Environment quantification of renal denervation therapy

Abstract

A system and method for denervation of nerves of a blood vessel including a catheter for navigation a blood vessel of a patient, the catheter comprising a therapeutic element configured to apply a therapy to nerves adjacent the blood vessel, a therapy source in communication with the therapeutic element and configured to generate therapeutic energy and output the therapeutic energy to the therapeutic element, and a computing device including a processor and memory, the memory storing therein instructions that, when executed by the processor, cause the processor to cause the therapy source to generate therapeutic energy and output the therapeutic energy to the therapeutic element, detect a rate of change of temperature associated with the therapeutic element, and determine an environment of the therapeutic element based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element.

Description

ENVIRONMENT QUANTIFICATION OF RENAL DENERVATION THERAPY

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 653,432, filed May 30, 2024, the entire content of which is incorporated herein by reference.Technical Field

[0002] This disclosure relates to systems and methods assessing placement of an ablation probe within a blood vessel. Further, aspects of the disclosure are directed to methods and systems for quantification of an environment for renal neuromodulation.Background

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

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

[0005] One aspect of the disclosure is a system for denervation of nerves of a blood vessel. The system includes a catheter configured to be navigated within a blood vessel of a patient, the catheter may include at least one therapeutic element configured to apply a therapy to nerves adjacent the blood vessel; a therapy source in communication with the at least one therapeuticelement and configured to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; and a computing device including a processor and memory, the memory storing therein instructions that, when executed by the processor, cause the processor to: cause the therapy source to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; detect a rate of change of temperature associated with the at least one therapeutic element; and determine an environment of the at least one therapeutic element based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element. 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.

[0006] Implementations may include one or more of the following features. The system where the instructions when executed by the processor, cause the processor to: determine an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element; and output, for display at a user interface of the computing device, an indicator of efficacy of the therapy. The therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy. The therapeutic element may include a plurality of electrodes or at least one ultrasound transducer. The instructions, when executed by the processor, cause the processor to determine a corresponding environment for each of the plurality of electrodes or at least one ultrasound transducer. The instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with less than all of the electrodes or at least one ultrasound transducers exceed a threshold value; and output for display on a user interface of the computing device an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer. The instructions, when executed by the processor, cause the processor to output for display on the user interface of the computing device an indicator of which electrode of the plurality of electrodes or the at least one ultrasound transducer experienced a rate of change of temperature in excess of the threshold value. The instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with the at least one therapeutic element exceeds a threshold value; and in response to the determination that the rate of change of temperature exceeds the threshold value, cause the therapy source to reduce a power of the therapeutic energy. The memory further stores therein instructions that, when executed by the processor, cause the processor to receivevia a user interface a confirmation that the at least one therapeutic element is located within a blood vessel branch. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium.

[0007] Another aspect of the disclosure is a system for denervation of nerves of a blood vessel. The system includes a catheter configured to be navigated within a blood vessel of a patient, the catheter may include at least one therapeutic element configured to apply a therapy to nerves adjacent the blood vessel; a therapy source in communication with the at least one therapeutic element and configured to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; and a computing device including a processor and memory, the memory storing therein instructions that, when executed by the processor, cause the processor to: receive a selection of therapeutic element placement; set a power of the therapeutic energy of the therapy source based on the selection of therapeutic element placement; cause the therapy source to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; and detect a rate of change of temperature associated with the at least one therapeutic element. 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.

[0008] Implementations may include one or more of the following features. The system where the instructions when executed by the processor, cause the processor to: determine an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with at least one therapeutic element; and output, for display at a user interface of the computing device an indicator of efficacy of the therapy. The therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy. The therapeutic element may include a plurality of electrodes or at least one ultrasound transducer. The instructions when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with one or more of the electrodes or at least one ultrasound transducer exceeds a threshold value, and output for display on a user interface of the computing device an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer. The instructions when executed by the processor cause the processor to output for display on the user interface of the computing device an indicator of which electrode of the plurality of electrodes or the at least one ultrasound transducer experienced a rate of change of temperature in excess of the threshold value. Implementations of the describedtechniques may include hardware, a method or process, or computer software on a computer- accessible medium.

[0009] One general aspect includes a method of identifying an environment of a therapeutic device. The method also includes generating a therapeutic energy at a therapy source; delivering the therapeutic energy to a therapeutic element for application to a blood vessel wall, determining a rate of change of temperature associated with the therapeutic element, and determining an environment of the therapeutic element based at least in part on a detected rate of change of temperature associated with the therapeutic element. 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.

