the shear wave detectors 64 may be formed on a separate catheter navigated within the blood vessel of the patient.

[0044] Regardless of the construction, the therapeutic device 50 can be utilized in method 500 as shown in FIG. 6 to provide guidance on placement of the therapeutic device 50 within the blood vessel prior to application of therapy, and through the completion of therapy of a main blood vessel 100 and branch blood vessels 102. Method 500 describes a method of assessing the placement of the therapeutic device 50 within the blood vessel, and particularly to determine whether placement of the therapeutic device in the main blood vessel 100 will be effective for denervation of nerves enervating the branch blood vessels 102.

[0045] In accordance with method 500, following placement of the therapeutic device 50 within the main blood vessel 100, at step 502 a diagnostic signal is generated by the diagnostic source 25 and transmitted to the ultrasound transducer 62. At step 504 the ultrasound transducer 62 imparts mechanical force on the branch blood vessels 102. At step 506 shear waves imparted on the branch blood vessels 102 by the ultrasound transducer 62 are detected by the shear wave detectors 64 and signals representative of the detected shear waves are transmitted to the computer 22. At step 508 an application 34 on the workstation 20 analyses the detected shear waves and determines the initial elasticity or rigidity of the branch blood vessels 102. At step 510 a stimulation signal is generated by the stimulation source 24a and transmitted to the electrodes 56. Nerves within or near the main blood vessel 100 receive the stimulation signal. Where the main blood vessel 100 and the branch blood vessels 102 are enervated by the nerves receiving the stimulation signals, the main blood vessel 100 and the branch blood vessels will undergo vasoconstriction. Vasoconstriction is contraction of muscular layers within the blood vessel wall through which the nerves pass. While pressure sensors on the therapeutic device 50 can detect changes in blood pressure, and imaging modalities (e.g., fluoroscopy or ultrasound) can detect changes in blood vessel diameter, both of which are indicators of vasoconstriction, these methods may not be effective or may be difficult to employ, particularly for branch vessels 102. In accordance with method 500, at step 512 a second diagnostic signal is generated by the diagnostic source 25 and transmitted to the ultrasound transducer 62. At step 514 the ultrasound transducer 62 imparts mechanical force on the branch blood vessels 102. At step 516 shear waves imparted on the branch blood vessels 102 by the ultrasound transducer 62 are detected by the shear wave detectors 64 and a signal representative of the detected shear waves is transmitted to the computer 22. At step 518 an application 34 on the workstation 20 analyses the detected shear waves and determines whether speed of the shear waves from the second diagnostic signal detected by each shear wave detector 64 are greater than the shear waves from the first diagnostic signal. If the speed of the shear waves detectedat all of the shear wave detectors 64 is greater for the second diagnostic signal than the first diagnostic signal, then the therapeutic device is placed such that all or at least a substantial portion of the nerves enervating the branch vessels 102 can be denervated by application of therapy at the location of the therapeutic device.

[0046] At step 520 an indication that all of substantially all of the nerves enervating the branch blood vessel 102 also enervate the main blood vessel 100 may be presented in the user interface 28, and thus application of therapy will effectively denervate the nerves enervating both the main blood vessel 100 and the branch blood vessels 102 can be presented on the user interface 28. The method 500 proceeds to step 522 where a therapy signal is generated by the therapy source 24 and applied by the electrodes 56 to the main blood vessel wall. After application of the therapy at step 524 a second stimulation signal can be generated by the stimulation source 24a and applied via the electrodes 56 to the blood vessel wall. Following application of the second stimulation signal a third diagnostic signal can be generated by the diagnostic source 25 and transmitted to the ultrasound transducer 62 at step 526. At step 528 the ultrasound transducer 62 imparts mechanical force on the branch blood vessels 102. At step 530 shear waves imparted on the branch blood vessels 102 by the ultrasound transducer 62 are detected by the shear wave detectors 64 and a signal representative of the detected shear waves is transmitted to the computer 22. At step 532 the application 34 on the workstation 20 determines whether the speed of the shear waves from the third diagnostic signal detected by each shear wave detector 64 are less than the shear waves from the first and / or second diagnostic signal. If the speed of the shear waves detected at all of the shear wave detectors 64 is less for the third diagnostic signal than the first and / or second diagnostic signal, then the therapy can be determined by the application 34 to be successful and an indication of the success is displayed on the user interface 28 a step 534. A successful denervation in one in which all or substantially all of the nerves enervating the branch blood vessels 102 have been successfully denervated by denervation of the nerves enervating the main blood vessel 100.

