System for denervation of nerves of blood vessels

Abstract

A system and method of performing a treatment procedure, the method comprising: applying a neural denervation therapy to a wall of a blood vessel; monitoring impedance of tissue of the blood vessel; ending the application of the therapy; and displaying, on the user interface, an indication of the efficacy of the neural denervation therapy.

Description

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 363,457, filed April 22, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This disclosure relates to systems and methods for evaluating the efficacy of ablation procedures. In a particular aspect, this disclosure relates to methods and systems for denervating nerves and providing physicians with feedback on the efficacy of denervation therapy. Background Technology

[0003] Catheters have been proposed for use in a variety of medical procedures. For example, catheters can be configured to deliver neuromodulation (e.g., denervation) therapies to target tissue sites to alter the activity of nerves at or near the target tissue site. These nerves can be, for example, the sympathetic or parasympathetic nervous systems. The sympathetic nervous system (SNS) is the primary involuntary bodily control system commonly associated with stress responses. Chronic overactivation of the SNS is an adaptive response that can drive the progression of many disease states. For example, overactivation of the renal SNS has been identified in experiments and in humans as a possible cause of the complex pathophysiology of arrhythmias, hypertension, states of volume overload (e.g., heart failure), and progressive kidney disease.

[0004] Percutaneous renal denervation is a minimally invasive procedure used to treat hypertension and other conditions caused by hyperactivation of the sacral nervous system (SNS). During renal denervation, clinicians deliver stimulation or energy, such as radiofrequency, ultrasound, cooling, or other energy, to the treatment site to reduce perivascular nerve activity. The stimulation or energy delivered to the treatment site can provide various therapeutic effects by altering sympathetic nerve activity.

[0005] During current denervation procedures, clinicians often struggle to assess the progress of the applied therapy and the efficacy of the ablation procedure. Therefore, this disclosure relates to systems and methods that address these shortcomings of current techniques. Summary of the Invention

[0006] One aspect of this disclosure relates to a method of performing a treatment protocol. The method includes applying a nerve denervation therapy to the wall of a blood vessel. The method also includes monitoring the tissue impedance of the blood vessel. The method further includes calculating a linearly scaled impedance value based on the monitored impedance of the blood vessel. The method also includes determining that a value associated with the linearly scaled impedance exceeds a threshold. The method further includes terminating the application of the therapy. The method also includes displaying an indication of the efficacy of the nerve denervation therapy on a user interface. Other embodiments of this aspect include corresponding computer systems, devices, and computer programs, each configured to perform the actions of the methods and systems described herein, stored on one or more computer storage devices.

[0007] Specific implementations of this aspect of the disclosure may include one or more of the following features. The method also includes determining that the therapy has timed out. The threshold is a value of linearly scaled impedance indicating an effective therapy. The method also includes detecting the temperature of the blood vessel. The detected temperature of the blood vessel is the temperature of an electrode. The temperature of the electrode is close to the temperature of the blood vessel wall. The threshold is the difference between the detected temperature and the linearly scaled impedance. The threshold is the integral value of the difference between the linearly scaled impedance and the detected temperature over a period of time. The therapy is monopolar radiofrequency therapy, bipolar radiofrequency therapy, microwave therapy, or ultrasound therapy. The method also includes calculating the impedance of the monitored tissue of the blood vessel based on the current and voltage of the therapy source generating the denervation therapy. The method also includes navigating the treatment device to a location within one or more of the renal artery, celiac artery, hepatic artery, visceral artery, or mesenteric artery. Specific implementations of the described technique may include hardware, methods or processes, or computer software on a computer-accessible medium, including software, firmware, hardware, or combinations thereof installed on a system that causes the system to perform actions during operation. One or more computer programs may be configured to perform specific operations or actions by including instructions that, when executed by a data processing device, cause the device to perform the action.

[0008] A second aspect of this disclosure relates to a system for denervating a nerve in a blood vessel. The system includes a therapeutic device configured for navigation within a patient's blood vessel. The system also includes a plurality of electrodes formed on a distal portion of the therapeutic device and configured to selectively contact the wall of the blood vessel; and a therapeutic source electrically connected to the plurality of electrodes. The system further includes a computing device including a memory and a processor and storing instructions thereon that, when executed,: calculate the impedance of the tissue of the blood vessel; monitor the impedance of the tissue of the blood vessel during the application of therapy to the blood vessel wall; calculate a linearly scaled impedance value based on the monitored impedance of the tissue of the blood vessel; determine that a value associated with the linearly scaled impedance exceeds a threshold; terminate the application of the therapy; and display an indication of the efficacy of the nerve denervation therapy on a user interface. Other embodiments of this aspect include corresponding computer systems, devices, and computer programs, each configured to perform the actions of the methods and systems described herein, stored on one or more computer storage devices.