[0010] Implementations may include one or more of the following features. The method may include determining an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with the therapeutic element: and displaying at a user interface of a computing device an indicator of efficacy of the therapy. The therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy. The therapeutic element may include a plurality of electrodes or at least one ultrasound transducer and may include: determining that the rate of change of temperature associated with all of the electrodes or ultrasound transducers exceeds a threshold value; and reducing a power of the therapeutic energy output by the therapy source. The therapeutic element is a plurality of electrodes or ultrasound transducers and may include: determining that the rate of change of temperature associated with less than all of the electrodes or at least one ultrasound transducer exceed a threshold value; and displaying on a user interface an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium.

[0011] Further disclosed herein is a system and method for denervation of nerves of a blood vessel including a catheter for navigation a blood vessel of a patient, the catheter comprising a therapeutic element configured to apply a therapy to nerves adjacent the blood vessel, a therapy source in communication with the therapeutic element and configured to generate therapeutic energy and output the therapeutic energy to the therapeutic element, and a computing device including a processor and memory, the memory storing thereininstructions that, when executed by the processor, cause the processor to cause the therapy source to generate therapeutic energy and output the therapeutic energy to the therapeutic element, detect a rate of change of temperature associated with the therapeutic element, and determine an environment of the therapeutic element based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element.BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Various aspects and embodiments of the disclosure are described hereinbelow with references to the drawings, wherein:

[0013] FIG. l is a schematic diagram of a therapy system provided in accordance with some examples of the disclosure;

[0014] FIG. 2 is a schematic view of a workstation of the therapy system of FIG. 1;

[0015] FIG. 3 is a perspective view of a therapeutic device of the therapy system of FIG.1 advanced within a portion of the patient’s anatomy and in a deployed condition in accordance with some examples of the disclosure;

[0016] FIG. 4 depicts a series of plots of data related to the application of therapy to tissue for denervation in accordance with some examples of the disclosure;

[0017] FIG. 5 is a flow chart outlining a method in accordance with some examples of the disclosure;

[0018] FIG. 6 is a flow chart outlining a method in accordance with some examples of the disclosure; and

[0019] FIG. 7 is a plot of therapy application in accordance with some examples of the disclosure.DETAILED DESCRIPTION

[0020] This disclosure is directed to therapeutic systems and methods and particularly ablation systems and methods for denervation or neuromodulation of nerves such as sympathetic, or parasympathetic, nerves. Some aspects of the disclosure are directed to ablation and denervation of unmyelinated nerve fibers in and around blood vessels and other luminal tissues. In particular, this disclosure is directed to systems and methods that provide preprocedural assessment of placement of a therapeutic device within a blood vessel and quantification of the environment within which the therapeutic device is placed. In accordance with one aspect of the disclosure, during an initial period of application of therapeutic energy to nerves proximate a blood vessel or other luminal tissue, a power level and rate of change of temperature of electrodes is observed. Depending on the power level and the rate of change intemperature observed during the initial application of energy, determinations can be made regarding the placement of the therapeutic device. Further, a determination can be made regarding the environment (e.g., whether the therapeutic device is in a main artery or a branch of the artery) and the power and duration of the therapy can be adjusted in accordance with the determined environment.

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

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

[0023] The therapy system 10 includes a workstation 20 and a therapeutic device 50 operably coupled to the workstation 20. The therapy system 10 may be used with an imaging device 70, which may be operably coupled to a display 72. The patient “P” is shown lying on an operating table 12 with the therapeutic device 50 inserted through a portion of the patient’s femoral artery, although it is contemplated that the therapeutic device 50 may be inserted into any suitable portion of the patient’s vascular network that is in fluid communication with a desired blood vessel for therapy. Although generally described as having one therapeutic device 50, it is envisioned that the therapy system 10 may employ any suitable number of therapeutic devices 50. The therapeutic devices 50 may employ the same or different therapy modalities and be operably coupled to the workstation 20. Further, the therapeutic device 50 may employ a guidewire (not shown) or a guide catheter 58 (FIG. 3) without departing from the scope of the disclosure.

[0024] Continuing with FIG. 1 and with additional reference to FIG. 2, the workstation 20 includes a computer 22, a therapy source 24 (e.g., one or more of an RF generator, a microwave generator, an ultrasound generator, a cryogenic medium source, a chemical source, etc.) operably coupled to the computer 22. In some examples, the computer 22 and therapy source 24 are integrated into a single component and may be referred to as a generator, controller, or console.