[0047] If, however, at step 532 not all of the shear waves detected by the shear wave detectors 64 as a result of the third diagnostic signal are slower than those detected as a result of the first and / or second diagnostic signal, then the user interface 28 may display at step 536 an indicator that one or more of the branch vessels 102 require application of therapy within the branch vessel 102. At step 538, following re-positioning of the therapeutic device 50 to one of the branch vessels which was indicated as requiring further therapy, therapy may be applied to the nerves enervating the branch vessel 102 by generation of a therapeutic signal from thetherapy source and application to wall of the branch blood vessel 102 via the electrodes 56. At step 540 a fourth diagnostic signal can be generated by the diagnostic source 25 and transmitted to the ultrasound transducer 62. At step 542 the ultrasound transducer 62 imparts mechanical force on the branch blood vessels 102. At step 544 shear waves imparted on the branch blood vessels 102 by the ultrasound transducer 62 are detected by the shear wave detectors 64 and a signal representative of the detected shear waves is transmitted to the computer 22.

[0048] At step 546 the application 34 on the workstation 20 determines whether the speed of the shear waves from the fourth diagnostic signal detected by each shear wave detector 64 are less than the shear waves from the first and / or second diagnostic signal. If the speed of the shear waves detected at all of the shear wave detectors 64 is less for the fourth diagnostic signal than the first and / or second diagnostic signal, then the therapy can be determined by the application 34 to be successful and an indication of the success is displayed on the user interface 28 a step 548. If, however, the speed of the shear waves detected at all of the shear wave detectors 64 is not less for the fourth diagnostic signal than the first and / or second diagnostic signal, then the therapy can be determined by the application 34 to be un-successful or at least incomplete and an indication of such may be presented on the user interface 28 at step 550. This may indicate that nerves which enervate the blood vessel branches 102 are particularly late attaching to the blood vessel branches 102 and the therapeutic device 50 may be again repositioned and an indicator of such may be presented on the user interface 28. The method may then optionally return to step 546 in an attempt to denervate these late attaching nerves, for example, by advancing the therapeutic device 50 further into the blood vessel branch 102 or the method may end. Additionally or alternatively, where at step 546 even if it is determined that the denervation is incomplete, a qualification of the expected patient response to the denervation based on the detected change in elasticity or stiffness between the first diagnostic signal and the second, third, or fourth diagnostic signals and the determined changes in shear wave speeds. This qualitative assessment may be presented on the user interface 28 as part of step 550. In some instances, it may be determined that though incomplete, the denervation was none the less sufficient to achieve a desirable reduction in hypertension such that continuing further in the method is not required and the procedure may stop.

[0049] Referring back to the determination at step 518, when it is determined that not all of the shear waves detected by shear wave detectors 64 following the application of the stimulation signal are faster than the shear waves detected prior to application of the stimulation signal, then the user interface 28 may display an indication that one or more of the blood vesselbranches 102 is enervated by late attaching nerves at step 552. As noted elsewhere, late attaching nerves are those which enervate one or more of the blood vessel branches 102 without enervating the main blood vessel 100. Accordingly, application of denervation therapy to the main blood vessel 100 will not be effective in denervating all or substantially all of the nerves, the over stimulation of which, resulting in or at least contributing to the patient’s hypertension. The clinician then has a choice, to either apply therapy to the main blood vessel 100 and to one or more of the blood vessel branches 102, as described substantially herein above (e.g., steps 520-550).

[0050] Alternatively, the clinician may advance the therapeutic device 50 a first of blood vessel branches 102 and steps 538-550 may be undertaken to apply therapy to the first blood vessel branch 102. These steps may be repeated for each of the blood vessel branches 102 to achieve denervation in each blood vessel branch 102. Following step 550, an optional step 551 may inquire whether additional blood vessel branches 102 require denervation, if yes the method again returns to step 526 until all of the blood vessel branches 102 receive therapy and the changes in the elasticity or rigidity of the branch blood vessels 102 is achieved in each blood vessel branch 102.

