Blood volume measurement sensor for renal stimulation response and renal denervation endpoint assessment

Abstract

Systems and methods for performing a treatment procedure using a treatment device comprising electrodes by applying stimulation signals from the electrodes to a vascular wall; observing a physiological response to the stimulation signal; applying a therapy to the vessel wall; applying another stimulation signal from the electrodes to the blood vessel; and observing a second physiological response to the second stimulation signal. The therapy is successful when the second physiological response differs from the first physiological response by more than a threshold.

Description

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 498,975, filed May 25, 2023, the entire contents of which are incorporated herein by reference. TECHNICAL FIELD

[0002] The present disclosure relates to systems and methods of determining changes in physiological parameters of blood vessels during or caused by a neurostimulation or therapeutic denervation procedure. BACKGROUND

[0003] Catheters have been proposed for use in various medical procedures. For example, a catheter can be configured to deliver neuromodulation (e.g., denervation) therapy to a target tissue site to alter 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 major involuntary bodily control system often 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, over-activation of the renal SNS has been identified in experiments and in humans as a possible cause of the complex pathophysiology of arrhythmia, hypertension, volume overloading states (e.g., heart failure), and progressive kidney 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 a renal denervation procedure, a clinician delivers energy, such as radiofrequency, ultrasound, cooling, or other energy, to a treatment site to reduce the activity of the perivascular nerves. The energy delivered to the treatment site can provide various therapeutic effects by altering sympathetic nerve activity.

[0005] One aspect of current systems is the limited feedback provided to the user that the application of denervation therapy has resulted in a measurable physiological change. Further, the limited feedback makes therapy endpoint determination difficult. Accordingly, the present disclosure relates to systems and methods that address these shortcomings of current technology. SUMMARY

[0006] One aspect of the disclosure relates to a method of evaluating a denervation procedure, the method comprising: outputting, by an interrogator, an interrogator signal comprising a frequency sweep to drive an antenna disposed within a blood vessel prior to application of a therapy at a location of a blood vessel wall; detecting, at the interrogator, a first reflection component of the signal. The method further comprises monitoring, while the therapy is applied at the location of the blood vessel wall, subsequent reflection components of the signal; determining that a change between the subsequent reflection components and the first reflection component exceeds a threshold; and in response to determining that the change between the subsequent reflection components and the first reflection component exceeds the threshold, performing an action. 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 and systems described herein.

[0007] Implementations of the aspect of the disclosure can include one or more of the following features. In the method, performing the action includes at least one of outputting an indication that the change exceeds the threshold or stopping application of the therapy to the location of the blood vessel. The method further includes applying a stimulation signal from an electrode of the therapeutic device to the blood vessel wall. Monitoring the subsequent reflection component of the signal includes observing a response to the stimulation signal in the reflection component of the signal. The stimulation signal causes a contraction of muscle fibers within the blood vessel by stimulating nerves in or near the blood vessel wall, thereby causing a reduction in blood volume within the blood vessel. Monitoring the subsequent reflection component includes continuously monitoring the subsequent reflection component, periodically monitoring the subsequent reflection component, or intermittently monitoring the subsequent reflection component. An increase in a peak magnitude or an increase in a resonant frequency associated with the subsequent reflection component relative to a peak magnitude or a resonant frequency associated with the first reflection component indicates a reduction in blood volume within the blood vessel. The stimulation signal is part of a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol. Monitoring the subsequent reflection component includes periodically monitoring the subsequent reflection component, wherein the analog signal is part of a sequential stimulation protocol or an alternating stimulation protocol, and wherein periodically monitoring the subsequent reflection component occurs during a stimulation portion of the sequential stimulation protocol or the alternating stimulation protocol. The therapy includes at least one of monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation. An increase in blood volume within the blood vessel indicates successful denervation of nerves in or near the location of the blood vessel wall. A decrease in a magnitude or a decrease in a resonant frequency associated with the subsequent reflection component after application of the therapy indicates an increase in blood volume within the blood vessel. The method further includes outputting, by the interrogator, a second interrogator signal including a second frequency sweep to drive a second antenna within the blood vessel, detecting, at the interrogator, a reflection component of the second interrogator signal, and calculating a pulse wave velocity or a pulse transit time of blood within the blood vessel. A change in the pulse wave velocity or the pulse transit time exceeding a threshold indicates an increase in blood volume within the blood vessel. The increase in blood volume within the blood vessel indicates successful denervation of nerves in or near the blood vessel. The blood vessel is one or more of the following or a branch thereof: celiac trunk, hepatic artery, splenic artery, gastric artery, superior mesenteric artery, inferior mesenteric artery, gonadal artery, splanchnic artery. Implementations of the described technology can include hardware, a method or process, or computer software located on a computer-accessible medium, including software installed on a system, firmware, hardware, or combinations of the above that in operation, make the system perform actions. One or more computer programs can be configured to perform particular operations or actions by including instructions for the actions in the programs, which when executed by data processing apparatus, cause the apparatus to perform the actions.

[0008] Another aspect of the present disclosure relates to a therapy system, further comprising: an elongated member configured to navigate within a blood vessel, the elongated member including a proximal portion and a distal portion; a plurality of electrodes formed on the distal portion of the elongated member, the electrodes in electrical communication with a stimulation source; an antenna loop formed on at least one of the electrodes; a sensor loop formed on at least one of the electrodes; and an interrogator in electrical communication with the antenna loop and configured to initiate an interrogator signal comprising a frequency sweep to drive the antenna loop, wherein the interrogator is configured to receive a signal from the sensor loop indicative of a reflected component of the interrogator signal. 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 and systems described herein.

[0009] Implementations of the aspect of the disclosure can include one or more of the following features. In the treatment system, the antenna loop and the sensor loop inductively couple when the antenna loop transmits the interrogator signal. The treatment system further includes a therapy source to deliver a therapy to the location of the vessel wall. The therapy includes at least one of: a monopolar radiofrequency denervation, a bipolar radiofrequency denervation, an ultrasound denervation, a focused ultrasound denervation, a cryogenic denervation, or a chemical denervation. The therapy source is in electrical communication with the electrode to apply the therapy to the location of the vessel wall. The electrode is configured to apply a stimulation signal to the vessel wall. The stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol. The treatment system further includes a computing device including a processor and a memory having an application stored thereon that, when executed by the processor: receives a signal indicative of the reflected component of the interrogator signal; and detects a change in the signal indicative of the reflected component of the interrogator signal. The action includes outputting, to a display device in communication with the computing device, an indication that the change exceeds a threshold or ceasing to apply the therapy to the location of the vessel wall. The application, when executed by the processor, and in response to detecting that the change in the signal indicative of the reflected component of the interrogator signal exceeds a threshold, performs the action. The interrogator is in electrical communication with the second antenna loop and is configured to initiate a second interrogator signal including a second frequency sweep to drive the second antenna, where the interrogator is configured to receive a second signal indicative of a reflected component of the second interrogator signal from the second sensor loop. The treatment system further includes a computing device including a processor and a memory having an application stored thereon that, when executed by the processor: receives a signal indicative of the reflected component of the interrogator signal; receives a signal indicative of the reflected component of the second interrogator signal; and calculates a pulse wave velocity or a pulse transit time of blood within the vessel. Implementations of the described technology can include hardware, a method or process, or computer software located on a computer-accessible medium, including software installed on a system that, in operation, causes the system to perform actions. One or more computer programs can be configured to perform particular operations or actions by including instructions for the actions in the programs, which when executed by data processing apparatus, cause the apparatus to perform the actions.

[0010] Yet another aspect of the disclosure relates to a treatment system comprising: an elongated member configured for intravascular navigation, the elongated member comprising a distal portion and a proximal portion; a plurality of electrodes formed on the distal portion of the elongated member, the electrodes configured to be in electrical communication with a stimulation source; and an ultrasound transducer formed on the elongated member, wherein the ultrasound transducer is configured to detect a signal indicative of a vascular murmur of a 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 and systems described herein.