[0009] Specific implementations of this aspect of the disclosure may include one or more of the following features. The system also includes instructions stored in the memory that, when executed by the processor, determine that the therapy has timed out. The threshold is a value of linearly scaled impedance indicating an effective therapy. The system also includes a sensor in communication with the electrode and configured to determine the temperature of the electrode; the temperature of the electrode is close to the temperature of the blood vessel wall. The threshold is the difference between the detected temperature and the linearly scaled impedance. The threshold is the integral value of the difference between the linearly scaled impedance and the detected temperature over a period of time. The therapy source and the treatment device are configured to apply monopolar radiofrequency therapy, bipolar radiofrequency therapy, microwave therapy, or ultrasound therapy. The treatment device is configured to navigate to a location within one or more of the renal artery, celiac artery, hepatic artery, visceral artery, or mesenteric artery. Specific implementations of the described techniques may include hardware, methods, or processes, or computer software on a computer-accessible medium, including software, firmware, hardware, or combinations thereof installed on a system that causes the system to perform actions during operation. One or more computer programs may be configured to perform specific operations or actions by including instructions that, when executed by a data processing device, cause the device to perform the action.

[0010] This article further discloses a system and method for performing a treatment protocol, the system and method comprising: applying a nerve denervation therapy to the wall of a blood vessel; monitoring the tissue impedance of the blood vessel; terminating the application of the therapy; and displaying an indication of the efficacy of the nerve denervation therapy on a user interface. Attached Figure Description

[0011] Various aspects and embodiments of this disclosure are described below with reference to the accompanying drawings, in which: Figure 1 This is a schematic diagram of the therapeutic system provided in this disclosure; Figure 2 yes Figure 1 A schematic diagram of the workstation of the therapy system; Figure 3 Based on this disclosure Figure 1 A perspective view of the treatment device of the therapy system, which is advanced and deployed within a part of the patient's anatomy. Figure 4 It is by Figure 3 A graph showing the change in impedance measured by the treatment device compared to the change in the measured temperature of the medium in which the treatment device is placed. Figure 5A It is by Figure 1 A graph of in vivo impedance data measured by the treatment device. Figure 5B It is by Figure 1A graph of body temperature data measured by the treatment device; Figure 6A Depicting the overlay after the linear function transformation Figure 5B Temperature data Figure 5A Impedance data; Figure 6B Depicting Figure 6A A graph of the rolling average data; and Figure 7 This is a method for evaluating the efficacy of a treatment based on the present disclosure. Detailed Implementation

[0012] This disclosure relates to treatment systems and methods, and more particularly to ablation systems and methods. In at least one aspect, this disclosure relates to treatment systems and methods for denervation or neuromodulation of nerves, such as sympathetic or parasympathetic nerves. Some aspects of this disclosure relate to the ablation and denervation of unmyelinated nerve fibers within and around blood vessels and other luminal tissues. Specifically, this disclosure relates to systems and methods for providing in-procedure and post-procedure feedback on the efficacy of the therapy.

[0013] For ease of description, most of the following description focuses on the implementation of electrical stimulation and RF denervation. Those skilled in the art will recognize that the methods and systems described herein can employ any of the therapeutic modalities and / or neurostimulation modalities described herein. Similarly, the following description focuses on navigating to and applying neurostimulation and / or therapy to the renal artery to denervate the sympathetic nerves or, in some embodiments, parasympathetic nerves in, around, and near the renal artery. However, this disclosure is not limited thereto. In general, the devices, systems, and techniques described herein can be used in conjunction with neuromodulation (e.g., denervation) performed from any suitable anatomical lumen having 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 arteries and their branches, and the inferior mesenteric artery and its branches, etc. Furthermore, although this disclosure primarily describes neural modulation (e.g., denervation) from one or more arteries, the devices, systems, and techniques of this disclosure can also be applied to neural modulation from one or more veins, such as the renal vein and its branches, the hepatic vein and its branches, or the intercostal vein and its branches. In some specific embodiments, the devices, systems, and techniques described herein can be used to perform neural modulation (e.g., denervation) simultaneously or sequentially from two or more anatomical lumens (e.g., in the renal artery and the common hepatic artery) or any other combination of two or more anatomical lumens. Furthermore, the systems, devices, and methods described herein can be used in conjunction with neural modulation in body cavities other than blood vessels (e.g., denervation), for extravascular neural modulation, and / or for use in conjunction with therapies other than neural modulation.

[0014] Now turn to the attached image. Figure 1 An example of a therapeutic system provided according to this disclosure and generally identified by reference numeral 10 is shown. For example... Figure 1 As shown, the therapy system 10 can be used in conjunction with a C-arm imaging system or other imaging station, which facilitates the navigation of the therapy device 50 to the desired location within the patient's anatomy (e.g., the patient's renal artery), the application of denervation therapy to tissue adjacent to the renal artery to denervate the sympathetic nerves within the tissue, and the monitoring of impedance and temperature for evaluation of the denervation therapy.

[0015] The therapy system 10 includes a workstation 20 and a treatment device 50 operatively coupled to the workstation 20. The therapy system 10 can be used with an imaging device 70 operatively coupled to a display 72. The patient “P” is shown lying on an operating table 12, with the treatment device 50 inserted through a portion of the patient’s femoral artery, although it is contemplated that the treatment device 50 can be inserted into any suitable portion of the patient’s vascular network in fluid communication with the desired vessel for therapy. Although generally described as having one treatment device 50, it is envisioned that the therapy system 10 can employ any suitable number of treatment devices 50. The treatment devices 50 can employ the same or different therapy modalities and are operatively coupled to the workstation 20. Furthermore, without departing from the scope of this disclosure, the treatment device 50 can employ a guidewire or guiding catheter 58. Figure 3 ).