[0025] The computer 22 is coupled to a display 26 that is configured to display one or more user interfaces 28. The computer 22 may be a desktop computer or a tower configuration with display 26 or may include a laptop computer or other computing device. The computer 22 includes a processor 30 which executes software stored in a memory 32. The memory 32 maystore one or more applications 34 and / or algorithms 44 to be executed by the processor 30. A network interface 36 enables the workstation 20 to communicate with a variety of other devices and systems via the internet. The network interface 36 may connect the workstation 20 to the Internet via a wired or wireless connection. Additionally, or alternatively, the communication may be via an ad hoc Bluetooth® or wireless network enabling communication with a wide- area network (WAN) and / or a local area network (LAN). The network interface 36 may connect to the Internet via one or more gateways, routers, and network address translation (NAT) devices. The network interface 36 may communicate with a cloud storage system 38, in which further data, image data, and / or videos may be stored. The cloud storage system 38 may be remote from or on the premises of the hospital such as in a control or hospital information technology room. It is envisioned that the cloud storage system 38 could also serve as a host for more robust analysis of acquired images (e.g., fluoroscopic, computed tomography (CT), magnetic resonance imaging (MRI), cone-beam computed tomography (CBCT), etc.), data, etc. (e.g., additional or reinforcement data for analysis and / or comparison). An input module 40 receives inputs from an input device such as a keyboard, a mouse, voice commands, an energy source controller (e.g., a foot pedal or handheld remote-control device) that enables the clinician to initiate, terminate, and optionally, adjust various operational characteristics of the therapy source 24. An output module 42 connects the processor 30 and the memory 32 to a variety of output devices such as the display 26. In embodiments, the display 26 may be a touchscreen display.

[0026] The therapy source 24 may be configured to generate and output one or more of RF energy (monopolar or bipolar), microwave energy, ultrasound energy, cryogenic energy, or chemical ablation medium via semi-automated or automated control algorithm 44 stored on the memory 32 and / or under the control of a clinician. As can be appreciated, many of the therapies listed above change the temperature of the tissue (e.g., increase or decrease the temperature) to achieve the desired denervation of the nerves. The therapy source 24 may be configured to produce a selected modality and magnitude of energy and / or therapy for delivery to the treatment site via the therapeutic device 50, as will be described in further detail hereinbelow. The therapy source 24 may be configured to sense voltage and current (e.g., in the case of RF or other electrical energy) applied to target tissue via the therapeutic device 50. In addition, one or more sensors on the therapeutic device 50 may monitor the temperature of the target tissue or tissue proximate the target tissue, and / or a portion of the therapeutic device 50. Utilizing the sensed voltage and current applied to the tissue, an application 34 on the computer22 may be configured to calculate an impedance of the tissue through which therapeutic energy is transmitted to provide an indication of the status of the tissue. The computer 22 may be configured to output the status to the display 26 on one or more user interfaces 28 to provide a clinician with feedback during navigation of the therapeutic device 50 and during the application of therapy. Further the data collected and used for feedback may also be available for post procedural assessment and analysis by the clinician or other medical personnel.

[0027] FIG. 3 depicts one embodiment of a therapeutic device 50 in accordance with the disclosure. The therapeutic device 50 includes an elongated shaft 52 having a handle (not shown) disposed on a proximal end portion of the elongated shaft 52. The therapeutic device 50 includes an energy delivery assembly 54 on a distal portion of the elongate shaft 52 at which electrodes 56 are located. The elongated shaft 52 of the therapeutic device 50 is configured to be advanced over a guide wire (not shown) within a portion of the patient’s vasculature, such as a femoral artery or other suitable portion of patient’s vascular network that is in fluid communication with the patient’s renal artery. In embodiments, the energy delivery assembly 54 is configured to be transformed from an initial, undeployed configuration having a generally linear profile, to a second, deployed or expanded configuration, where the energy delivery assembly 54 forms a generally spiral and / or helical configuration for delivering energy to a site for application of therapeutic energy or application of stimulation signals at the treatment site. In this manner, when in the second, expanded configuration, the energy delivery assembly 54, and in particular the individual electrodes 56, is pressed against or otherwise contacts the walls of the patient’s vasculature tissue. Although generally described as transitioning to a spiral and / or helical configuration, it is envisioned that the energy delivery assembly 54 may be deployed in other configurations without departing from the scope of the present disclosure. Further, the therapeutic device 50 may be configurable, for example, using one or more pull wires (not shown) to adjust the configuration to promote contact between the electrodes 56 and the wall of the renal artery. As such, the therapeutic device 50 may be capable of being placed in one, two, three, four, or more different configurations depending upon the design needs of the therapeutic device 50 or the location at which therapy is to be applied. Still further, and without departing from the scope of the disclosure, the energy delivery assembly 54 and electrodes 56 may be formed on an exterior of an inflatable balloon, and expandable basket, a lasso, or a pigtail catheter to achieve the placement of the electrodes 56 in contact with the blood vessel wall without departing from the scope of the disclosure. In addition, though generally described as being achieved using a single therapeutic device 50, multiple therapeuticdevices 50 may be employed (e.g., with a separate therapeutic device 50 applying the blocking signal the block neural response).