[0011] Particular implementations of this aspect of the disclosure can include one or more of the following features. The treatment system further includes a therapy source to deliver a therapy to a location of a blood vessel wall. The therapy includes at least one of: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation. The therapy source is in electrical communication with the electrodes to apply the therapy to the location of the blood vessel wall. The electrodes are configured to apply a stimulation signal to the blood vessel wall. The stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol. The treatment system further includes a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor: receives, from the ultrasound transducer, a signal indicative of a vascular murmur of a blood vessel; computes a spectral power from the received signal indicative of the vascular murmur; and detects a change in the spectral power. The application, when executed by the processor and in response to detecting that the change in the spectral power exceeds a threshold, performs an action. The action includes outputting, to a display device in communication with the computing device, an indication that the change exceeds the threshold or ceasing to apply the therapy to the location of the blood vessel wall. Particular implementations of the described technology can include hardware, a method or process, or computer software located on a computer-readable medium such as a diskette, hard drive, or available via a network such as the Internet or WAN, such software including an installation program that installs the software on a system, firmware, hardware, or a combination thereof, the software, firmware, hardware, or combination thereof, when executed, operable to cause a system to perform actions.

[0012] Yet another aspect of the present disclosure relates to a method of evaluating a denervation procedure. The method further includes receiving, by a computing device, a signal indicative of a blood vessel hum of a blood vessel in which an elongated member has been placed, wherein the blood vessel hum is detected by an ultrasound transducer carried by the elongated member; converting, by the computing device, the blood vessel hum to a spectral power; monitoring the spectral power over time as a therapy is applied to a blood vessel wall of the blood vessel in which the elongated member has been placed; determining that a change in the spectral power over time exceeds a threshold; and in response to determining that the change in the spectral power over time exceeds the threshold, performing an action. Other implementations 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 described herein.

[0013] Particular implementations of this aspect of the present disclosure can include one or more of the following features. In the method, performing the action includes at least one of outputting an indication that the change exceeds the threshold or stopping the application of the therapy to the location of the blood vessel. The method further includes applying a stimulation signal from an electrode of a therapeutic device to the blood vessel wall. Monitoring the spectral power includes observing a response in the spectral power to the stimulation signal. An increase in the spectral power is indicative of a decrease in blood volume within the blood vessel. The stimulation signal causes a contraction of muscle fibers within the blood vessel by stimulating nerves in or near the blood vessel wall, thereby causing the decrease in blood volume within the blood vessel. The stimulation signal is part of a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol. Monitoring the spectral power includes continuously monitoring the spectral power, periodically monitoring the spectral power, or periodically monitoring the spectral power. Monitoring the spectral power includes periodically monitoring the spectral power, wherein the stimulation signal is part of a sequential stimulation protocol or an alternating stimulation protocol, and wherein periodically monitoring occurs during a stimulation portion of the sequential stimulation protocol or the alternating stimulation protocol. The therapy includes at least one of monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, and cryogenic denervation or chemical denervation. A decrease in the spectral power after the application of the therapy is indicative of an increase in blood volume within the blood vessel. The increase in blood volume within the blood vessel is indicative of successful denervation of nerves in or near the location of the blood vessel wall. The blood vessel is one or more of the following or a branch thereof: celiac trunk, hepatic artery, splenic artery, gastric artery, superior mesenteric artery, inferior mesenteric artery, gonadal artery, splanchnic artery. Particular implementations of the described techniques can include hardware, methods or processes, or computer software located on one or more computer storage devices, including software installed on a system, firmware, hardware, or combinations thereof, that in operation, make the system execute actions. One or more computer programs can be configured to perform particular operations or actions by including instructions for the actions in the one or more programs, which when executed by data processing apparatus, cause the apparatus to perform the actions.

[0014] Also disclosed herein are systems and methods for performing a treatment procedure with a treatment device comprising electrodes by applying a stimulation signal from the electrodes to a blood vessel wall, observing a physiological response to the stimulation signal, applying a therapy to the blood vessel wall, applying another stimulation signal from the electrodes to the blood vessel, and observing a second physiological response to the second stimulation signal. When the second physiological response differs from the first physiological response by more than a threshold value, the therapy is successful. BRIEF DESCRIPTION OF DRAWINGS

[0015] Various aspects and embodiments of the present disclosure are described hereinafter with reference to the drawings, in which:

[0016] Figure 1 is a schematic illustration of a therapy system according to the present disclosure;

[0017] Figure 2 is Figure 1 a schematic illustration of a workstation of the therapy system of

[0018] Figure 3 is a perspective view of a treatment device according to the present disclosure Figure 1 advancing within a portion of a patient's anatomy and in a deployed state of the therapy system of

[0019] Figure 4A is a schematic illustration of an electrode according to the present disclosure;

[0020] Figure 4B is a plot representing the change in S11 in response to a change in the volume of a fluid;

[0021] Figure 5A is a flowchart detailing a method according to the present disclosure;

[0022] Figure 5B is a plot depicting the change in resonant frequency and S11 magnitude through a cardiac cycle;

[0023] Figure 5C is a plot of S11 as a function of time at a given resonant frequency;

[0024] Figure 6A is a perspective view of a treatment device according to the present disclosure;

[0025] Figure 6B is a cross-sectional view of an ultrasound transducer on a catheter according to the present disclosure Figure 6A of the therapy system of

[0026] Figure 7 is a flowchart of a method according to the present disclosure;

[0027] Figure 8Ais a plot of a carotid artery murmur under high blood pressure, and a plot of the carotid artery murmur to spectral power conversion; and

[0028] Figure 8B is a plot of a carotid artery murmur under low blood pressure, and a plot of the carotid artery murmur to spectral power conversion. DETAILED DESCRIPTION

[0029] The present disclosure relates to therapeutic systems and methods for sympathetic or parasympathetic nerve stimulation or treatment denervation or neuromodulation, particularly of the unmyelinated nerve fibers in and around vascular and other luminal tissue. In particular, the present disclosure relates to systems and methods that provide feedback of physiological responses to the application of nerve stimulation prior to, during, or after therapeutic denervation.

[0030] According to one aspect of the present disclosure, a signal generator or vector network analyzer (VNA) is employed to power an antenna formed on or carried by a catheter. The antenna emits an RF signal that inductively couples with a passive sensor. The passive sensor is also formed on or carried by the catheter. The signal generator or VNA receives a reflected component of the signal emitted by the antenna via the passive sensor, i.e., the S11 component. The reflected component varies based on the dielectric constant of the medium through which the antenna is attempting to transmit. By analyzing the reflected component, i.e., the S11 component, a determination of the volume of the medium can be assessed. This determination of a change in volume of the medium, e.g., blood flowing through a blood vessel, can be assessed to determine, among other things, a constriction of the blood vessel, e.g., due to an applied stimulus, which reduces the volume of blood in the blood vessel. The S11 component, and the volume of the blood vessel thereof, can also help identify a treatment endpoint, such as complete denervation of a nerve, which typically results in an increase in volume in the blood vessel. The S11 component can also be used to calculate features of the blood flow, including pulse wave velocity or pulse transit time, which itself provides information of a change in volume of the blood vessel, e.g., as a result of denervation.

[0031] Another aspect of the present disclosure relates to a catheter incorporating a piezoelectric film to detect a blood vessel murmur. The blood vessel murmur is a sound of the blood vessel caused in part by turbulent flow of the blood. The piezoelectric film acts as an internal stethoscope (piezoelectric microphone) that detects the turbulent flow of the blood on the piezoelectric film. As the blood flows over the piezoelectric film, the piezoelectric film generates a signal in response to the turbulent flow of the blood impacting the piezoelectric film. This signal, i.e., the blood vessel murmur, varies with blood pressure and the volume of blood flowing through the blood vessel. Thus, by detecting changes in the blood vessel murmur, the blood pressure can be determined, and from that the volume of blood flowing through the blood vessel. In this way, changes in blood pressure and blood flow caused by stimulation or denervation can be assessed for various purposes. These and other aspects of the present disclosure are described in greater detail below.

[0032] For ease of description, much of the following description focuses on specific implementations of electrical stimulation and radiofrequency (RF) denervation. Those skilled in the art will recognize that the methods and systems described herein can employ any of the therapy modalities and / or nerve stimulation modalities described herein, including but not limited to monopolar RF, bipolar RF, microwave, ultrasound, focused ultrasound, cryogenic, chemical, etc. Similarly, the following description focuses on navigating to a renal artery and applying therapy to the renal artery to denervate sympathetic or, in certain embodiments, parasympathetic nerves in, around, and near the renal artery. However, the present disclosure is not so limited, and can be used to denervate nerves accessible via any blood vessel (e.g., celiac trunk, hepatic, splenic, gastric, superior mesenteric, inferior mesenteric, gonadal, splanchnic, etc., as well as branches and / or combinations of each) or other luminal tissue (e.g., bile duct, urethra, etc.) described herein.