[0016] continue Figure 1 And refer to other sources Figure 2 Workstation 20 includes computer 22 and a therapy source 24 (e.g., one or more of an RF generator, microwave generator, ultrasound generator, cryogenic medium source, chemical source, etc.) operatively coupled to computer 22. In some examples, computer 22 and therapy source 24 are integrated into a single component and may be referred to as a generator.

[0017] 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 Bluetooth, which enables communication with wide area networks (WANs) and / or local area networks (LANs). ®This can be done wirelessly. Network interface 36 can connect to the Internet via one or more gateways, routers, and Network Address Translation (NAT) devices. Network interface 36 can communicate with cloud storage system 38, where additional data, image data, and / or video can be stored. Cloud storage system 38 can be located remotely from the hospital or within a hospital building, such as in a control or hospital IT room. It is envisioned that cloud storage system 38 can also be used 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). Input module 40 receives input from input devices such as keyboards, mice, voice commands, energy source controllers (e.g., foot pedals or handheld remote controls that enable clinicians to start and stop therapy source 24 and / or stimulation source 24a and optionally adjust various operating characteristics (including, but not limited to, power delivery) of the therapy source and / or stimulation source). Output module 42 connects processor 30 and memory 32 to various output devices, such as display 26. In an embodiment, display 26 may be a touch screen display.

[0018] Therapeutic source 24 generates and outputs one or more of the following: RF energy (monopolar or bipolar), microwave energy, ultrasonic energy, cryo-media, or chemical ablation media, via an automatic control algorithm 44 stored in memory 32 and / or under the control of a clinician. As will be understood, many of the therapies listed above alter the temperature of tissue (e.g., raise or lower the temperature) to achieve desired denervation of nerves. Therapeutic source 24 can be configured to generate energy and / or therapy of selected modalities and magnitudes for delivery to the treatment site via treatment device 50, as will be described in further detail below. Therapeutic source 24 can sense voltage and current applied to the target tissue via treatment device 50. Furthermore, one or more sensors on treatment device 50 can monitor the temperature of the target tissue or tissue near the target tissue and / or a portion of treatment device 50. Using the sensed voltage and current applied to the tissue, application 34 on computer 22 calculates the tissue's impedance, through which therapeutic or directed energy is transmitted to provide an indication of the tissue's state. As will be described in further detail below, this status can be output to display 26 on one or more user interfaces 28 to provide clinicians with both in-procedure and post-procedure feedback on the therapy.

[0019] Figure 3An embodiment of a treatment device 50 according to this 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 therapeutic electrodes 56 are located. The elongated shaft 52 of the treatment device 50 is configured to advance within a guidewire (not shown) on a portion of the patient's vascular system, such as the femoral artery or another suitable portion of the patient's vascular network in fluid communication with the patient's renal artery. In an embodiment, the energy delivery assembly 54 is configured to transition from an initial undeployed configuration having a generally linear profile to a second deployed or expanded configuration, wherein the energy delivery assembly 54 forms a generally helical and / or spiral configuration for delivering energy to a treatment site to apply one or both of a stimulation signal or therapeutic energy at the treatment site. Those skilled in the art will recognize that, in the context of this application, the application of therapeutic energy should be interpreted as including applying cryogenic cooling to the treatment site to achieve thermally induced neuromodulation. In this way, when in the second expanded configuration, the energy delivery assembly 54, and in particular the individual electrode 56, presses against or otherwise contacts the wall of the patient's vascular system tissue. Although generally described as transitioning to a helical and / or spiral configuration, it is contemplated that the energy delivery assembly 54 can be deployed in other configurations without departing from the scope of this disclosure. Additionally, the treatment device 50 can be configurable, for example, using one or more drawstrings (not shown) to adjust the configuration to facilitate contact between the electrode 56 and the wall of the renal artery. Thus, the treatment device 50 can be positioned in one, two, three, four, or more different configurations depending on the design requirements of the treatment device 50 or the location where the therapy is to be applied.

[0020] like Figure 3 As depicted, the elongated shaft 52 can be configured to be received within a portion of a guiding catheter or guiding sheath (such as a 6F guiding catheter) 58, which is used to navigate the treatment device 50 to a desired location. In practice, the guiding catheter 58 is inserted into an access point such as the femoral artery to obtain access to the vascular system. The guiding catheter 58 is advanced to the desired location, for example, to cannulate the renal artery. A guidewire (not shown) is advanced through the guiding catheter 58 and to the location where therapy is to be applied (i.e., beyond the distal end of the guiding catheter 58) and into the desired vessel (e.g., the renal artery). The treatment device 50 is then advanced over the guidewire to the location where therapy is to be applied, thereby exposing the electrode 56. The guidewire 50 is then retracted into the treatment device 50 and the guiding catheter 58. The retraction of the guidewire within the treatment device 50 causes the energy of the delivery component 54 of the treatment device 50 to change from a first undeployed and generally straight configuration to a second deployed or expanded configuration (e.g., ...). Figure 3(As shown). In some specific embodiments, sensor 60 may be incorporated into guide sheath 58 or shaft 62 for detecting a patient's physiological parameters. In one example, the physiological parameter is blood pressure, but other parameters may be used without departing from the scope of this disclosure. Although described herein as advancing treatment device 50 beyond guide catheter 58, in some configurations, guide catheter 58 may be retracted relative to treatment device 50 to achieve desired placement of electrode 56. Furthermore, although described herein in conjunction with guidewire, guidewire is not required, and the placement described above can be achieved without the use of guidewire (e.g., using only guide catheter).