[0028] As depicted in FIG. 3, the elongated shaft 52 may be configured to be received within a portion of a guide catheter or guide sheath (such as a 6F guide catheter) 58 that is utilized to navigate the therapeutic device 50 to a desired location. In practice, the guide catheter 58 is inserted into an access point such as the femoral artery to gain access to the vascular system. The guide catheter 58 is advanced to the desired location, for example to cannulate a renal artery. A guide wire (not shown) is advanced through the guide catheter 58 and to a location where therapy is to be applied (i.e., beyond a distal end of the guide catheter 58) and into the desired blood vessel (e.g., the renal artery). The therapeutic device 50 is then advanced over the guide wire beyond the end of the guide catheter 58 exposing the electrodes 56 at the location where the therapy is to be applied. The guide wire is then retracted within the therapeutic device 50 and the guide catheter 58. Retraction of the guide wire within the therapeutic device 50 causes the energy delivery assembly 54 of the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (as shown in FIG. 3) with the electrodes 56 contacting the wall of the blood vessel. Though described herein as advancing the therapeutic device 50 beyond the guide catheter 58, in some configurations, the guide catheter 58 may be retracted relative to the therapeutic device 50 to achieve a desired placement of the electrodes 56 in contact with the blood vessel wall. Further, though described herein in connection with the use of a guide wire, the guide wire is not required, and the placement described herein above may be achieved without the use of the guide wire (e.g., with only a guide catheter). The elongated shaft 52 of the therapeutic device 50 may include an aperture (not shown) at a distal end thereof and configured to slidably receive the guidewire over which the therapeutic device 50, either alone or in combination with the guide catheter 58, are advanced. In this manner, the guidewire is utilized to guide the therapeutic device 50 to the target tissue using over-the-wire (OTW) or rapid exchange (RX) techniques, at which point the guide wire may be partially or fully removed from the therapeutic device 50, enabling the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (FIG. 3). As noted elsewhere herein, the therapeutic device 50 may transition from the first, undeployed configuration to the second, deployed configuration automatically (e.g., via a shape memory alloy, etc.) or manually (e.g., via pull wires, guide wire manipulation, etc. that is controlled by the clinician).

[0029] In some embodiments, a pressure sensor 60 may be incorporated into the guide sheath 58 or the shaft elongated 52 for detection of physiological parameters of the patient. In one example the physiological parameter is blood pressure though other parameters may be detected without departing from the scope of the disclosure.

[0030] As illustrated in the figures, the electrodes 56 are disposed in spaced relation to one another along a length of the therapeutic device 50 forming the energy delivery assembly 54. As will be appreciated, these electrodes 56 are in communication with the therapy source 24. The electrodes 56 may deliver therapy independently of one another, simultaneously, selectively, or sequentially. The electrodes 56 may be in electrical communication with a ground pad (not shown) placed on the patient’s skin and electrically connected to the generator and / or stimulator to enable the application of monopolar RF energy for therapy. Additionally or alternatively, therapy may be applied between any desired combination of the electrodes 56, without requiring the use of a ground pad (e.g., bipolar therapy).

[0031] FIG. 4 depicts a variety of data related to the application of therapy from the therapeutic source 24 via the electrodes 56 to the wall of a blood vessel. In each plot of FIG. 4, the data related to each electrode E1-E4 is depicted over time. For example, the plots of FIG. 4 may display data collected over 60 seconds to 2 minutes, or more without departing from the scope of the disclosure. As shown in FIG. 4 there is a plot for each of power, impedance, average temperature and real time temperature. The therapy source 24 either alone or in combination with the computer 22 can detect all of these parameters.

[0032] The data of the multiple plots are informative of the progress of the therapy and the effect of that application of therapy on the electrodes 56 and the tissue around the electrodes. In FIG. 4, electrode 1 (El) does not receive any therapeutic energy. This can be observed in the plot where one of the lines remains essentially constant (e.g., 0 Watts of power or no change in temperature throughout the application of therapy). The other three electrodes in FIG. 4 are receiving therapeutic energy and, as can be observed, express a change in power and change in temperature of electrodes 2-4 (E2-E4) during the application of therapeutic energy. As regards the plot of E4, a high power is achieved and held constant (once achieved) through the full therapy application (e.g., 60 seconds). Similarly, the temperature of electrode E4 increases over approximately the same period as the power increases are observed (e.g., 15-20 seconds). Like the power curve, the plot of the electrode temperature remains substantially constant through the remainder of the therapy application (e.g., about 55 °C).