[0033] Turning now to the drawings, Figure 1 A guidance and therapy system in accordance with the present disclosure is shown and generally identified by reference numeral 10. As will be described in further detail below, guidance and therapy system 10 enables navigation of a treatment device 50 to a desired location within a patient's anatomy (e.g., a patient's renal artery). Treatment device 50 is configured to apply nerve stimulation (e.g., to a blood vessel wall) to trigger a nerve response (e.g., vasoconstriction or a temporary increase in blood pressure), and to apply a denervation therapy to denervate nerves within and around a blood vessel to treat one or more conditions. The treatment device is also configured to deliver interrogation signals to assess blood flow parameters, to provide data regarding the effects of the nerve stimulation and denervation therapy, e.g., to determine endpoints for the denervation therapy and / or the patient's response to the denervation therapy.

[0034] Guidance and therapy system 10 includes a workstation 20, a treatment device 50 operably coupled to the workstation 20, and an imaging device 70, which can be operably coupled to the workstation 20. A patient "P" is shown lying on an operating table 12, with treatment device 50 inserted through a portion of the patient's femoral artery, although it is contemplated that treatment device 50 can be inserted into any suitable portion of the patient's vasculature in fluid communication with a desired blood vessel for therapy. Although generally described as having one treatment device 50, it is envisioned that therapy system 10 can employ any suitable number of treatment devices 50. Treatment devices 50 can employ the same or different therapy modalities, and can be operably coupled to workstation 20. Further, treatment devices 50 can employ a guidewire or guide catheter 58 (not shown) Figure 3 ) without departing from the scope of the present disclosure. In some examples, treatment device 50 can not be coupled to workstation 20, e.g., where therapy is applied via a cryogenic or chemical ablation procedure.

[0035] continue Figure 1 And refer to other sources Figure 2 Workstation 20 includes computer 22, a therapy source 24 (e.g., RF generator, microwave generator, ultrasound generator, cryogenic medium source, chemical source, etc.) operatively coupled to computer 22, and a stimulation source 24a operatively coupled to computer 22. Although typically described as separate from therapy source 24, it is envisioned that interrogation signal source 24a may be integrated within therapy source 24, and therapy source 24 may generate both therapy modalities and stimulation modalities.

[0036] As will be understood, in some cases, the therapy source 24 or the interrogation signal source 24a may be detached from the workstation 20, but still controlled by the workstation 20 (e.g., via Bluetooth). ® (e.g., wireless communication protocols). Furthermore, in cases where, for example, the treatment device 50 is configured to apply cryotherapy or chemical ablation, the workstation may not have connection or control to the therapy source 24 and the interrogation signal source 24a. In this case, the interrogation signal source 24a may be integrated into the handle of the treatment device 50, or as a separate device inserted into the patient's blood vessel and used as described elsewhere herein.

[0037] The computer 22 is coupled to a display 26 configured to display one or more user interfaces 28. The computer 22 may be a desktop computer or a tower configuration with a display 26, or it may be a laptop computer or other computing device. The computer 22 includes a processor 30 that executes software stored in memory 32. Memory 32 may store one or more application programs 34 and / or algorithms 44 to be executed by the processor 30. A network interface 36 enables the workstation 20 to communicate with various 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. Alternatively or additionally, communication may be via self-organizing Bluetooth, enabling communication with wide area networks (WANs) and / or local area networks (LANs). ®or wireless network. The network interface 36 can connect to the Internet via one or more gateways, routers, and network address translation (NAT) devices. The network interface 36 can communicate with a cloud storage system 38 in which additional data, image data, and / or video can be stored. The cloud storage system 38 can be remote from the hospital or in the hospital building, such as in a control or hospital information technology room. It is contemplated that the cloud storage system 38 can also serve as a host for more robust analysis of acquired images (e.g., fluoroscopy, computed tomography (CT), magnetic resonance imaging (MRI), cone beam computed tomography (CBCT), etc.), data, etc. (e.g., additional or enhanced data for analysis and / or comparison). The input module 40 receives input from input devices such as a keyboard, mouse, voice commands, energy source controls (e.g., foot pedals or hand-held remote control devices that enable the clinician to activate, terminate therapy source 24 and / or stimulation source 24a and, optionally, adjust various operating characteristics of the therapy source and / or the stimulation source, including but not limited to power delivery), etc. The output module 42 connects the processor 30 and memory 32 to various output devices such as the display 26. In embodiments, the display screen 26 can be a touch screen display.

[0038] The therapy source 24 generates and / or outputs one or more of RF energy (monopolar or bipolar), microwave energy, ultrasound energy, cryogenic media, or chemical ablation media via automatic control algorithms 44 stored on the memory 32 and / or under the control of the clinician. As can be appreciated, the therapy generated and / or output by the therapy source 24 can change the temperature of tissue (e.g., raise or lower the temperature) to achieve a desired denervation of a nerve or otherwise affect the nerve tissue to inhibit or terminate nerve function. The therapy source 24 can be configured to produce and / or output energy and / or therapy of a selected modality and magnitude for delivery to a treatment site via the treatment device 50, as will be described in further detail below. In examples where the therapy source 24 outputs electrical energy, the therapy source 24 can monitor the voltage and current applied to the target tissue via the treatment device 50 and monitor the temperature of the target tissue or tissue proximate to the target tissue and / or a portion of the treatment device 50. The treatment device 50 or therapy source 24 can also measure and monitor the impedance of the tissue through which therapy or guide energy is transmitted to provide an indication of the state of the tissue.

[0039] The stimulation source 24a generates stimulation signals, such as biphasic waveforms at energy levels below the therapeutic energy levels (i.e., denervation energy levels) generated by the therapy source 24, such that the stimulation generated by the stimulation source 24a does not denervate the target tissue. Rather, the stimulation source 24a generates stimulation signals that are capable of effecting a response from the nerves adjacent to the therapeutic element of the therapy device 50. The response can include an increase in blood pressure, an increase in vessel stiffness, a change in vessel diameter (vessel constriction), a change in pulse wave velocity, an increase in pressure, a change in heart rate, etc., and combinations of these.

[0040] The amplitude, frequency, pulse width, and / or duration of the nerve stimulation can be selected and / or modified to ensure stimulation of the sympathetic nerves of the luminal tissue without damaging the luminal tissue or nerves within or surrounding the luminal tissue or causing excessive vasoconstriction around the therapy device (e.g., inhibiting movement of the therapy device within the luminal tissue). The pulse duration (pulse width) can be modified to ensure that anodal stimulation of the tissue is maintained, as at certain pulse durations, the area of anodal stimulation can dissipate or otherwise disappear, resulting in a reduced stimulation effect. In one non-limiting embodiment, the stimulation source 24a generates biphasic waveforms having a frequency between about 10 Hz and 30 Hz, a voltage between about 5 V and 30 V, a current between about 2 mA and 500 mA, and a pulse width between about 2 ms and 10 ms. It is contemplated that in embodiments targeting unmyelinated nerve fibers, the pulse width of the biphasic waveforms can be between about 2 ms and 120 ms. In another example, the stimulation parameters are a constant current of 20 mA for the vessel branches and a constant current of 30 mA for the main vessel, a pulse width of 5 mS, a frequency of about 20 Hz, and a duration between 10 seconds and 60 seconds.

[0041] Another aspect of the present disclosure, described in greater detail below, is an interrogator 64 (e.g., a vector network analyzer) that can be incorporated into the workstation 20 and used to detect changes in the capacitance of the blood vessel to be treated. The signals detected by the interrogator 64 and their significance with respect to the blood volume within the blood vessel can be presented on the display 26 (e.g., the end point of the vessel constriction and the application of therapy).