[0051] While both methods 400 and 500 are described in detail above, steps of each method may be skipped or undertaken in a different order than as presented or with one or more of the steps eliminated without departing from the scope of the disclosure. Further, steps of method 400 may be incorporated into method 500 and steps from method 500 incorporated into method 400 without departing from the scope of the disclosure.

[0052] Heretofore, the therapeutic device 50 has been primarily described in connection with a shape memory construction where exit from a guide catheter 58 frees the shape memory to achieve a desired spiral and / or helical shape of the distal end and place the electrodes 56 against the blood vessel walls as depicted in FIG. 3. However, the present disclosure is not so limited and the therapeutic device 50 may be formed such that the electrodes are placed on a balloon or other expanding mechanism to achieve the desired contact with the blood vessel walls without departing from the scope of the disclosure.

[0053] Although described generally hereinabove, it is envisioned that the memory 32 may include any non-transitory computer-readable storage media for storing data and / or software including instructions that are executable by the processor 30 and which control the operation of the workstation 20 and, in some embodiments, may also control the operation of the therapeutic device 50. In an embodiment, memory 32 may include one or more storage devicessuch as solid-state storage devices, e.g., flash memory chips. Alternatively, or in addition to the one or more solid-state storage devices, the memory 32 may include one or more mass storage devices connected to the processor 30 through a mass storage controller (not shown) and a communications bus (not shown).

[0054] The description of computer-readable media contained herein refers to solid-state storage. It should be appreciated by those skilled in the art that computer-readable storage media can be any available media that can be accessed by the processor 30. That is, computer readable storage media may include non-transitory, volatile, and non-volatile, removable, and nonremovable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules or other data. For example, computer-readable storage media may include RAM, ROM, EPROM, EEPROM, flash memory or other solid-state memory technology, CD-ROM, DVD, Blu-Ray or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which may be used to store the desired information, and which may be accessed by the workstation 20.EXAMPLES