[0033] In contrast to the plot of E4, the plots of E2 and E3 are very different. With regard to the power, after substantially following the same path as E4 for an initial period (e.g., 10-15 seconds), both E3 and E4 show a drop in power, (e.g., from about 8W to about 4-4.5W). In accordance with this disclosure, the therapy source 24 and computer 22, as part of their safety features, reduce the current flowing through the electrodes 56, and therewith the power applied to the tissue of the blood vessel wall and beyond when a sensed temperature of an electrodes exceeds a threshold. As can be seen with reference to the average temperature plot, E2 reaches a temperature (e.g., about 70 °C) at, for example about 10 seconds, and E3 reaches about the same temperature (e.g., about 70 °C) at, for example about 20 seconds. Achieving these temperatures corresponds with the reduction in power applied to the electrodes. As noted above, the reduction in power is a safety measure implemented during the neuromodulation procedure based on an observed temperature of the electrodes 56. With the reduced power, the temperature drops and remains relatively constant through the remainder of the therapy application, that therapy application being at a reduced power.

[0034] There are a variety of factors that can lead to a rapid rate of change of temperature as observed in the temperature plots of E2 and E3, as compared to E4. For example, there may be low blood flow volume or slow blood flow over the electrode 56. Alternatively, the therapeutic device 50 may be placed in a branch of a main blood vessel. As will be appreciated, because main blood vessels are generally thicker and have more mass, they are slower to heat than branch blood vessels that are generally smaller in mass and thinner. Further, the electrode 56 may be located near an ostium or parenchyma where achieving a successful application of therapy may be difficult to achieve.

[0035] Accordingly, an aspect of the disclosure is directed to a method 100 identifying an environment (e.g., where within the vasculature) a therapeutic device 50 is located. At step 102 an initial dose of therapy, (e.g., apply therapy for 10-20 seconds). While the initial therapy is applied, the rate of change of temperature of each electrode is monitored at step 104. At step 106 a determination is made whether a rate of change of temperature of one or more of the electrodes 56 exceeds a threshold. If at step 106 no rate of change of temperature of any of the electrodes exceeds a threshold (e.g., like electrodes E2 or E3 of FIG. 4), the method proceeds to step 108 where therapy is completed (e.g., until about 60 seconds or some other parameter). As will be appreciated therapy applications may have a time limit, an impedance limit, or another limit without departing from the scope of the disclosure.

[0036] If at step 106 a determination is made that one or more of the electrodes 56 is experiencing a rate of change of temperature in excess of a threshold rate of change the method progresses to step 110. At step 110 a determination is made whether all of the electrodes 56 are experiencing the rate of change of temperature in excess of the threshold. If the determination at step 110 is no, and less than all of the electrodes 56 are experiencing the rate of change of temperature in excess of the threshold, an indicator may be presented (e.g., in user interface 28 on display 26) that there may be an issue with placement of the therapeutic device 50. At step 114, an indicator may be optionally presented regarding which of the electrodes is experiencing the rate of change of temperature in excess of the threshold to assist the clinician in determining a movement of the therapeutic device 50. At step 114 potential causes of the excessive rate of change of temperature may also be presented on the user interface 28. At step 116, a confirmation may be optionally received by the computer 22 that the therapeutic device 50 has been repositioned and the method returns to step 102.

[0037] Where at step 110 all of the electrodes 56 experience a rate of change of temperature in excess of the threshold, at step 118 a request for confirmation of placement of the therapeutic device 50 is in a blood vessel branch may be optionally received (e.g., via user interface 28 on display 26). As described above, the placement and navigation of the therapeutic device 50 is often undertaken with imaging such as ultrasound or fluoroscopy, thus the clinician may already know that the placement of the therapeutic device 50 is in a blood vessel branch (e.g., a renal branch artery as opposed to being placed in the renal artery). Whether automatically or based on the confirmation at step 118, at step 120 the application of the therapy can be completed, but at a reduced power. The reduced power generated by the therapy source 24 and applied via the electrodes 6 to the wall of the blood vessel reduces the temperature of the electrode 56 (e.g., as seen for E2 and E3 in FIG. 4, following reduction of power). At step 122 (following either steps 108 or 120) a determination can be made of the efficacy of the therapy.

[0038] Efficacy of therapy at step 122 can be assessed with reference to a comparison of the power applied to each electrode 56 during the therapy and the rate of change of temperature of that electrode. For example, in a main blood vessel (e.g., renal artery), an efficacious therapy will be one where all electrodes follow the plots of electrode E4 with a high and consistent power (e.g., 8 W) and a rate of change of temperature below a threshold, and never reaching the point where a reduction of power is necessary (e.g., as depicted for electrodes E2 and E3).