[0042] Figure 3One embodiment of a treatment device 50 according to the present disclosure is depicted. The treatment device 50 includes an elongated shaft 52 having a handle (not shown) disposed on a proximal end portion of the elongated shaft 52. The treatment device 50 includes an energy delivery assembly 54 at which one or more therapy electrodes 56 are located. The elongated shaft 52 of the treatment device 50 is configured to be advanced within a portion of a patient’s vasculature, such as a femoral artery or other suitable portion of a patient’s vasculature in fluid communication with a patient’s renal artery. In embodiments, the energy delivery assembly 54 is configured to transition from an initial, un-deployed configuration having a generally linear profile into a second, deployed or expanded configuration in which the energy delivery assembly 54 forms a generally helical and / or spiral configuration for delivering energy to a treatment site in order to apply one or both of a stimulation signal or a treatment energy at the treatment site. Those skilled in the art will recognize that, in the context of the present application, the application of treatment energy should be interpreted to include the application of cryogenic cooling to the treatment site to effect thermal-induced neuromodulation as well as the application of chemical denervation methods. In this manner, when in the second expanded configuration, the energy delivery assembly 54, and in particular the individual electrodes 56, press against or otherwise contact a wall of a patient’s vasculature tissue. Although generally described as transitioning into a helical and / or spiral configuration, it is envisioned that the energy delivery assembly 54 can be deployed in other configurations without departing from the scope of the present disclosure. Additionally, the treatment device 50 can be configurable, e.g., using one or more pull wires (not shown) to adjust the configuration to facilitate contact between the electrodes 56 and a wall of a renal artery. As such, the treatment device 50 can be capable of being placed in one, two, three, four, or more different configurations depending on the design requirements of the treatment device 50 or the location at which therapy is to be applied.

[0043] As Figure 3 depicted, the elongated shaft 52 can be configured to be received within a portion of a guide catheter or sheath, such as a 6F guide catheter 58, which is used to navigate the treatment device 50 to a desired location, at which point the guide catheter 58 is retracted to reveal the treatment device 50. As noted above, the retraction of the guide catheter 58 can enable the energy delivery assembly 54 to transition from the first, un-deployed configuration into the second, deployed or expanded configuration.

[0044] The elongated shaft 52 of the treatment device 50 can further include an aperture (not shown) at a distal end thereof that is configured to slidably receive a guidewire over which the treatment device 50 is advanced, either alone or in combination with the guide catheter 58. In this manner, the treatment device 50 is guided to the target tissue using an over-the-wire (OTW) or rapid exchange (RX) technique with a guidewire, at which point the guidewire can be partially or completely removed from the treatment device 50 such that the treatment device 50 is capable of transitioning from the first, un-deployed configuration into the second, deployed or expanded configuration Figure 3). As described elsewhere herein, the treatment device 50 can transition from the first, unexpanded configuration to the second, expanded configuration automatically (e.g., via shape memory alloy, etc.) or manually (e.g., via pull wires, guidewire manipulation, etc. controlled by a clinician).

[0045] With continued reference to Figure 3 In embodiments where the treatment device 50 is an RF ablation catheter, the energy delivery assembly 54 includes one or more electrodes 56 disposed on an outer surface thereof that are configured to contact a portion of the patient’s vasculature when the treatment device 50 is placed in the second, expanded configuration. As shown herein, the treatment device 50 includes four electrodes 56. However, the present disclosure is not so limited and the treatment device 50 can have more or fewer electrodes 56 without departing from the scope of the present disclosure. Those skilled in the art will recognize that one or more of the electrodes 56 can be replaced with ultrasound transducers, microwave antennae, ports for delivering cryoablation media or chemical media, and other instruments and / or ablation and denervation modalities without departing from the scope of the present disclosure.

[0046] As shown, the electrodes 56 are disposed in spaced apart relation to one another along the length of the treatment device 50, thereby forming the energy delivery assembly 54. As will be appreciated, these electrodes 56 are in communication with both the therapy source 24 and the stimulation source 24a. In one example, the therapy source 24 generates monopolar RF energy to denervate sympathetic nerves of the associated blood vessel. The electrodes 56 can deliver RF energy independently of one another (e.g., monopolar), simultaneously, selectively, sequentially, and / or between any desired combination of the electrodes 56 (e.g., bipolar). It is contemplated that, in one embodiment, the therapy source 24 is also the stimulation source 24a and includes a diagnostic mode in which the therapy source 24 generates neural stimulation having a frequency of 10-1000 Hz and a denervation mode in which the therapy source 24 generates RF energy to denervate nerves of the associated blood vessel. It is contemplated that the therapy source 24 can be manually switched from the stimulation mode to the denervation mode and vice versa, or can be automatically switched by the algorithm 44 stored on the memory 32 of the computing device. Alternatively, the electrodes 56 are in communication with a separate stimulation source 24a to deliver a stimulation signal to the blood vessel in question. The stimulation signal (e.g., a biphasic waveform) is generated by the stimulation source 24a and delivered to the electrodes 56, thereby causing stimulation of the sympathetic nerves as described herein. Application of the stimulation can effect one of a variety of physiological responses, including an increase in systolic pressure, an increase in mean arterial blood pressure, an increase in vascular stiffness, a change in blood vessel diameter (e.g., vasoconstriction), an increase in pulse wave velocity, an increase in pulse duration, an increase in vascular stiffness, and combinations of these and other responses.

[0047] While the electrodes 56 are described herein as having both therapy and stimulation capabilities, the present disclosure is not so limited. For example, the therapy device 50 can include one or more electrodes 56 configured to deliver therapy (rather than stimulation) and one or more electrodes 56 configured to deliver stimulation (rather than therapy).

[0048] According to another aspect of the present disclosure as Figure 4A According to another aspect of the present disclosure as

[0049] In practice, the interrogator 64 generates a frequency sweep (e.g., from approximately 1 MHz to 5 MHz) signal such that the antenna loop 60 resonates and emits an RF signal to inductively couple with the sensor loop 62. Those skilled in the art will appreciate that the RF signal is a non-therapeutic RF signal. However, based in part on the dielectric constant of the medium through which the output of the antenna loop 60 is to pass, a portion of the signal generated by the interrogator 64 will not be emitted by the antenna 60. This portion of the signal from the interrogator 64 is reflected back to the interrogator 64 via the antenna 60. This reflected component of the signal from the interrogator 64 is calculated as the S11 component of the signal. The antenna 60 can be designed to resonate and emit an RF signal at a particular frequency at which the magnitude S11 component is minimal, thus at which frequency substantially all of the signal generated by the interrogator 64 is emitted by the antenna.

[0050] As will be appreciated, the magnitude and minimum amplitude frequency of the S11 component or reflected signal varies based on the dielectric constant of the medium through which the RF signal will be transmitted. Relatedly, when the medium fluid properties remain constant, the dielectric constant also varies with changes in the medium volume, and as Figure 4BAs shown, the frequency of the S11 component also changes. Thus, as the capacity of the medium changes, the magnitude and frequency of the S11 component also change. Thus, by analyzing the S11 component and finding the frequency at which it has its minimum amplitude, the capacity changes of the medium can be detected. As described in more detail below, these capacity changes can be analyzed to detect vasoconstriction in response to the stimulus, and to detect an effective denervation signal that stops the therapy application at the appropriate time.

[0051] Figure 5A The method 500 depicted utilizes a therapy device 50 that employs an antenna 60 and a sensor 62 to detect vasoconstriction and an end point of therapy application. There are several protocols for stimulating the nerves of the blood vessels (e.g., the sympathetic nerves of the renal artery). These stimulation protocols include a sequential stimulation in which a stimulus is applied for a duration of time, followed by application of therapy for a duration of time, and ending the application of the stimulus. For example, an initial stimulus can be applied to the tissue to achieve a response between 5 seconds and 60 seconds, in some aspects about 10 seconds, followed by application of therapy for a duration between 20 seconds and 60 seconds, in some aspects about 40 seconds, followed by further stimulation between 5 seconds and 20 seconds, in some aspects about 10 seconds.

[0052] A second stimulation protocol is an alternating stimulation protocol. In the alternating protocol, a series of short duration stimulation signals (e.g., between 5 ms and 20 ms, in some aspects about 10 ms) are applied, followed by therapy for between 20 ms and 60 ms (in some aspects about 40 ms). For example, this pattern of 10 ms of stimulation followed by 40 ms of therapy is repeated throughout a duration (e.g., between 30 seconds and 120 seconds, in some aspects about 60 seconds).

