Ablation success quantification

Abstract

A system and method for denervation of nerves of a blood vessel including a catheter for navigation within a blood vessel, 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, cause the processor to cause the therapy source to generate the therapeutic energy, determine a rate of change of temperature associated with the therapeutic element while the therapeutic element is outputting the therapeutic energy, and determine efficacy of the therapy based on a comparison of a power of the therapeutic energy output to the therapeutic element and a rate of change of a temperature associated with the therapeutic element.

Description

ABLATION SUCCESS QUANTIFICATION

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 653,435, filed May 30, 2024, the entire content of which is incorporated herein by reference.Technical Field

[0002] This disclosure relates to systems and methods evaluating an ablation within a blood vessel.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 general 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, cause the processor to: cause the therapy source to generate the therapeutic energy; determine a rate of change of temperature associated with the at least one therapeutic element while the at least one therapeutic element is outputting the therapeutic energy; and determine efficacy of the therapy based on a comparison of a power of the therapeutic energy output to the at least one therapeutic element and a rate of change of a 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.

[0006] Implementations may include one or more of the following features. The system where the instructions, when executed, cause the processor to output for display at a display device an indicator of efficacy of the therapy based at least in part of the 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 rate of change of temperature associated with each electrode or ultrasound transducer and a corresponding power applied to each electrode or ultrasound transducer. The instructions, when executed by the processor, cause the processor determine that the therapy is efficacious when the power output to the at least one therapeutic element is substantially constant after achieving a desired level. The instructions, when executed by the processor, cause the processor to determine that the therapy is efficacious when a rate of change of temperature of therapeutic element remains below a threshold value. The instructions, when executed by the processor, cause the processor to determine that the therapy is not efficacious when a rate of change of temperature of the at least one therapeutic element exceeds a threshold value or a power applied to the at least one therapeutic element drops during application of the therapy. The instructions, when executed by the processor, cause the processor to output, for display on a user interface of the computing device, an indicator of a not efficacious therapy by the at least one therapeutic element. The system may include receiving via a user interface a selection of a placement of the catheter within a main blood vessel or 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] A further 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: cause the therapy source to generate therapeutic energy and output the therapeutic energy to the at least one therapeutic element; monitor a power of the therapeutic energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeutic element due at least in part to the therapeutic energy; cause the therapy source to generate confirmation energy; monitor a power of the confirmation energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeutic element due at least in part to the confirmation energy; and determine efficacy of the therapy based at least in part on the rate of change of temperature of the at least one therapeutic element due at least in part to the confirmation energy. 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 output, for display on a user interface of the computing device, an indicator of the 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 of the at least one therapeutic element caused by application of the confirmation energy and the power of the confirmation energy is different than the rate of change of temperature of the at least one therapeutic element caused by application of the therapeutic energy and the power of the therapeutic energy; and display an indicator on a user interface of an efficacious application of therapy. The instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature of the at least one therapeutic element caused by application of the confirmation energy and the power of theconfirmation energy is substantially the same as the rate of change of temperature of the at least one therapeutic element caused by application of the therapeutic energy and the power of the therapeutic energy; and display an indicator on a user interface of an inefficacious application of therapy. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium.

[0009] Still a further aspect of the disclosure is a method of assessing efficacy of a denervation therapy. The method includes generating a therapeutic energy at a therapy source; delivering the therapeutic energy to at least one therapeutic element for application to nerves adjacent a blood vessel, determining a rate of change of temperature associated with of the at least one therapeutic element while the at least one therapeutic element is outputting the therapeutic energy, and determining a power of the therapeutic energy output to the at least one therapeutic element, and determining an efficacy of the therapy based on a comparison of the power of the therapeutic energy output to the therapeutic element and a rate of change of a 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 where 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 is a plurality of electrodes or ultrasound transducers and may include: determining that the therapy is efficacious when the power output to the at least one therapeutic element is substantially constant after achieving a desired level, or determining that the therapy is efficacious when a rate of change of temperature of the therapeutic element remains below a threshold value. The therapeutic element is a plurality of electrodes or ultrasound transducers and may include: causing the therapy source to generate confirmation energy; monitoring a power of the confirmation energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeutic element due at least in part to the confirmation energy; determining that the rate of change of temperature of the therapeutic element caused by the application of the confirmation energy and the power of the confirmation energy is different than the rate of change of temperature of the therapeutic element caused by the application of the therapeutic energy and the power of the therapeutic energy; and displaying on a user interface of a computing device an indicator of an efficacious therapy.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 within a blood vessel, 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, cause the processor to cause the therapy source to generate the therapeutic energy, determine a rate of change of temperature associated with the therapeutic element while the therapeutic element is outputting the therapeutic energy, and determine efficacy of the therapy based on a comparison of a power of the therapeutic energy output to the therapeutic element and a rate of change of a temperature associated with the 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;