[0039] Alternatively, in a branch of the blood vessel (e.g., renal artery branch), an efficacious therapy may be one where all electrodes might initially follow the plot of electrodesE2 or E3. These plots indicate that the electrodes 56 and therewith the blood vessel wall contacting the electrode is experiencing a high rate of change in temperature. Following receipt of confirmation of location of therapeutic device 50 (step 118), or in some instances automatically (optionally following a pause to allow the electrode 56 temperature and the blood vessel wall temperature to return to an ambient temperature), the therapy can be applied at a lower power, and a combination of a consistent low power and a temperature rise similar to that of E4 in FIG. 4 through the remainder of the therapy indicates efficacious therapy application to the branch of the blood vessel.

[0040] A further aspect of the disclosure is depicted in method 200 shown in FIG. 6. In accordance with method 200 at step 202 the user interface 28 may present a clinician an option to identify where the therapeutic device is placed prior to the application of therapy. As an example, the user interface 28 may present two options main or branch blood vessel. Based on the received selection, a power setting for the therapy source 24 is determined (e.g., 8W main blood vessel, 4.5 W branch blood vessel) at step 204. At step 206 the therapy is applied and the rate of change of temperature is monitored. At step 208 a determination is made whether a rate of change of temperature of any electrode 56 exceeds a threshold. If the rate of change of all electrodes 56 does not exceed a threshold the method progresses to step 210 where a determination is made whether the therapy has timed out (e.g., about 60 second). Those of skill in the art will recognize that the end of therapy may additionally or alternatively be identified by achieving a set impedance, impedance change, or other end point. If the therapy has not timed out, therapy continues 212 and the rate of change of temperature continues to be monitored at step 208. When the therapy times out at step 210 the method progresses to step 214 and a determination of the efficacy of the therapy is determined. At step 216 an indicator of efficacy is displayed on the user interface 28.

[0041] If at any time during method 200 at step 208 the rate of change of temperature exceeds a threshold, the method proceeds to steps 218-222 which substantially correspond to steps 112-116 described above in connection with method 100, and thus not repeated here.

[0042] Fig. 7 depicts a plot in accordance with aspects of the disclosure described herein. Along the X-axis is a measurement of the rate of change of the temperature in degrees C per second of the application of therapy. Box 302 represents a high-power successful therapy window as might be observed from a successful application of therapy to a main blood vessel (e.g., the renal artery. The rate of change of temperature remains relatively low (similar to the plot of E4 in FIG.4). Further, a high and consistent power (e.g., about 8W) is achieved for theduration of the therapy application. Box 304 represents a low-power successful therapy window as might be observed from successful application of therapy to a branch blood vessel. Again the electrodes 56 all show a relatively low rate of change of temperature and a consistent low power (e.g., about 4-4.5 W.

[0043] Box 306 represents a poor or incomplete therapy window. During the application of therapy (e.g., methods 100 or 200) if one but not all of the electrodes 56 are found to have a high rate of change of temperature and a relatively low power (e.g., as shown for electrodes E2 and E3 of FIG. 4), the therapy application may be incomplete. As noted elsewhere herein, where less than all of the electrodes 56 are plotted in the box 306, this may be due to placement of the therapeutic device (e.g., at or near ostia or partially in the blood vessel branch and partially in the main blood vessel). Alternatively, if all electrodes 56 have their power vs rate of temperature change plotted in box 306 and therapy is completed to the therapy time-out (e.g., step 210) the efficacy determination may include an indication that the patient is suffering from low blood flow often associated with end stage kidney disease.

[0044] Accordingly, employing the methods and systems described herein a determination can be made of the environment at which the electrodes 56 of the therapeutic device 50 are placed. Further an assessment can be made of the efficacy of the therapy, and in some instances a determination can be made regarding the disease state of the patient.

[0045] Heretofore, the therapeutic device 50 has been primarily described in connection with a shape memory construction where exit from a guide catheter 58 frees the shape memory alloy to achieve a desired spiral and / or helical shape of the distal end and place the electrodes 56 against the blood vessel walls. However, the present disclosure is not so limited and the therapeutic device 50 may be formed such that the electrodes are placed on a balloon or other mechanism to achieve the desired contact with the blood vessel walls without departing from the scope of the disclosure.

[0046] Although described generally hereinabove, it is envisioned that the memory 32 may include any non-transitory computer-readable storage media for storing data and / or software including instructions that are executable by the processor 30 and which control the operation of the workstation 20 and, in some embodiments, may also control the operation of the therapeutic device 50. In an embodiment, memory 32 may include one or more storage 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 may include one or more massstorage devices connected to the processor 30 through a mass storage controller (not shown) and a communications bus (not shown).