[0053] Yet another stimulation protocol is a simultaneous protocol in which a stimulus is applied for a short duration (e.g., 5 ms to 20 ms, up to 1 s to 5 s) before therapy is applied. The stimulus and therapy are applied until a change in a physiological parameter is detected or until an energy application threshold (e.g., duration, tissue temperature, amount of energy) is reached. In the absence of detecting a change in the measured parameter or a change in response to the stimulus, the process can be repeated. During the short duration in which only the stimulus is applied, it can be determined whether a response is detected, and if no response is detected, the application of denervation energy can be stopped or prevented, and one or more indicators can be presented to the user that the placement of the therapy device 50 should be adjusted, or that the previous therapy application has been successful.

[0054] According to the present disclosure, as Figure 4BAs shown, the decrease in the magnitude of the S11 component or the frequency of the minimum amplitude is associated with an increase in the capacity of the medium (e.g., the capacity of the blood vessel) through which the antenna 60 is transmitting. As generally understood, a person with high blood pressure often experiences a reduction in the diameter of certain blood vessels (e.g., the kidneys, liver, or others). The reduction in diameter necessarily results in a reduction in the blood volume flowing through the blood vessel as a result of the muscular contraction within the blood vessel caused by neural activity (overactive sympathetic nerves). However, further stimulation (e.g., electrical or focused ultrasound) generally results in further contraction and reduction in diameter of the blood vessel. Thus, by sensing the changes in the S11 component, the efficacy of the stimulation (e.g., proper placement of the treatment device) can be assessed. Denervation severs the pathway for neuronal activity through the sympathetic nerves, allowing the muscle to relax and with it an increase in the diameter of the blood vessel. Thus, as described herein, analysis of the S11 component can be used to assess the progress of the denervation procedure and identify whether the denervation has been successful and provide an indication of the endpoint of the application of the therapeutic energy.

[0055] With respect to the method 500, at step 502, the treatment device 50 is navigated to a location in a blood vessel for denervation. Once placed within a blood vessel (e.g., a renal or hepatic artery), the interrogator 64 can initiate a frequency sweep (e.g., from about 1 GHz to about 5 GHz) at step 504 to resonate and transmit the antenna. With the transmission of step 504, an initial S11 value is determined at step 506. At step 508, stimulation is initialized from the stimulation source 24a and applied to the tissue via the electrodes 56. Regardless of the stimulation protocol employed, at step 510, it is determined whether any reaction to the stimulation is detected. In accordance with the present disclosure, the reaction can be a shift in the magnitude of the detected S11 component or the frequency of the minimum amplitude, signaling a change in the diameter of the blood vessel due to the application of the stimulation and necessarily with it a change in the blood volume in the blood vessel. If no reaction to the stimulation is detected at step 510, the method 500 returns to step 502 for replacement of the treatment device 50 within the blood vessel.

[0056] In embodiments in which the S11 component is detected by the interrogator 64, and in accordance with Figure 4B Effective stimulation of the nerves within or near the blood vessel results in a change in the capacity of the blood vessel (blood vessel contraction), which is observable based on the magnitude of the detected S11 component and the change in the frequency of the S11 component observed. Stimulating the nerves of the blood vessel to cause blood vessel contraction results in an increase in both the magnitude and the frequency of the S11 component.

[0057] At step 512, the therapy is initialized, which can employ any stimulation protocol, and thus any related therapy, as described above. The therapy can be the application of an RF monopolar signal to the tissue of the blood vessel via the electrode 56. With the therapy initialized, at step 514, the S11 component can be monitored continuously, periodically, or intermittently by the interrogator 64. As an example, the periodicity can be defined by the application of stimulation (e.g., evaluation only after each stimulation). In an example, after each application of stimulation, the S11 component can be analyzed at step 514 as described above, and a change in the S11 magnitude or frequency compared to step 506 can be evaluated at step 516 to exceed a threshold. If the threshold has not been reached, at step 518, a query is made whether the therapy duration or energy application limit has been reached, and if not, the method returns to step 512 for additional or continued application of therapy. Alternatively, the S11 component can be continuously analyzed at step 514, including during the application of therapy at step 512, and when a change in S11 is detected that exceeds a threshold, the application of therapy is stopped at step 516. In either case, the change in S11 is used to determine the endpoint of the therapy, and provide an indication to the user that the therapy has been successful. Conversely, if the therapy duration or energy limit is reached at step 518 without detecting a change greater than the threshold, the method is stopped.

[0058] As an alternative or supplement to the above-described system and method of utilizing the S11 component as an indicator of blood vessel constriction and as an endpoint for the application of treatment energy for denervation, the S11 component can be continuously monitored and correlated with other blood flow parameters. Pulse wave velocity (PWV) is the speed at which a pressure pulse of blood travels through an artery, such as the renal or hepatic artery. A related parameter is pulse transit time, which refers to the time it takes for a pulse wave to travel between two points along an artery. As will be appreciated, the velocity is equal to the distance between the two points divided by the time between the two points.

[0059] Figure 5B The change in the resonant frequency (or frequency of the minimum amplitude) of the S11 component is depicted in both the systolic and diastolic phases of the heartbeat. As described above, this change in the resonant frequency is based at least in part on changes in the dielectric constant as the blood volume in the artery changes. The frequency and magnitude of the minimum amplitude of S11 can be tracked and analyzed throughout the cardiac cycle. As will be appreciated, once the therapy device 50 is placed within the blood vessel, the changes in blood volume within the blood vessel vary on a consistent basis throughout the cardiac cycle without stimulation (from the therapy device 50 or other source) or application of treatment denervation energy. Thus, Figure 5B The curve in S11 is related to the pressure wave of blood flowing through the blood vessel in question. S11 tracks the heart contraction and heart relaxation of the pressure wave, as the flow and volume changes during these cardiac relaxation and cardiac contraction periods.

[0060] Figure 5C A plot is depicted of the magnitude of S11 (measured in decibels - dB) as a function of time at a given resonant frequency. In Figure 5C , the resonant frequency in question is approximately 3.21 MHz, which is generally consistent with the peak resonant frequency observed in Figure 5B . However, the value of the peak resonant frequency can be determined on an individual basis for each patient. As can be seen in Figure 5C , the magnitude of the S11 component as a function of time at the resonant frequency. The increasing curve (1) substantially corresponds to the systolic phase, with increasing values until a peak magnitude is reached, and the decreasing curve (2) substantially corresponds to the diastolic phase.

[0061] According to one aspect of the present disclosure, the treatment device 50 includes at least two electrodes 56, each including an antenna 60 and a sensor 62, with each connected to an interrogator 64. The distance between the electrodes 56 along the length of the blood vessel in which the antenna 60 resides is known. By comparing Figure 5C the plots, the time between the peak magnitudes of each sensor 56 (i.e., the pulse transit time) can be determined. By dividing the distance between the sensors 56 by the pulse transit time, the velocity of blood flow in the blood vessel (PWV) can be calculated. As will be appreciated, by denervating the efferent sympathetic nerves in and around the blood vessel, the nerves cease to stimulate the muscle fibers of the blood vessel. As a result, the muscle fibers relax and the stiffness of the blood vessel decreases. As the stiffness of the blood vessel decreases, the pulse transit time increases and the PWV through the blood vessel decreases. These changes in the pulse transit time and PWV can be used alone or in conjunction with the S11 changes (e.g., as in the method 500) to determine an endpoint of the application of the treatment energy or to confirm successful denervation of the blood vessel. Thus, in one aspect of the present disclosure, along with detecting the initial S11 component value at step 506, an initial pulse transit time or PWV can be calculated. After the denervation therapy is applied, a second pulse transit time or PWV value can be calculated. Upon confirmation that the denervation was successful, a decrease in the PWV or an increase in the pulse transit time beyond a threshold value can be considered. This change can be an absolute value based on empirically collected data, can be a percentage value change, or some other threshold value for confirming the efficacy of the denervation. As will be appreciated, if the change beyond the desired threshold is not achieved, the method can return to step 512 to continue the application of the treatment energy to complete the denervation.