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

[0020] FIG. 8 is a graphic representation of two plots representing the methodology of FIG. 6.DETAILED DESCRIPTION

[0021] This disclosure describes 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 describe ablation and denervation of unmyelinated nerve fibers in and around blood vessel walls and other luminal tissues. In particular, this disclosure describes systems and methods that provide post-procedural assessment of the application of therapy (e.g., denervation or neuromodulation) to a wall of the blood vessel.

[0022] 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 moreanatomical lumens, e.g., in the renal arteries and the common hepatic artery, or any other combination of two or more anatomical lumens, either simultaneously or sequentially. In addition, the systems, devices, and methods described herein may be useful in conjunction with neuromodulation (e.g., denervation) within a body lumen other than a vessel, for extravascular neuromodulation and / or for use in conjunction with therapies other than neuromodulation. Still further while generally contemplated that the locations described above are to be navigated to percutaneously, for example via the femoral artery, the therapeutic devices described herein may also be placed laparoscopically placed in or near one or more of the above-identified blood vessels, or another luminal tissue without departing from the scope of the present disclosure.

[0023] 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.

[0024] 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.

[0025] 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 source24 are integrated into a single component and may be referred to as a generator, controller, or console.

[0026] 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 may store one or more applications 34 and / or algorithms 44 to be executed by the processor 30. A network interface 36 enables the workstation 20 to communicate with a variety of other devices and systems via the internet. The network interface 36 may connect the workstation 20 to the Internet via a wired or wireless connection. Additionally, or alternatively, the communication may be via an ad hoc Bluetooth® or wireless network enabling communication with a wide- area network (WAN) and / or a local area network (LAN). The network interface 36 may connect to the Internet via one or more gateways, routers, and network address translation (NAT) devices. The network interface 36 may communicate with a cloud storage system 38, in which further data, image data, and / or videos may be stored. The cloud storage system 38 may be remote from or on the premises of the hospital such as in a control or hospital information technology room. It is envisioned that the cloud storage system 38 could also serve as a host for more robust analysis of acquired images (e.g., fluoroscopic, computed tomography (CT), magnetic resonance imaging (MRI), cone-beam computed tomography (CBCT), etc.), data, etc. (e.g., additional or reinforcement data for analysis and / or comparison). An input module 40 receives inputs from an input device such as a keyboard, a mouse, 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.

[0027] 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 thetreatment 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 computer 22 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.

[0028] 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 ofthe 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 therapeutic devices 50 may be employed (e.g., with a separate therapeutic device 50 applying the blocking signal the block neural response).

[0029] As depicted in FIG. 3, the elongated shaft 52 may be configured to be received within a portion of a guide catheter or guide sheath (such as a 6F guide catheter) 58 that is utilized to navigate the therapeutic device 50 to a desired location. In practice, the guide catheter 58 is inserted into an access point such as the femoral artery to gain access to the vascular system. The guide catheter 58 is advanced to the desired location, for example to cannulate a renal artery. A guide wire (not shown) is advanced through the guide catheter 58 and to a location where therapy is to be applied (i.e., beyond a distal end of the guide catheter 58) and into the desired blood vessel (e.g., the renal artery). The therapeutic device 50 is then advanced over the guide wire beyond the end of the guide catheter 58 exposing the electrodes 56 at the location where the therapy is to be applied. The guide wire is then retracted within the therapeutic device 50 and the guide catheter 58. Retraction of the guide wire within the therapeutic device 50 causes the energy delivery assembly 54 of the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (as shown in FIG. 3) with the electrodes 56 contacting the wall of the blood vessel. Though described herein as advancing the therapeutic device 50 beyond the guide catheter 58, in some configurations, the guide catheter 58 may be retracted relative to the therapeutic device 50 to achieve a desired placement of the electrodes 56 in contact with the blood vessel wall. Further, though described herein in connection with the use of a guide wire, the guide wire is not required, and the placement described herein above may be achieved without the use of the guide wire (e.g., with only a guide catheter). The elongated shaft 52 of the therapeutic device 50 may include an aperture (not shown) at a distal end thereof and configured to slidably receive the guidewire over which the therapeutic device 50, either alone or in combination with the guide catheter 58, are advanced. In this manner, the guidewire is utilized to guide the therapeutic device 50 to the target tissue using over-the-wire (OTW) or rapid exchange (RX) techniques, at which point the guide wire may be partially or fullyremoved from the therapeutic device 50, enabling the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (FIG. 3). As noted elsewhere herein, the therapeutic device 50 may transition from the first, undeployed configuration to the second, deployed configuration automatically (e.g., via a shape memory alloy, etc.) or manually (e.g., via pull wires, guide wire manipulation, etc. that is controlled by the clinician).