[0055] The disclosure is further described in connection with the following examples in which:Example 1 - A nerve denervation device including a catheter configured to be inserted into a blood vessel, the catheter including at least one therapy delivery element coupled to a distal portion of the catheter, an ultrasound transducer, separate from the at least one therapy delivery element, configured to apply ultrasound energy to a wall of the blood vessel, and at least one shear wave detector configured to detect a shear wave portion of the ultrasound energy imparted on the wall of the blood vessel by the ultrasound transducer.Example 2 - The nerve denervation device of example 1, wherein the at least one therapy delivery element comprises at least one electrode, and wherein the catheter is configured to transform from a delivery configuration to a deployed configuration to place the at least one electrode in contact with the wall of the blood vessel.Example 3 - The nerve denervation device of any one of the preceding examples, further including a guide catheter, wherein the catheter is configured to be advanced through the guide catheter.Example 4 - The nerve denervation device of any one of the preceding examples, further including a balloon, wherein the at least one therapy delivery element coupled to the distal portion of the catheter is on the balloon.Example 5 - The nerve denervation device of any one of the preceding examples, wherein the at least one therapy delivery element comprises at least one electrode, and wherein the at least one shear wave detector comprises the at least one electrode.Example 6 - The nerve denervation device of any one of the preceding examples, wherein the ultrasound transducer and at least one shear wave detector are on a body of the catheter. Example 7 - The nerve denervation device of examples 1-5 wherein the ultrasound transducer and at least one shear wave detector are on a second catheter configured to be inserted into the blood vessel.Example 8 - A system for assessing likelihood of response to denervation therapy including, a catheter configured for navigation within a blood vessel of a patient, the catheter including at least one therapy delivery element, an ultrasound transducer, and a shear wave detector, a therapy source in communication with the at least one therapy delivery element, a stimulation source in electrical communication with the at least one therapy delivery element and configured to supply nerve stimulation signals to the at least one therapy delivery element and a wall of the blood vessel, a diagnostic source in electrical communication with the ultrasound transducer and configured to supply signals causing the ultrasound transducer to apply ultrasound energy to the wall of the blood vessel, a computing device including a processor and a memory storing therein instructions that when executed by the processor, generate in the diagnostic source and apply a first diagnostic signal to the ultrasound transducer to impart mechanical force on the blood vessel, detect shear waves in the blood vessel imparted by the mechanical force, determine whether the patient is likely to respond to denervation therapy based on the detected shear waves, and present on a user interface an indication of whether the patient is likely to respond to denervation therapy.Example 9 - The system of example 8, wherein the computing device stores in the memory instructions that when executed by the processor determines an elasticity of the blood vessel. Example 10 - The system of examples 8 or 9, wherein the computing device stores in the memory instructions that when executed by the processor generate in the therapy source and applies to the at least one therapy delivery element therapy to denervate the nerves enervating the blood vessel.Example 11 - The system of examples 8-10, wherein the computing device stores in the memory instructions that when executed by the processor generate in the diagnostic source and apply a second diagnostic signal to the ultrasound transducer to impart mechanical force on the blood vessel.Example 12 - The system of examples 8-11, wherein the computing device stores in the memory instructions that when executed by the processor determines a change in elasticity of the blood vessel as a result of the application of therapy.Example 13 - The system of examples 8-12, wherein the computing device stores in the memory instructions that when executed by the processor determines that the change in elasticity of the blood vessel exceeds a threshold valve and presents on the user interface an indication of success of the therapy based on the change in elasticity.Example 14 - The system of examples 8-13, wherein the computing device stores in the memory instructions that when executed by the processor presents in the user interface an indication of expected patient response to the therapy based on the change in elasticity of the blood vessel.Example 15 The system of examples 8-13, wherein the computing device stores in the memory instructions that when executed by the processor presents in the user interface an indication of a need for additional therapy.Example 16 - A system for assessing placement of a denervation therapy device including a catheter configured for navigation within a blood vessel of a patient, the catheter including a therapy delivery element, an ultrasound transducer, and a plurality of shear wave detector, a therapy source in communication with a distal portion of the catheter, a stimulation source in electrical communication with the at least one therapy delivery element and configured to supply nerve stimulation signals to the at least one therapy delivery element and a wall of the blood vessel, a diagnostic source in electrical communication with the ultrasound transducer and configured to supply signals causing the ultrasound transducer to apply ultrasound energy to the wall of branches of the blood vessel, a computing device including a processor and a memory storing therein instructions that when executed by the processor, generate in the diagnostic source and apply a first diagnostic signal to the ultrasound transducer to impart mechanical force on branches of the blood vessel, detect first shear waves in the branches of the blood vessel imparted by the mechanical force, generate in the stimulation source and apply a first stimulation signal to the at least one therapy delivery element to stimulate nerves enervating the blood vessel, generate in the diagnostic source and apply a second diagnosticsignal to the ultrasound transducer to impart mechanical force on branches of the blood vessel, detect second shear waves in the branches of blood vessel imparted by the mechanical force of the second diagnostic signal, determine whether the second shear waves are faster than the first shear waves for all shear wave detectors, and present on a user interface an indication of whether the nerves enervating the branch blood vessels also enervate the blood vessel.Example 17 - The system of example 16, wherein the computing device stores in the memory instructions that when executed by the processor determines an elasticity of the branches of the blood vessel.Example 18 - The system of examples 16 or 17, wherein the computing device stores in the memory instructions that when executed by the processor presents on the user interface an indication of potentially late attaching nerves in the branches of the blood vessel.Example 19 - The system of examples 16-18, wherein the computing device stores in the memory instructions that when executed by the processor generate in the therapy source and applies to the at least one therapy delivery element a therapy signal to denervate the nerves enervating the blood vessel.Example 20 - The system of examples 16-19, wherein the computing device stores in the memory instructions that when executed by the processor generate in the diagnostic source and apply a third diagnostic signal to the ultrasound transducer to impart mechanical force on the branches of the blood vessel, detect third shear waves in the branches of the blood vessel imparted by the mechanical force of the third diagnostic signal, determine whether the third shear waves are faster than the first shear wave or the second shear wave for all shear wave detectors, and present on the user interface an indication of whether the nerves enervating the branches of the blood vessel have been denervated or whether therapy needs to be applied in one or more of the branches of the blood vessel.