[0062] Yet another aspect of the present disclosure relates to Figure 6A the treatment device 50 depicted. As with the aspect shown in Figure 3 , the treatment device 50 includes a plurality of electrodes 56. In addition, the treatment device 50 includes one or more ultrasound transducers 66. As Figure 6AAs shown, the ultrasound transducer 66 is located proximal to the electrode 56. According to the present disclosure as shown in Figure 6B According to one aspect of the present disclosure as shown, the ultrasound transducer 66 is formed of a polyvinylidene fluoride (PVDF) film 68 secured to the elongated shaft 52, for example, via an epoxy coating 70. Unshown leads can electrically connect the ultrasound transducer 66 to the workstation 20.

[0063] A vascular bruit is a vascular sound typically observed with a stethoscope placed over the carotid artery. When there is blood flow through a stenotic region (i.e., a region of constriction), the stenotic region causes turbulent flow that is different from normal flow in the blood vessel and is observable. The vascular bruit varies depending on the patient's blood pressure, blood flow volume, and area of the stenosis. As Figure 6A The treatment device 50 depicted employing the ultrasound transducer 66 is in effect an ultrasonic stethoscope placed within the blood vessel and capable of listening to the blood flow through the blood vessel.

[0064] According to the method 700 depicted in Figure 7 At step 702, the treatment device 50 is placed or repositioned within the desired blood vessel. Once positioned, the treatment device 50 creates a stenotic region within the blood vessel. The observed sound resulting from the placement of the treatment device 50 can take a period of time to stabilize, but once properly placed, will generally be consistent. At step 704, the initial vascular bruit is detected by listening to the blood flow over the ultrasound transducer 66. The effect of the flow of blood on the ultrasound transducer 66, particularly on the systolic pressure wave, causes the ultrasound transducer 66 to output an electrical signal that can be analyzed by the application program 34 executed by the computer 22. At step 706, the application program 34 can convert the electrical signal generated by the ultrasound transducer 66 into a spectral power. Figure 8A A vascular bruit (blood flow sound) of a blood vessel under high blood pressure is depicted, for example, caused by overactive sympathetic nerves stimulating muscle fibers within the blood vessel or as a result of the stimulus causing constriction of the blood vessel. As can be seen, Figure 8A The spectral power in the Figure 8A spectral power signal of

[0065] At step 708, stimulation can optionally be applied, and in the event that no response is detected at step 710, the method can return to step 702 to adjust placement of the treatment device 50. Alternatively, the method 700 can proceed to step 712, at which treatment energy (e.g., monopolar RF) is applied to the wall of the blood vessel. As with method 500, periodic or continuous monitoring of the spectral power can be performed at step 714. As with method 500, this can be associated with the stimulation protocol employed. In addition, periodic or continuous monitoring of the spectral power can also be performed. At step 716, it is determined whether an opportunity for the spectral power to be greater than a threshold has been achieved. If yes at step 716, the method stops. If a change of less than a threshold is made, the method proceeds to step 718 to determine whether a treatment duration or energy limit has been reached, and if so, the method ends, but if not, the method returns to step 712 to continue therapy.

[0066] Figure 8B Both the sound measured by the ultrasound transducer 66 and the spectral power of that sound for patients with normal or low blood pressure are depicted. The absolute value of the lower spectral power can be different for each individual patient, and the comparison or threshold can be a percentage change (e.g., a 25% change can indicate successful denervation resulting in low or normalized blood pressure) in the spectral power measurement at step 706 and the observation at step 714. Additionally or alternatively, the methods described herein can be used to detect changes in the blood vessel murmur after stimulation is applied to achieve vessel constriction. As the blood vessel constricts (e.g., due to the application of stimulation to the electrodes 56), the blood vessel murmur will be more sharp (e.g., similar to Figure 8A ), and as the blood vessel constriction eases, the blood vessel murmur will be more relaxed (e.g., similar to Figure 8B ).

[0067] According to aspects of the present disclosure, the treatment device 50 can be navigated within a blood vessel or luminal tissue in one configuration (e.g., a linear configuration), and once positioned at a desired location, be deployed or otherwise actuated to achieve a second configuration. Further, although the present disclosure focuses in part on S11 detection or blood vessel murmur, the present disclosure is not so limited, and one or more of changes in pulse width velocity, observed blood vessel diameter (e.g., via fluoroscopy or ultrasound imaging), etc. can be employed alone or in combination with other responses to stimulation and denervation without departing from the scope of the present disclosure.

[0068] Although generally described above, it is contemplated that the memory 32 can include any non-transitory computer-readable storage medium for storing data and / or software including instructions that are executable by the processor 30 and control operation of the workstation 20, and in some embodiments, also control operation of the therapy device 50. In embodiments, the memory 32 can include one or more storage devices, such 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 can include one or more mass storage devices connected to the processor 30 by a mass storage controller (not shown) and a communication bus (not shown).

[0069] Although the description of computer-readable media contained herein refers to solid state storage devices, those skilled in the art will appreciate that computer-readable storage media can be any available media that can be accessed by the processor 30. That is, computer-readable storage media can include non-transitory, volatile and non-volatile, removable and non-removable 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 can include RAM, ROM, EPROM, EEPROM, flash memory or other solid state memory technology, CD-ROM, DVD, Blu-ray or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and that the workstation 20 can access.

[0070] While several embodiments of the disclosure have been shown in the drawings, it is not intended that the disclosure be limited to the embodiments so illustrated, but it is intended that the disclosure have the widest possible scope in accordance with the principles thereof and the following claims. Thus, the above description should not be interpreted as a restriction on the scope or functionality of the disclosure. Those skilled in the art will readily recognize a variety of modifications and alterations of the embodiments described herein, some of which have been described above while others are intended to be within the scope of the claims. Hence, all such modifications and alterations are intended to be within the scope of the claims.

[0071] Example 1. A method of evaluating a denervation procedure, the method comprising: prior to applying a therapy at a location of a blood vessel wall: outputting, by an interrogator, an interrogator signal comprising a frequency sweep to drive an antenna disposed within the blood vessel; detecting, at the interrogator, a first reflection component of the signal; and while applying the therapy at the location of the blood vessel wall: monitoring subsequent reflection components of the signal; determining that a change between the subsequent reflection components and the first reflection component exceeds a threshold; and in response to determining that the change between the subsequent reflection components and the first reflection component exceeds the threshold, performing an action.

[0072] Example 2. The method of example 1, wherein performing the action comprises at least one of: outputting an indication that the change exceeds the threshold or ceasing to apply the therapy to the location of the blood vessel.

[0073] Example 3. The method of example 1, further comprising: applying a stimulation signal from an electrode of a therapeutic device to the blood vessel wall.

[0074] Example 4. The method of example 3, wherein monitoring the subsequent reflection component of the signal comprises: observing a response to the stimulation signal in the reflection component of the signal.

[0075] Example 5. The method of example 3, wherein an increase in a peak magnitude or an increase in a resonant frequency associated with the subsequent reflection component relative to a peak magnitude or a resonant frequency associated with the first reflection component indicates a decrease in blood volume within the blood vessel.

[0076] Example 6. The method of example 4, wherein the stimulation signal causes a decrease in blood volume within the blood vessel by stimulating nerves within or proximate to the blood vessel wall, thereby causing contraction of muscle fibers in the blood vessel.

[0077] Example 7. The method of example 5, wherein the stimulation signal is part of a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

[0078] Example 8. The method of example 6, wherein monitoring the subsequent reflection component comprises: continuously monitoring the subsequent reflection component, periodically monitoring the subsequent reflection component, or intermittently monitoring the subsequent reflection component.

[0079] Example 9. The method of example 7, wherein monitoring the subsequent reflection component comprises: periodically monitoring the subsequent reflection component, wherein the analog signal is part of the sequential stimulation protocol or the alternating stimulation protocol, and wherein periodically monitoring the subsequent reflection component occurs during a stimulation portion of the sequential stimulation protocol or the alternating stimulation protocol.

[0080] Example 10. The method of example 1, wherein the therapy comprises at least one of: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation.

[0081] Example 11. The method of example 1, wherein a decrease in a magnitude or a decrease in a resonant frequency associated with the subsequent reflection component after applying the therapy indicates an increase in blood volume within the blood vessel.