[0030] 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.

[0031] 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).

[0032] 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.

[0033] 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 regardsthe 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).

[0034] 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 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.

[0035] 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.

[0036] Accordingly, an aspect of the disclosure is directed to a method 100 of assessing an application of therapy within a blood vessel. At step 102, following placement of the therapeutic device within a desired blood vessel therapy is applied. While the therapy is applied, the rate of change of temperature of each electrode is monitored at step 104. At step 106, and also while therapy is applied the power output from the therapy source 24 to each of the electrodes 56 is monitored. At step 108 the therapy reaches its end point. The end pointmay be reaching a time limit (e.g., 60 seconds), reaching an impedance threshold, an applied power threshold, or another end point. At step 110 a determination is made whether a rate of change of temperature of one or more of the electrodes 56 exceeds a threshold and whether a power applied to each electrode remains above a threshold. If at step 110 the determination is yes, then at step 112 an indicator is displayed that the application of therapy was efficacious. Efficacious therapy may be, for example, one where all four electrodes 56 (E1-E4) have temperature change and power plots similar to E4 in FIG. 4. If, however, at step 110 the determination is no, then at step 114 an indicator is displayed that the application of therapy was not efficacious. A non-efficacious therapy or incomplete therapy is one where one or more of the electrodes 56 have temperature and power plots similar to E2 or E3, while other electrodes have plots similar to E4 of FIG. 4.

[0037] Optionally, at step 116 an indicator may be displayed regarding which electrode 56 experienced the rate of change of temperature in excess of the threshold or a reduction in power below a threshold. Again optionally, the placement of therapeutic device 50 may be adjusted and confirmation of the adjustment may be received at step 118, and the method returns to step 102. This may be repeated until an efficacious therapy is applied or a clinician determines to stop therapy.

[0038] A further optional step may be employed prior to step 102. Prior to the initiation of therapy an indicator of placement of the therapeutic device 50 may be received at step 101 (e.g., via an application 34 on the computer 22). For example, a clinician may identify the placement of the therapeutic device 50 within either a main blood vessel (e.g., renal artery) or a blood vessel branch (e.g., renal branch artery). The indication of placement may set a power to be generated by the therapy source 24 (e.g., 8W main blood vessel, 4.5 W branch blood vessel), or may identify an expected drop in power (e.g., average power) during the application of the therapy that can be employed in step 110 in assessing the efficacy of the therapy. Where for example, the location of placement of the therapeutic device 50 is within the blood vessel branch, all electrodes 56 may have temperature change and power plots similar to E2 or E3 of FIG. 4. As long as all of the electrodes 56 experience the same or substantially the same rate of change of temperature and power plots, the therapy can still be determined efficacious at step 110.

[0039] The application of therapy necessarily creates changes in the tissue to which the therapy is applied. This change in the tissue results in changes in the manner in which energy is transferred from the electrodes 56 to the tissue (e.g., of the wall of a blood vessel).Accordingly, in a further aspect of the disclosure a comparison can be made regarding rate of change in temperature and power for untreated tissue to treated tissue. Where there is difference between a during therapy rate of change in temperature and power and a post therapy rate of change in temperature and power during secondary (short duration) application of therapeutic energy, the therapy can be determined efficacious. In contrast, if they are the same, then the therapy can be determined to be not efficacious.