[0021] The elongated shaft 52 of the treatment device 50 may further include an aperture (not shown) at its distal end, configured to slidably receive a guidewire over which the treatment device 50 is advanced, alone or in combination with a guiding catheter 58. In this way, the treatment device 50 is guided to the target tissue using an over-the-wire (OTW) or rapid exchange (RX) technique, at which point the guidewire can be partially or completely removed from the treatment device 50, allowing the treatment device 50 to transition from a first undeployed configuration to a second deployed or expanded configuration. Figure 3 As noted elsewhere in this document, the treatment device 50 can be automatically (e.g., via shape memory alloy, etc.) or manually (e.g., via a draw wire, guidewire manipulation, etc. controlled by a clinician) converted from a first undeployed configuration to a second deployed configuration.

[0022] Continue to refer to Figure 3 In an embodiment where the treatment device 50 is an RF ablation catheter, the energy delivery assembly 54 includes one or more electrodes 56 disposed on its outer surface, the one or more electrodes being configured to contact a portion of a patient's vascular tissue when the treatment device 50 is positioned in a second dilation configuration. As shown herein, the treatment device 50 includes four electrodes 56. However, this disclosure is not limited thereto, and the treatment device 50 may have more or fewer electrodes 56 without departing from the scope of this disclosure. Those skilled in the art will recognize that the electrodes 56 may be replaced using an ultrasound transducer, a microwave antenna, a port for delivering cryoablation media or chemical media, and other instruments and / or ablation and denervation modalities without departing from the scope of this disclosure.

[0023] As illustrated, electrodes 56 are arranged spaced apart from each other along the length of the treatment device 50, thereby forming an energy delivery assembly 54. As will be understood, 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 the sympathetic nerves of the relevant blood vessel. The electrodes 56 can deliver RF energy independently, simultaneously, selectively, or sequentially, and are electrically connected to a grounding pad (not shown) to enable the application of monopolar RF energy for therapy. Additionally or alternatively, RF energy can be applied between any desired combination of electrodes 56 without the need for a grounding pad (e.g., bipolar).

[0024] Therapies (e.g., RF, microwave, or ultrasound energy) typically raise the temperature of the tissue receiving the therapeutic energy. Similarly, when a therapy is applied to electrode 56, and there the tissue receives energy (e.g., a blood vessel wall) to attempt denervation of afferent nerves located within and outside the blood vessel wall, the impedance of the tissue through which the energy passes can be calculated by the therapy source 24 or a computer 22 operatively connected thereto. Following Ohm's law, the impedance of the tissue can be calculated given that the voltage and current output of the therapy source 24 are known. As those skilled in the art will understand, the impedance of the tissue decreases when therapeutic energy is applied to the tissue and the tissue is heated.

[0025] Figure 4 Two graphs were plotted during the experimental application of energy to a treatment device 50 placed in a saline bath. The first graph depicts the linearly scaled impedance observed during the application of therapeutic energy, while the second graph depicts the temperature change observed due to the applied energy. The linear scaling of the impedance value was achieved using the linear formula (1) and the temperature and impedance values ​​at two times (t1) and (t2): (1) T=m I+c in: T = Temperature I = impedance m = the ratio of temperature change to impedance change between time t1 and t2 c = constant Then, use formula (2) to calculate the impedance value of the linear scaling: (2) LSI=m I+c As noted above, two time points (t1) and (t2) are selected. These can be specific times during the application of the therapy (e.g., at 5s and 20s), or they can be time ranges (e.g., 5s to 10s and 15s to 20s). At each time point (t1) and (t2), temperature and impedance values ​​are determined to provide T1, I1 values ​​and T2, I2 values. When using a time range, the average temperature and impedance values ​​across that time range can be calculated. Using Equation (1), the values ​​of m and c are determined by solving Equation (1) for each time (t1) and (t2), therefore: At (t1), T1=m I1+c At (t2), T2=m I2+c Subtract Formula 1 at (t2) from Formula 1 at (t1): T2–T1 = m(I2–I1) With all other values ​​known, m can be solved as: m=(T2–T1) / (I2-I1) Furthermore, c can be solved from Equation 1 at (t1) or (t2), for example: c=T2–m I2

[0026] Once m and c are resolved, the linearly scaled impedance (LSI) can be calculated using formula (2) whenever impedance data is available. Figure 4 As can be seen, temperature and linearly scaled impedance are almost perfectly correlated (i.e., an increase in linearly scaled impedance is highly correlated with an increase in temperature). In the experimental context, the conductivity of the brine increases with increasing temperature. Therefore, an increase in temperature is associated with a decrease in resistance, or impedance. Figure 4 During the process, therapeutic energy (e.g., ablation or denervation energy) is initially applied at the 10-second mark and stops at the 70-second mark.