[0082] Example 12. The method of Example 10, wherein the increase in blood volume within the blood vessel indicates successful denervation of nerves in or near the location of the blood vessel wall.

[0083] Example 13. The method of Example 1, further comprising: outputting, by the interrogator, a second interrogator signal comprising a second frequency sweep to drive a second antenna within the blood vessel; detecting, at the interrogator, a reflected component of the second interrogator signal; and calculating a pulse wave velocity or pulse transit time of blood within the blood vessel.

[0084] Example 14. The method of Example 13, further comprising: detecting a change in pulse wave velocity or pulse transit time that exceeds a threshold, wherein the change in pulse wave velocity or the pulse transit time that exceeds the threshold indicates an increase in blood volume within the blood vessel.

[0085] Example 15. The method of Example 14, wherein the increase in blood volume within the blood vessel indicates successful denervation of nerves in or near the blood vessel.

[0086] Example 16. The method of Example 1, wherein the blood vessel is one or more of the following or a branch thereof: celiac trunk, hepatic artery, splenic artery, gastric artery, superior mesenteric artery, inferior mesenteric artery, gonadal artery, splanchnic artery.

[0087] Example 17. A therapy system comprising: an elongated member configured to navigate within a blood vessel, the elongated member comprising a proximal portion and a distal portion; a plurality of electrodes formed on the distal portion of the elongated member, the electrodes in electrical communication with a source of stimulation; an antenna loop formed on at least one of the electrodes; a sensor loop formed on at least one of the electrodes; and an interrogator in electrical communication with the antenna loop and configured to initiate an interrogator signal comprising a frequency sweep to drive the antenna loop, wherein the interrogator is configured to receive a signal from the sensor loop indicative of a reflected component of the interrogator signal.

[0088] Example 18. The therapy system of Example 17, wherein the antenna loop and the sensor loop are inductively coupled when the antenna loop transmits the interrogator signal.

[0089] Example 19. The therapy system of Example 18, further comprising a therapy source for delivering a therapy to a location of a blood vessel wall.

[0090] Example 20. The treatment system of Example 19, wherein the therapy comprises at least one of: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation.

[0091] Example 21. The treatment system of Example 19, wherein the therapy source is in electrical communication with the electrode for applying the therapy to the location of the vessel wall.

[0092] Example 22. The treatment system of Example 21, further comprising a stimulation source in electrical communication with the electrode, wherein the electrode is configured to apply a stimulation signal to the vessel wall.

[0093] Example 23. The treatment system of Example 22, wherein the stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

[0094] Example 24. The treatment system of Example 23, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor: receives a signal indicative of a reflected component of the interrogator signal; and detects a change in the signal indicative of the reflected component of the interrogator signal.

[0095] Example 25. The treatment system of Example 23, wherein the application, when executed by the processor, and in response to detecting that the change in the signal indicative of the reflected component of the interrogator signal exceeds a threshold, performs an action.

[0096] Example 26. The treatment system of Example 24, wherein the action comprises outputting, to a display device in communication with the computing device, an indication that the change exceeds the threshold or ceasing to apply the therapy to the location of the vessel wall.

[0097] Example 27. The treatment system of Example 17, further comprising: a second antenna loop formed on a second electrode of the at least one electrode; a second sensor loop formed on a second electrode of the at least one electrode; wherein the interrogator is in electrical communication with the second antenna loop and is configured to initiate a second interrogation signal comprising a second frequency sweep to drive the second antenna, wherein the interrogator is configured to receive a second signal from the second sensor loop indicative of a reflected component of the second interrogation signal.

[0098] Example 28. The treatment system of Example 27, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor: receives a signal indicative of a reflected component of the interrogator signal; receives the signal indicative of a reflected component of the second interrogator signal; and calculates a pulse wave velocity or pulse transit time of blood within the blood vessel.

[0099] Example 29. A treatment system comprising: an elongate member configured for navigation within a blood vessel, the elongate member comprising a distal portion and a proximal portion; a plurality of electrodes formed on the distal portion of the elongate member, the electrodes configured to be in electrical communication with a stimulation source; and an ultrasound transducer formed on the elongate member, wherein the ultrasound transducer is configured to detect a signal indicative of a blood vessel murmur of the blood vessel.

[0100] Example 30. The treatment system of Example 29, further comprising a therapy source for delivering a therapy to a location of a blood vessel wall.

[0101] Example 31. The treatment system of Example 30, wherein the therapy comprises at least one of: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation.

[0102] Example 32. The treatment system of Example 30, wherein the therapy source is in electrical communication with the electrodes for applying the therapy to the location of a blood vessel wall.

[0103] Example 33. The treatment system of Example 32, further comprising a stimulation source in electrical communication with the electrodes, wherein the electrodes are configured to apply a stimulation signal to the blood vessel wall.

[0104] Example 34. The treatment system of Example 33, wherein the stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

[0105] Example 35. The treatment system of claim 34, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor: receives the signal indicative of the blood vessel murmur of the blood vessel from the ultrasound transducer; calculates a spectral power from the received signal indicative of a blood vessel murmur; and detects a change in the spectral power.

[0106] Example 36. The treatment system of Example 35, wherein the application, when executed by the processor, and in response to detecting that a change in the spectral power exceeds a threshold, performs an action.

[0107] Example 37. The treatment system of Example 36, wherein the action comprises outputting, to a display device in communication with the computing device, an indication that the change exceeds the threshold or ceasing to apply the therapy to the location of the blood vessel wall.

[0108] Example 38. A method of evaluating a denervation procedure, the method comprising: receiving, by a computing device, a signal indicative of a blood vessel murmur of a blood vessel in which an elongated member has been placed, wherein an ultrasound transducer carried by the elongated member detects the blood vessel murmur; converting, by the computing device, the blood vessel murmur to a spectral power; monitoring the spectral power over time as a therapy is applied to a blood vessel wall of the blood vessel in which the elongated member has been placed; determining that a change in the spectral power over time exceeds a threshold; and in response to determining that the change in the spectral power over time exceeds the threshold, performing an action.

[0109] Example 39. The method of Example 38, wherein performing the action comprises at least one of: outputting an indication that the change exceeds the threshold or ceasing to apply the therapy to the location of the blood vessel.

[0110] Example 40. The method of Example 39, further comprising: applying a stimulation signal from an electrode of a therapeutic device to the blood vessel wall.

[0111] Example 41. The method of Example 40, wherein monitoring the spectral power comprises: observing a response in the spectral power to the stimulation signal.

[0112] Example 42. The method of Example 41, wherein an increase in the spectral power is indicative of a decrease in blood volume within the blood vessel.

[0113] Example 43. The method of Example 42, wherein the stimulation signal causes a decrease in blood volume within the blood vessel by stimulating nerves within or near the blood vessel wall, thereby causing contraction of muscle fibers in the blood vessel.

[0114] Example 44. The method of Example 43, wherein the stimulation signal is part of a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

[0115] Example 45. The method of example 44, wherein monitoring the spectral power comprises: continuously monitoring the spectral power, periodically monitoring the spectral power, or periodically monitoring the spectral power.

[0116] Example 46. The method of example 45, wherein monitoring the spectral power comprises: periodically monitoring the spectral power, wherein the stimulation signal is part of the sequential stimulation protocol or the alternating stimulation protocol, and wherein the periodically monitoring occurs during a stimulation portion of the sequential stimulation protocol or the alternating stimulation protocol.

[0117] Example 47. The method of example 46, wherein the therapy comprises at least one of: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, and cryogenic or chemical denervation.

[0118] Example 48. The method of example 38, wherein a decrease in the spectral power after application of the therapy is indicative of an increase in blood volume within the blood vessel.

[0119] Example 49. The method of example 48, wherein the increase in blood volume within the blood vessel is indicative of successful denervation of nerves in or near the location of the blood vessel wall.

[0120] Example 50. The method of example 38, wherein the blood vessel is one or more of: celiac trunk, hepatic artery, splenic artery, gastric artery, superior mesenteric artery, inferior mesenteric artery, gonadal artery, splanchnic artery, or a branch thereof.