[0047] The description of computer-readable media contained herein refers to solid-state storage. It should be appreciated by those skilled in the art that computer-readable storage media can be any available media that can be accessed by the processor 30. That is, computer readable storage media may include non-transitory, volatile, and non-volatile, removable, and nonremovable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules or other data. For example, computer-readable storage media may include RAM, ROM, EPROM, EEPROM, flash memory or other solid-state memory technology, CD-ROM, DVD, Blu-Ray or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which may be used to store the desired information, and which may be accessed by the workstation 20.EXAMPLES

[0048] The disclosure is further described in connection with the following examples in which:

[0049] Example 1. A system for denervation of nerves of a blood vessel including a catheter configured to be navigated within a blood vessel of a patient, the catheter comprising at least one therapeutic element configured to apply a therapy to nerves adjacent the blood vessel, a therapy source in communication with the at least one therapeutic element and configured to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element, and a computing device including a processor and memory, the memory storing therein instructions that, when executed by the processor, cause the processor to cause the therapy source to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element, detect a rate of change of temperature associated with the at least one therapeutic element, and determine an environment of the at least one therapeutic element based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element.

[0050] Example 2. The system of example 1, wherein the instructions when executed by the processor, cause the processor to: determine an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element; and output, for display at a user interface of the computing device, an indicator of efficacy of the therapy.

[0051] Example 3. The system of example 1 or 2, wherein the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy.

[0052] Example 4. The system of any one of examples 1-3, wherein the therapeutic element comprises a plurality of electrodes or at least one ultrasound transducer.

[0053] Example 5. The system of example 4, wherein the instructions, when executed by the processor, cause the processor to determine a corresponding environment for each of the plurality of electrodes or at least one ultrasound transducer.

[0054] Example 6. The system of any one of examples 1-5, wherein the instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with the at least one therapeutic element exceeds a threshold value; and in response to the determination that the rate of change of temperature exceeds the threshold value, cause the therapy source to reduce a power of the therapeutic energy.

[0055] Example 7. The system of any one of examples 1-6, wherein the memory further stores therein instructions that, when executed by the processor, cause the processor to receive via a user interface a confirmation that the at least one therapeutic element is located within a blood vessel branch.

[0056] Example 8. The system of any of examples 4 or 5, wherein the instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with less than all of the electrodes or at least one ultrasound transducers exceed a threshold value; and output for display on a user interface of the computing device an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer.

[0057] Example 9. The system of example 8, wherein the instructions, when executed by the processor, cause the processor to output for display on the user interface of the computing device an indicator of which electrode of the plurality of electrodes or the at least one ultrasound transducer experienced a rate of change of temperature in excess of the threshold value.

[0058] Example 10. A system for denervation of nerves of a blood vessel comprising: a catheter configured to be navigated within a blood vessel of a patient, the catheter comprising at least one therapeutic element configured to apply a therapy to nerves adjacent the blood vessel; a therapy source in communication with the at least one therapeutic element and configured to generate therapeutic energy and output the therapeutic energy to the at least onetherapeutic element; and a computing device including a processor and memory, the memory storing therein instructions that, when executed by the processor, cause the processor to: receive a selection of therapeutic element placement; set a power of the therapeutic energy of the therapy source based on the selection of therapeutic element placement; cause the therapy source to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; and detect a rate of change of temperature associated with the at least one therapeutic element.

[0059] Example 11. The system of example 10, wherein the instructions when executed by the processor, cause the processor to: determine an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with at least one therapeutic element; and output, for display at a user interface of the computing device an indicator of efficacy of the therapy.

[0060] Example 12. The system of 10 or 11, wherein the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy.

[0061] Example 13. The system of any one of examples 10-12, wherein the therapeutic element comprises a plurality of electrodes or at least one ultrasound transducer.

[0062] Example 14. The system of example 13, wherein the instructions when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with one or more of the electrodes or at least one ultrasound transducer exceeds a threshold value, and output for display on a user interface of the computing device an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer.

[0063] Example 15. The system of example 14, wherein the instructions when executed by the processor cause the processor to output for display on the user interface of the computing device an indicator of which electrode of the plurality of electrodes or the at least one ultrasound transducer experienced a rate of change of temperature in excess of the threshold value.

[0064] Example 16. A method of identifying an environment of a therapeutic device, comprising: generating a therapeutic energy at a therapy source; delivering the therapeutic energy to a therapeutic element for application to a blood vessel wall; determining a rate of change of temperature associated with the therapeutic element; and determining anenvironment of the therapeutic element based at least in part on the detected rate of change of temperature associated with the therapeutic element.