[0056] While several embodiments of the disclosure have been shown in the drawings, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise. Therefore, the above description should not be construed as limiting, but merely as exemplifications of embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

Claims

CLAIMS:

1. A nerve denervation device comprising: a catheter configured to be inserted into a blood vessel, the catheter including at least one therapy delivery element coupled to a distal portion of the catheter; an ultrasound transducer, separate from the at least one therapy delivery element, configured to apply ultrasound energy to a wall of the blood vessel; and at least one shear wave detector configured to detect a shear wave portion of the ultrasound energy imparted on the wall of the blood vessel by the ultrasound transducer.

2. The nerve denervation device of claim 1, wherein the at least one therapy delivery element comprises at least one electrode, and wherein the catheter is configured to transform from a delivery configuration to a deployed configuration to place the at least one electrode in contact with the wall of the blood vessel.

3. The nerve denervation device of any one of the preceding claims, further comprising a guide catheter, wherein the catheter is configured to be advanced through the guide catheter.

4. The nerve denervation device of any one of the preceding claims, further comprising a balloon, wherein the at least one therapy delivery element coupled to the distal portion of the catheter is on the balloon.

5. The nerve denervation device of any one of the preceding claims, wherein the at least one therapy delivery element comprises at least one electrode, and wherein the at least one shear wave detector comprises the at least one electrode.

6. The nerve denervation device of any one of the preceding claims, wherein the ultrasound transducer and at least one shear wave detector are carried by a body of the catheter.

7. The nerve denervation device of any one of claims 1 to 5, wherein the ultrasound transducer and the at least one shear wave detector are on a second catheter configured to be inserted into the blood vessel.

8. A system for assessing likelihood of response to denervation therapy comprising; a catheter configured for navigation within a blood vessel of a patient, the catheter including at least one therapy delivery element, an ultrasound transducer, and a shear wave detector; a therapy source in communication with the at least one therapy delivery element; a stimulation source in electrical communication with the at least one therapy delivery element and configured to supply nerve stimulation signals to the at least one therapy delivery element and a wall of the blood vessel; a diagnostic source in electrical communication with the ultrasound transducer and configured to supply signals causing the ultrasound transducer to apply ultrasound energy to the wall of the blood vessel; a computing device including a processor and a memory storing therein instructions that when executed by the processor cause the processor to: cause the diagnostic source to generate a first diagnostic signal and output the first diagnostic signal to the ultrasound transducer to impart mechanical force on the blood vessel; receive signal indicative of a detected shear wave in the blood vessel imparted by the mechanical force; determine whether the patient is likely to respond to denervation therapy based on the detected shear wave; and present on a user interface an indication of whether the patient is likely to respond to denervation therapy.

9. The system of claim 8, wherein the computing device stores in the memory instructions that when executed by the processor cause the processor to determine an elasticity of the blood vessel.

10. The system of claim 8 or 9, wherein the computing device stores in the memory instructions that when executed by the processor cause the processor to cause the therapy source to generate and output to the at least one therapy delivery element therapy to denervate nerves surrounding the blood vessel.

11. The system of any one of claims 8 to 10, wherein the computing device stores in the memory instructions that when executed by the processor cause the processor to cause the diagnostic source to generate and output a second diagnostic signal to the ultrasound transducer to impart mechanical force on the blood vessel.

12. The system of any one of claims 8 to 11, wherein the computing device stores in the memory instructions that when executed by the processor cause the processor to determine a change in elasticity of the blood vessel as a result of the application of therapy.

13. The system of any one of claims 8 to 12, wherein the computing device stores in the memory instructions that when executed by the processor cause the processor to: determine that the change in elasticity of the blood vessel exceeds a threshold valve; and present on the user interface an indication of success of the therapy based on the change in elasticity.

14. The system of any one of claims 8 to 13, wherein the computing device stores in the memory instructions that when executed by the processor cause the processor to present in the user interface an indication of expected patient response to the therapy based on the change in elasticity of the blood vessel.

15. The system of any one of claims 8 to 13, wherein the computing device stores in the memory instructions that when executed by the processor cause the processor to present in the user interface an indication of a need for additional therapy.

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