[0027] As will be understood, Figure 4 The experimental results described show a relationship between temperature and impedance. However, this is proof of a virtually "perfect" experiment. It is a perfect experiment in the sense that each of the electrodes 56 in the treatment device 50 is completely immersed in the saline solution. Because the electrodes 56 are completely submerged, 100% of the electrode surface area is exposed to and in contact with the saline solution. Therefore, throughout the experiment, the impedance of the saline solution is only a function of its temperature. This is achieved in part by minimizing any changes in the salinity of the saline solution by restricting evaporation. Figure 4 As shown in the graph, this experiment demonstrates the primary relationship between impedance and temperature.

[0028] Those skilled in the art will recognize that when treating a patient, blood vessels (e.g., renal arteries) do not present a homogeneous medium for applying energy and measuring the effect of that application. When therapy is applied to a blood vessel, impedance is no longer purely a function of temperature. In addition to temperature, impedance is a function of the degree of contact between electrode 56 and the vessel wall. Blood in a blood vessel is generally more conductive than the tissue of the vessel wall, so impedance will change as the surface area of ​​electrode 56 changes in contact with the vessel wall. Several factors can affect the surface area of ​​electrode 56 in contact with the vessel wall, one such factor being the patient's heartbeat, which causes the diameter of the vessel to change as the volume of blood forced through the vessel increases and decreases during the cardiac cycle. Another reason for the change in impedance experienced in vivo when therapy is applied is permanent and irreversible tissue damage caused by the applied therapeutic energy. To a large extent, this permanent tissue damage is the dehydration of the vessel wall cells and other tissues of the blood vessel, including nerves that are targets of denervation. This dehydration of tissues permanently alters tissue impedance even when the temperature of the tissue returns to baseline. These more complex relationships must be considered in order to provide an accurate and useful feedback mechanism for clinicians to use during procedures.

[0029] According to one aspect of this disclosure, each electrode may be combined with a thermistor or other temperature sensor (not shown) to enable monitoring of the temperature of electrode 56. As will be understood, electrode 56 is in direct contact with the inner wall of a blood vessel or other luminal tissue, so that when energy passes through electrode 56, it heats adjacent electrodes, causing electrode 56 itself to begin heating. A thermistor, thermocouple, or other temperature sensor in communication with electrode 56 generates a signal received by therapeutic source 24 and provides an indication of the temperature of electrode 56. The temperature of electrode 56 is very close to the temperature of the tissue of the blood vessel directly adjacent to electrode 56.

[0030] According to this disclosure, the temperature of electrode 56, as measured by a temperature sensor (which is an approximation of the temperature of the tissue receiving the therapy), can be compared with linearly scaled impedance data to assess the efficacy of the therapy. Figure 5A Impedance data were obtained from the application of therapeutic energy within the body to the patient's blood vessel walls. (Compared to...) Figure 4 Similarly, therapeutic energy is applied via electrode 56, starting at the 10-second mark on the graph and ending at approximately the 70-second mark. The oscillations depicted in the graph data are correlated with the patient's heartbeat and reflect changes in the degree of contact between electrode 56 and the blood vessel wall. Figure 5B A graph depicting the temperature of the electrode during the same time period when therapeutic energy is applied to the patient's blood vessels is plotted. (Compared to...) Figure 5ASimilar to the impedance data plotted in the figure, oscillations are also observed in the plotted temperature data. However, unlike the impedance data plotted in the figure, the oscillations only begin after the application of therapeutic energy (e.g., ablation) has started. Once the therapeutic energy is applied (marked at 10 seconds in the figure), a temperature gradient is established between the vessel wall and the blood flowing through it. During the application of therapeutic energy, the vessel wall is warmer than the blood flowing through it. Furthermore, the pulsating flow of body-temperature blood through the vessel (e.g., renal artery) and the varying degrees of contact between the electrode 56 and the tissue of the vessel wall cause the thermal convection capacity of the blood to change over time, resulting in the oscillations observed in the figure. Although in Figure 5A and Figure 5B Oscillations are observed in the curve, but a correlation or relationship between the impedance data and the temperature data can be observed.

[0031] Figure 6A Depicting in Figure 5B Plotted on temperature data after applying a linear function transformation. Figure 5A Impedance data. Figure 6B The curve depicts the effect of applying therapeutic energy to the vessel wall via electrode 56 when converted to a rolling average. Figure 6A The same data. Figure 6B In this process, the oscillation is smoothed by averaging the data and reducing the impact of changes in the contact between electrode 56 and the blood vessel wall caused by changes in the patient's heart rate and blood vessel diameter.

[0032] like Figure 6B As can be seen, from the application of healing energy at approximately the 10-second mark on the graph to approximately the 25-second mark, the temperature data and the linearly scaled impedance data are strongly correlated, as shown in the graph overlay. For Figure 6B In the remainder of the graph, the linearly scaled impedance and temperature data separate, partly due to the onset of permanent tissue damage as described above. This separation results in a tracking error between the temperature and impedance data from approximately 25 seconds until the application of therapeutic energy to the vessel wall ceases. As the application of therapeutic energy continues, the tracking error between the temperature and impedance data increases. This increase in tracking error is a component of the decrease in impedance (see [link to relevant documentation]). Figure 5A (Impedance without linear scaling), this component is associated with the increase in permanent tissue changes (e.g., damage) as the application of therapeutic energy continues. The greater the tracking error, the greater the degree of tissue damage achieved by applying therapeutic energy.