[0121] Further disclosed herein are the subjects of the following clauses:

[0122] 1. A treatment system, comprising:

[0123] an elongated member configured to be navigated within a blood vessel, the elongated member comprising a proximal portion and a distal portion;

[0124] a plurality of electrodes formed on the distal portion of the elongated member, the electrodes in electrical communication with a stimulation source;

[0125] an antenna loop formed on at least one of the electrodes;

[0126] a sensor loop formed on at least one of the electrodes; and

[0127] an interrogator in electrical communication with the antenna loop and configured to initiate an interrogator signal comprising a frequency sweep to drive the antenna loop, wherein the interrogator is configured to receive a signal from the sensor loop indicative of a reflected component of the interrogator signal.

[0128] 2. The treatment system of clause 1, wherein the antenna loop and the sensor loop are inductively coupled when the antenna loop transmits the interrogator signal.

[0129] 3. The treatment system of clause 1 or 2, further comprising a therapy source for delivering a therapy to a location of a blood vessel wall; and / or wherein the therapy comprises at least one of: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation; and / or wherein the therapy source is in electrical communication with the electrode for applying the therapy to the location of the blood vessel wall.

[0130] 4. The treatment system of any one of clauses 1-3, further comprising a stimulation source in electrical communication with the electrode, wherein the electrode is configured to apply a stimulation signal to the blood vessel wall.

[0131] 5. The treatment system of clause 4, wherein the stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

[0132] 6. The treatment system of any one of clauses 1-5, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor:

[0133] receives the signal indicative of the reflected component of the interrogator signal; and

[0134] detects a change in the signal indicative of the reflected component of the interrogator signal.

[0135] 7. The treatment system of clause 6, wherein the application, when executed by the processor, and in response to detecting that the change in the signal indicative of the reflected component of the interrogator signal exceeds a threshold, outputs to a display device in communication with the computing device an indication that the change exceeds the threshold or ceases to apply the therapy to the location of the blood vessel wall.

[0136] 8. The treatment system of any one of clauses 1-7, further comprising:

[0137] a second antenna loop formed on a second electrode of the at least one electrode;

[0138] a second sensor loop formed on a second electrode of the at least one electrode; wherein the interrogator is in electrical communication with the second antenna loop and is configured to initiate a second interrogation signal comprising a second frequency sweep to drive the second antenna, wherein the interrogator is configured to receive a second signal from the second sensor loop indicative of a reflected component of the second interrogation signal.

[0139] 9. The treatment system of clause 8, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor:

[0140] receiving the signal indicative of a reflected component of the interrogator signal;

[0141] receiving the signal indicative of a reflected component of the second interrogator signal; and

[0142] calculating a pulse wave velocity or pulse transit time of blood within the blood vessel.

[0143] 10. A treatment system, comprising:

[0144] an elongated member configured for navigation within a blood vessel, the elongated member comprising a distal portion and a proximal portion;

[0145] a plurality of electrodes formed on the distal portion of the elongated member, the electrodes configured to be in electrical communication with a source of stimulation; and

[0146] an ultrasound transducer formed on the elongated member, wherein the ultrasound transducer is configured to detect a signal indicative of a vascular murmur of the blood vessel.

[0147] 11. The treatment system of clause 10, further comprising a therapy source for delivering a therapy to a location of a blood vessel wall; and / or wherein

[0148] the therapy comprises at least one of: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation, and / or;

[0149] the therapy source is in electrical communication with the electrodes for applying the therapy to the location of the blood vessel wall.

[0150] 12. The treatment system of clause 10 or 11, further comprising a stimulation source in electrical communication with the electrode, wherein the electrode is configured to apply a stimulation signal to the blood vessel wall.

[0151] 13. The treatment system of clause 12, wherein the stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

[0152] 14. The treatment system of any one of clauses 10 to 13, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor:

[0153] receives, from the ultrasound transducer, the signal indicative of the vascular murmur of the blood vessel;

[0154] computes a spectral power from the received signal indicative of a vascular murmur; and

[0155] detects a change in the spectral power.

[0156] 15. The treatment system of clause 14, wherein the application, when executed by the processor, and in response to detecting that the change in the spectral power exceeds a threshold, outputs, to a display device in communication with the computing device, an indication that the change exceeds the threshold or ceases to apply the therapy to the location of the blood vessel wall.

Claims

1. A therapy system comprising: an elongated member configured to be navigated intravascularly, the elongated member including a proximal portion and a distal portion; a plurality of electrodes formed on the distal portion of the elongated member, the electrodes in electrical communication with a stimulation source; an antenna loop formed on at least one of the electrodes; a sensor loop formed on at least one of the electrodes; and an interrogator in electrical communication with the antenna loop and configured to initiate an interrogator signal comprising a frequency sweep to drive the antenna loop, wherein the interrogator is configured to receive a signal from the sensor loop indicative of a reflected component of the interrogator signal.

2. The therapy system of claim 1, wherein the antenna loop and the sensor loop are inductively coupled when the antenna loop transmits the interrogator signal.

3. The therapy system of claim 1 or 2, further comprising a therapy source for delivering a therapy to a location of a vessel wall; and / or wherein the therapy comprises at least one of the following: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation; and / or wherein the therapy source is in electrical communication with the electrodes for applying the therapy to the location of the vessel wall.

4. The therapy system of any one of claims 1 to 3, further comprising a stimulation source in electrical communication with the electrodes, wherein the electrodes are configured to apply a stimulation signal to the vessel wall.

5. The therapy system of claim 4, wherein the stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

6. The therapy system of any one of claims 1 to 5, further comprising a computing device including a processor and a memory having an application stored thereon that, when executed by the processor: receives the signal indicative of the reflected component of the interrogator signal; and detects a change in the signal indicative of the reflected component of the interrogator signal.

7. The therapy system of claim 6, wherein the application, when executed by the processor, and in response to detecting that the change in the signal indicative of the reflected component of the interrogator signal exceeds a threshold, outputs an indication to a display device in communication with the computing device that the change exceeds the threshold or ceases to apply the therapy to the location of the vessel wall.

8. The therapy system of any one of claims 1 to 7, further comprising: a second antenna loop formed on a second electrode of the at least one electrode; ​ a second sensor loop formed on a second electrode of the at least one electrode; wherein the interrogator is in electrical communication with the second antenna loop and is configured to initiate a second interrogation signal comprising a second frequency sweep to drive the second antenna, wherein the interrogator is configured to receive a second signal from the second sensor loop indicative of a reflected component of the second interrogation signal.

9. The treatment system of claim 8, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor: receives the signal indicative of a reflected component of the interrogator signal; receives the signal indicative of a reflected component of the second interrogator signal; and computes a pulse wave velocity or pulse transit time of blood within the blood vessel.

10. A treatment system, comprising: an elongated member configured for navigation within a blood vessel, the elongated member comprising a distal portion and a proximal portion; a plurality of electrodes formed on the distal portion of the elongated member, the electrodes configured to be in electrical communication with a stimulation source; and an ultrasound transducer formed on the elongated member, wherein the ultrasound transducer is configured to detect a signal indicative of a blood vessel murmur of the blood vessel.

11. The treatment system of claim 10, further comprising a therapy source for delivering a therapy to a location of a blood vessel wall; and / or wherein the therapy comprises at least one of the following: monopolar radiofrequency denervation, bipolar radiofrequency denervation, ultrasound denervation, focused ultrasound denervation, cryogenic denervation, or chemical denervation, and / or; the therapy source is in electrical communication with the electrodes for applying the therapy to the location of the blood vessel wall.

12. The treatment system of claim 10 or 11, further comprising a stimulation source in electrical communication with the electrodes, wherein the electrodes are configured to apply a stimulation signal to the blood vessel wall.

13. The treatment system of claim 12, wherein the stimulation source is configured to output a sequential stimulation protocol, an alternating stimulation protocol, or a continuous stimulation protocol.

14. The treatment system of any one of claims 10 to 13, further comprising a computing device comprising a processor and a memory having an application stored thereon that, when executed by the processor: receives the signal indicative of the blood vessel murmur of the blood vessel from the ultrasound transducer; computes a spectral power from the received signal indicative of a blood vessel murmur; and detects a change in the spectral power.

15. The treatment system of claim 14, wherein the application, when executed by the processor, and in response to detecting that the change in the spectral power exceeds a threshold, outputs an indication to a display device in communication with the computing device that the change exceeds the threshold or ceases to apply the therapy to the location of the blood vessel wall.

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