[0065] Example 17. The method of example 16, further comprising determining an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with the therapeutic element: and displaying at a user interface of a computing device an indicator of efficacy of the therapy.

[0066] Example 18. The method of examples 16 or 17, wherein the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy.

[0067] Example 19. The method of any of examples 16-18, wherein the therapeutic element comprises a plurality of electrodes or at least one ultrasound transducer and further comprising: determining that the rate of change of temperature associated with all of the electrodes or ultrasound transducers exceeds a threshold value; and reducing a power of the therapeutic energy output by the therapy source.

[0068] Example 20. The method of any of examples 16-18, wherein the therapeutic element is a plurality of electrodes or ultrasound transducers and further comprising: determining that the rate of change of temperature associated with less than all of the electrodes or at least one ultrasound transducer exceed a threshold value; and displaying on a user interface an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer.

[0069] While several embodiments of the disclosure have been shown in the drawings, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise. Therefore, the above description should not be construed as limiting, but merely as exemplifications of embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

Claims

CLAIMS1. A system for denervation of nerves of a blood vessel comprising: a catheter configured to be navigated within a blood vessel of a patient, the catheter comprising at least one therapeutic element configured to apply a therapy to nerves adjacent the blood vessel; a therapy source in communication with the at least one therapeutic element and configured to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; and a computing device including a processor and memory, the memory storing therein instructions that, when executed by the processor, cause the processor to: cause the therapy source to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; detect a rate of change of temperature associated with the at least one therapeutic element; and determine an environment of the at least one therapeutic element based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element.

2. The system of claim 1, wherein the instructions when executed by the processor, cause the processor to: determine an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with the at least one therapeutic element; and output, for display at a user interface of the computing device, an indicator of efficacy of the therapy.

3. The system of claim 1 or 2, wherein the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy.

4. The system of any one of claims 1-3, wherein the therapeutic element comprises a plurality of electrodes or at least one ultrasound transducer.

5. The system of claim 4, wherein the instructions, when executed by the processor, cause the processor to determine a corresponding environment for each of the plurality of electrodes or at least one ultrasound transducer.

6. The system of any one of claims 1-5, wherein the instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with the at least one therapeutic element exceeds a threshold value; and in response to the determination that the rate of change of temperature exceeds the threshold value, cause the therapy source to reduce a power of the therapeutic energy.

7. The system of any one of claims 1-6, wherein the memory further stores therein instructions that, when executed by the processor, cause the processor to receive via a user interface a confirmation that the at least one therapeutic element is located within a blood vessel branch.

8. The system of any of claims 4 or 5, wherein the instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature associated with less than all of the electrodes or at least one ultrasound transducers exceed a threshold value; and output for display on a user interface of the computing device an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer.

9. The system of claim 8, wherein the instructions, when executed by the processor, cause the processor to output for display on the user interface of the computing device an indicator of which electrode of the plurality of electrodes or the at least one ultrasound transducer experienced a rate of change of temperature in excess of the threshold value.

10. A system for denervation of nerves of a blood vessel comprising:a catheter configured to be navigated within a blood vessel of a patient, the catheter comprising at least one therapeutic element configured to apply a therapy to nerves adjacent the blood vessel; a therapy source in communication with the at least one therapeutic element and configured to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; and a computing device including a processor and memory, the memory storing therein instructions that, when executed by the processor, cause the processor to: receive a selection of therapeutic element placement; set a power of the therapeutic energy of the therapy source based on the selection of therapeutic element placement; cause the therapy source to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; and detect a rate of change of temperature associated with the at least one therapeutic element.

11. The system of claim 10, wherein the instructions when executed by the processor, cause the processor to: determine an efficacy of the therapy based at least in part on the detected rate of change of temperature associated with at least one therapeutic element; and output, for display at a user interface of the computing device an indicator of efficacy of the therapy.

12. The system of 10 or 11, wherein the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, or an ultrasound therapy.

13. The system of any one of claims 10-12, wherein the therapeutic element comprises a plurality of electrodes or at least one ultrasound transducer.

14. The system of claim 13, wherein the instructions when executed by the processor, cause the processor to:determine that the rate of change of temperature associated with one or more of the electrodes or at least one ultrasound transducer exceeds a threshold value, and output for display on a user interface of the computing device an indicator of a potential placement issue of at least one of the plurality of electrodes or at least one ultrasound transducer.

15. The system of claim 14, wherein the instructions when executed by the processor cause the processor to output for display on the user interface of the computing device an indicator of which electrode of the plurality of electrodes or the at least one ultrasound transducer experienced a rate of change of temperature in excess of the threshold value.

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