[0033] like Figure 6B As shown, linearly scaled impedance data, and in particular tracking error, can be used to provide clinicians with information about the effectiveness of applying therapeutic energy to the vessel wall. Additionally or alternatively, Figure 6BThe tracking error described herein can be used to provide the endpoint of treatment. When the tracking error reaches a set value, the treatment can be stopped because the magnitude of the tracking error (e.g., impedance value) indicates a certain temperature that has been reached in tissue beyond the blood vessel wall. This provides an indication of the efficacy of the treatment.

[0034] Although a general description has been given above in conjunction with denervation, this disclosure is not limited thereto. The use of linearly scaled impedance to estimate temperature or as a representative of temperature can be achieved in other ways, including but not limited to stimulation or other neuromodulation of nerves within or around blood vessels or other luminal tissues.

[0035] Figure 7 A flowchart of method 700 according to this disclosure is depicted. At step 702, the treatment device 50 is placed at a desired location within the patient's body (e.g., in a kidney or hepatic artery). As part of the placement, the treatment device 50 may be advanced from a catheter 58, and the treatment device 50 is allowed to expand such that the electrode 56 contacts the inner wall of the blood vessel.

[0036] At step 704, a treatment (e.g., RF, microwave, ultrasound ablation, etc.) is applied to the vessel wall to denervate nerves within and outside the vessel wall. At step 706, while the treatment is being applied, the impedance of the tissue through which the treatment passes is monitored. While the impedance is being monitored, a linearly scaled impedance is calculated at step 708. At step 710, it is determined whether the linearly scaled impedance has exceeded a threshold (e.g., a threshold indicating that an effective treatment has been applied). Additionally or alternatively, the threshold may be a threshold difference between the linearly scaled impedance and the temperature detected at electrode 56, as described above. If yes, the method proceeds to step 712, where the treatment application ends, and then proceeds to step 714, where an efficacy indicator is displayed on user interface 28 on display 26. If no at step 710, the method moves to step 716, where it is determined whether the treatment has timed out (e.g., the treatment has been applied for more than 60 seconds). If so, the method proceeds to step 712, the treatment application ends, and an efficacy indicator is displayed at step 714. However, if the treatment has not yet timed out, the method returns to step 704 and the treatment application continues.

[0037] Regarding step 710, the linearly scaled impedance calculated at step 708 can be compared with a temperature value indicating effective therapy. Therefore, even if the programmed duration for therapy application (e.g., 60 seconds) has not yet been reached, but the necessary temperature indicating effective denervation has been reached, the method can be stopped, and unnecessary therapy application can be minimized. Additionally or alternatively, the determination that the linearly scaled impedance exceeds a threshold can be a more complex determination, employing the integral over time of the difference between the linearly scaled impedance calculated as described above and the temperature of electrode 56 (an approximation of the vessel wall temperature). When the difference exceeds the threshold, the method proceeds to step 712 and terminates the therapy application.

[0038] At step 714, if the efficacy indicator is sufficient to convince the clinician that the complete treatment has been achieved, the method may return to step 702 to locate another position in the same or a different blood vessel, and method 700 may be repeated. Alternatively, if the efficacy indicator signals to the clinician that the treatment is ineffective or insufficiently effective, method 700 may return to step 710, in which the treatment is applied again. This may be repeated until an effective treatment has been achieved at step 714, or until further applications of treatment do not alter the efficacy indicator, at which point the clinician may stop method 700.

[0039] As described herein, at step 714 of method 700, an indicator of therapeutic efficacy is displayed on UI 28. This indicator can be as simple as a color-coded display, where a red indicator signals ineffective or incomplete therapy, and a green indicator signals effective therapy. Alternatively or additionally, the indicator can be more granular and can display the percentage of therapy completion based on the monitored impedance. This can be coupled with more colors, where red represents 0% to 50% completion, orange 50% to 75% completion, yellow 75% to 95% completion, and green greater than 95% completion. Alternatively, UI 21 can display a scrolling indicator of impedance values ​​during therapy application at step 704 and the linearly scaled impedance calculation at step 708. In this way, clinicians can observe changes in impedance during the procedure and assess whether to terminate method 700 spontaneously during the procedure. Without departing from the scope of this disclosure, other indicators may include written words on UI 28, audible sounds indicating the efficacy of a therapy, and combinations of each of these.

[0040] The therapeutic device 50 contemplated in this disclosure can apply one or more of a variety of therapeutic modalities. For example, therapeutic modalities considered within the scope of this disclosure include monopolar or bipolar radiofrequency, microwave, ultrasound, and other modalities yet to be developed. Any of these therapeutic modalities can be incorporated into the therapeutic device 50, which is configured to navigate to a desired location within the patient's body. The therapeutic device 50, configured to deliver one or more of these therapeutic modalities, can be percutaneously navigated, for example via the femoral artery, to reach vessels of the aorta, including the celiac artery, hepatic artery, visceral artery, mesenteric artery, and other arteries weakened by or near one or more sympathetic ganglia. Such catheters can also be placed laparoscopically into one or more of the above-identified vessels or into another luminal tissue without departing from the scope of this disclosure.

[0041] According to various aspects of this disclosure, the treatment device can be navigated within a blood vessel or lumen tissue in one configuration (e.g., a linear configuration) and, once positioned at a desired location, can be deployed or otherwise actuated to achieve a second configuration.

[0042] To date, treatment device 50 has primarily been associated with shape memory construction, wherein a shape memory alloy is released from the outlet of a guiding catheter 58 to achieve a desired helical shape, and an electrode 56 is placed on the vessel wall. However, this disclosure is not limited thereto, and treatment device 50 may be configured such that the electrode is placed on a balloon or other mechanism to achieve desired contact with the vessel wall without departing from the scope of this disclosure.

[0043] Although generally described above, it is contemplated that memory 32 may include any non-transitory computer-readable storage medium for storing data and / or software, including instructions executable by processor 30 and controlling the operation of workstation 20, and in some embodiments, also controlling the operation of treatment device 50. In embodiments, memory 32 may include one or more storage devices, such as solid-state storage devices, for example, flash memory chips. Alternatively, or in addition to such one or more solid-state storage devices, memory 32 may include one or more mass storage devices connected to processor 30 via a mass storage controller (not shown) and a communication bus (not shown).

[0044] The description of computer-readable media as used herein refers to solid-state storage. Those skilled in the art will understand that computer-readable storage media can be any medium accessible by processor 30. That is, computer-readable storage media can include non-transitory, volatile and non-volatile, removable and non-removable media implemented using any information storage method or technology, 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 technologies, CD-ROM, DVD, Blu-ray or other optical storage devices, magnetic tape cassettes, magnetic tape, disk storage devices or other magnetic storage devices, or any other medium that can be used to store desired information and is accessible to workstation 20.

[0045] Example

[0046] The various aspects of this disclosure are further described in conjunction with the embodiments numbered below.

[0047] Example 1: A method for performing a treatment protocol, the method comprising: applying a nerve denervation therapy to the wall of a blood vessel; monitoring the tissue impedance of the blood vessel; calculating a linearly scaled impedance value based on the monitored impedance of the blood vessel; determining that a value associated with the linearly scaled impedance exceeds a threshold; terminating the application of the therapy; and displaying an indication of the efficacy of the nerve denervation therapy on a user interface.

[0048] Example 2: According to the method described in Example 1, the method further includes: determining that the therapy has timed out.

[0049] Example 3: The method according to Example 1 or 2, wherein the threshold is a value of impedance indicating linear scaling of an effective therapy.

[0050] Example 4: The method according to Example 1 or 2 further includes: detecting the temperature of the blood vessel.

[0051] Example 5: The method described in Example 4, wherein the detected temperature of the blood vessel is the temperature of the electrode.

[0052] Example 6: According to the method described in Example 5, the temperature of the electrode is close to the temperature of the blood vessel wall.

[0053] Example 7: The method according to any one of Examples 4 to 6, the method further includes: comparing the linearly scaled impedance value with the detected temperature of the blood vessel, wherein the threshold is the difference between the detected temperature and the linearly scaled impedance.

[0054] Example 8: The method according to any one of Examples 4 to 7, wherein the threshold is the integral value of the difference between the linearly scaled impedance and the detected temperature over a period of time.

[0055] Example 9: The method according to any one of the foregoing examples, wherein the therapy is monopolar radiofrequency therapy, bipolar radiofrequency therapy, microwave therapy, or ultrasound therapy.

[0056] Example 10: The method according to any one of the preceding embodiments further includes: calculating the impedance of the monitored blood vessel tissue based on the current and voltage of the therapeutic source that generates the nerve denervation therapy.

[0057] Example 11: The method according to any one of the foregoing embodiments further includes: navigating the treatment device to a location among one or more of the renal artery, celiac artery, hepatic artery, visceral artery or mesenteric artery.

[0058] Example 12: A system for denervation of a blood vessel, the system comprising: a treatment device configured for navigation within a patient's blood vessel; a plurality of electrodes formed on a distal portion of the treatment device and configured to selectively contact the wall of the blood vessel; a therapy source electrically connected to the plurality of electrodes; and a computing device including a memory and a processor and storing instructions thereon, the instructions, when executed,: calculating the impedance of the tissue of the blood vessel; monitoring the impedance of the tissue of the blood vessel during the application of therapy to the blood vessel wall; calculating a linearly scaled impedance value based on the monitored impedance of the tissue of the blood vessel; determining that a value associated with the linearly scaled impedance exceeds a threshold; terminating the application of the therapy; and displaying an indication of the efficacy of the denervation therapy on a user interface.

[0059] Example 13: The system according to Example 12 further includes instructions stored in the memory, which determine, when executed by the processor, that the therapy has timed out.

[0060] Example 14: The system according to Example 12 or 13, wherein the threshold is a value of impedance that indicates a linear scaling of an effective therapy.

[0061] Example 15: The system according to Example 12 further includes a sensor that is in communication with the electrode and configured to determine the temperature of the electrode.

[0062] Example 16: The system according to Example 15, wherein the temperature of the electrode is close to the temperature of the blood vessel wall.

[0063] Example 17: According to the system of Example 15 or 16, the system further includes instructions stored in the memory, which, when executed by the processor, compare the linearly scaled impedance value with the detected temperature of the blood vessel, wherein the threshold is the difference between the detected temperature and the linearly scaled impedance.

[0064] Example 18: The system according to any one of Examples 15 to 17, wherein the threshold is the integral value of the difference between the linearly scaled impedance and the detected temperature over a period of time.

[0065] Example 19: The system according to any one of Examples 12 to 18, wherein the therapeutic source and the therapeutic device are configured to apply monopolar radiofrequency therapy, bipolar radiofrequency therapy, microwave therapy, or ultrasound therapy.

[0066] Example 20: The system according to any one of Examples 12 to 19, wherein the treatment device is configured to navigate to a location within one or more of the renal artery, celiac artery, hepatic artery, visceral artery or mesenteric artery.

[0067] While several embodiments of this disclosure have been shown in the accompanying drawings, it is not intended to limit this disclosure, as it is desired that this disclosure be as broad as permitted by the art to which it pertains and that this specification should be read in the same manner. Therefore, the above description should not be construed as restrictive, but merely as illustrative of embodiments. Those skilled in the art will be able to conceive of other modifications within the scope and spirit of the appended claims.

Claims

1. A method for performing a treatment protocol, the method comprising: Apply nerve denervation therapy to the wall of the blood vessel; Monitor the impedance of the tissue in the blood vessel; The linearly scaled impedance value is calculated based on the impedance of the monitored blood vessel. The value associated with the linearly scaled impedance is determined to exceed a threshold; End the application of the therapy; as well as The user interface displays an indication of the efficacy of the described denervation therapy.

2. The method according to claim 1, further comprising: It has been determined that the treatment has expired.

3. The method of claim 1 or 2, wherein the threshold is a value of impedance indicating linear scaling of an effective therapy.

4. The method according to claim 1 or 2, further comprising: The temperature of the blood vessel is detected.

5. The method of claim 4, wherein the detected temperature of the blood vessel is the temperature of the electrode.

6. The method of claim 5, wherein the temperature of the electrode is close to the temperature of the blood vessel wall.

7. The method according to any one of claims 4 to 6, further comprising: The linearly scaled impedance value is compared with the detected temperature of the blood vessel, wherein the threshold is the difference between the detected temperature and the linearly scaled impedance.

8. The method according to any one of claims 4 to 7, wherein the threshold is the integral value of the difference between the linearly scaled impedance and the detected temperature over a period of time.

9. The method according to any one of the preceding claims, wherein the therapy is monopolar radiofrequency therapy, bipolar radiofrequency therapy, microwave therapy, or ultrasound therapy.

10. The method according to any one of the preceding claims, further comprising: The impedance of the monitored blood vessel is calculated based on the current and voltage of the therapeutic source that generates the nerve denervation therapy.

11. The method according to any one of the preceding claims, further comprising: The treatment device is guided to a location within one or more of the renal artery, celiac artery, hepatic artery, visceral artery, or mesenteric artery.

12. A system for denervation of nerves in blood vessels, the system comprising: A treatment device configured for navigation within a patient's blood vessels; Multiple electrodes are formed on the distal portion of the treatment device and configured to selectively contact the wall of the blood vessel; A therapeutic source, wherein the therapeutic source is electrically connected to the plurality of electrodes; and A computing device, comprising a memory and a processor and storing instructions thereon, wherein when the instructions are executed: Calculate the impedance of the tissue containing the blood vessel; Monitor the impedance of the tissue of the blood vessel during the application of therapy to the vessel wall; A linearly scaled impedance value is calculated based on the impedance of the tissue in the monitored blood vessel; The value associated with the linearly scaled impedance is determined to exceed a threshold; End the application of the therapy; as well as The user interface displays indicators of the efficacy of the nerve denervation therapy.

13. The system of claim 12, further comprising instructions stored in the memory, the instructions determining, when executed by the processor, that the therapy has timed out.

14. The system of claim 12 or 13, wherein the threshold is a value of impedance that indicates a linear scaling of an effective therapy.

15. The system of claim 12, further comprising a sensor in communication with the electrode and configured to determine the temperature of the electrode.

16. The system of claim 15, wherein the temperature of the electrode is close to the temperature of the blood vessel wall.

17. The system of claim 15 or 16, further comprising instructions stored in the memory, the instructions, when executed by the processor, comparing the linearly scaled impedance value with the detected temperature of the blood vessel, wherein the threshold is the difference between the detected temperature and the linearly scaled impedance.

18. The system according to any one of claims 15 to 17, wherein the threshold is the integral value of the difference between the linearly scaled impedance and the detected temperature over a period of time.

19. The system according to any one of claims 12 to 18, wherein the therapeutic source and the therapeutic device are configured to apply monopolar radiofrequency therapy, bipolar radiofrequency therapy, microwave therapy, or ultrasound therapy.

20. The system according to any one of claims 12 to 19, wherein the treatment device is configured to navigate to a location within one or more of the renal artery, celiac artery, hepatic artery, visceral artery, or mesenteric artery.

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