[0040] An example of a method 200 for confirmation of efficacy of therapy is depicted in in FIG. 6. In accordance with method 200 at step 202, after placement of the therapeutic device therapy is initiated. This may be achieved via receipt of an input on the user interface 28 of the display 26, alternatively a foot pedal (not shown), a button on the therapeutic device 50 or another other therapy initiating mechanism. At step 204 a rate of change of temperature of each electrode is monitored. The rate of change of temperature data may be stored in the memory 32 for later use in method 200. At step 206 the power applied to each electrode is monitored and again the power data may be stored in the memory 32. At step 208, reaches its end point (e.g., time end point, impedance endpoint, or another endpoint). At step 210 confirmation energy is applied. The confirmation energy is for example the same energy (power, voltage, current, etc.) as the therapy energy applied at step 202, however the confirmation energy is only applied for a short duration (e.g., about 10 seconds). At step 212 the rate of change of temperature of the electrodes 56 is monitored and the rate of change of temperature data is stored in the memory 32. At step 314 the power applied to each electrode 56 is monitored and again the power data is stored in the memory 32. At step 215 the endpoint of the confirmation energy application is reached (e.g., the conclusion of 10 seconds). At step 216 a comparison of the rate of change of temperature data (step 204) and power data (step 206) from the therapy to the rate of change of temperature data (step 212) and power data (step 214) from the confirmation energy application. If there is a difference, indicating that the tissue of the blood vessel have been altered as a result of the therapy, an indicator of efficacy of the therapy can be displayed in the user interface 28 at step 218. As will be appreciated, in some instances the difference or the magnitude of the difference determined at step 218 must exceed some threshold to indicate an efficacious therapy. If there is no change, or insufficient change at step 216 at step 220 an indicator may be presented on the user interface 28 that that therapy was not efficacious. As with method 100, at steps 222 an indicator of the relevant electrode may be optionally presented on the user interface 28 and following receipt (e.g., via the user interface 28) of repositioning of the therapeutic device 50 the method 200 returns to step 202. Steps 222and 224 are described in greater detail with regard to method 100 and in the interest of brevity are not further described here. The method 200 may be repeated until an efficacious therapy is achieved (step 218) or until the clinician determines that further application of therapy is inappropriate.

[0041] 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 °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) at less than about 2°C / s. Further, a high and consistent power (e.g., more than 6W) is achieved for the duration 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 (e.g., less than about 2°C / s) and a consistent low power (e.g., about 4-4.5 W).

[0042] Box 306 represents a poor or incomplete therapy window. During the application of therapy (e.g., method 100) 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).

[0043] FIG. 8 is a graphic representation of the method 200. In FIG. 8, a first plot 402 of power applied during therapy vs a rate of change of temperature (temp slope). A data point 404 is a representation of the data collected at steps 204 and 206 (or 204, 206) above. In this instance, the data point falls within the box 302 of FIG. 7, and thus likely an efficacious application of therapy with high power (e.g., > 6W) and low rate of change in temperature (e.g., < 2°C / s). Though only a single data point 404 is shown in plot 402 which may represent an average value of all electrodes 56, alternatively multiple datapoints 404 (e.g., one for each electrode 56) may be plotted individually to confirm that the data for all electrodes 56 fall within box 302 and the therapy was likely successful (e.g., in connection with method 100 and step 110).

[0044] However, in connection with method 200, after the application of confirmation energy is applied at step 210. In plot 406 of FIG. 8 datapoints 408 and 410 are presented. Theplot 406 represents the power of the confirmation energy vs a rate of change of temperature (temp slope). Datapoint 408 represents a power and rate of change of temperature during application of the confirmation energy that largely coincides with or is similar to that from the application of the therapy (shown in plot 402). Thus, the data point 408 is an indicator (step 216) that the therapy was not efficacious or insufficiently efficacious. In contrast, the data point 410 depicts a rate of change of temperature and a power that is different from that observed for data point 404. Thus, data point 410 indicates that the therapy was efficacious as the characteristics of the tissue to which the therapy was applied has sufficiently changed. In plot 406 at data point 410 the rate of change of temperature is greater than that observed in generation of data point 404 and a power that is less than that of data point 404. However, datapoint 410 is merely an example, and an actual difference confirming a successful therapy may not require both a lower power and higher rate of change of temperature. Further, and as noted above, the magnitude of the difference in the data points 404 and 410 may vary and still indicate a successful application of therapy.

[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 mass storage 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 readablestorage 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, cause the processor to: cause the therapy source to generate the therapeutic energy; determine a rate of change of temperature associated with the at least one therapeutic element while the at least one therapeutic element is outputting the therapeutic energy; and determine efficacy of the therapy based on a comparison of a power of the therapeutic energy output to the at least one therapeutic element and a rate of change of a temperature associated with the therapeutic element.

[0050] Example 2. The system of example 1, wherein the instructions, when executed, cause the processor to output for display at a display device an indicator of efficacy of the therapy based at least in part of the 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 rate of change of temperatureassociated with each electrode or ultrasound transducer and a corresponding power applied to each electrode or 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 determine that the therapy is efficacious when the power output to the at least one therapeutic element is substantially constant after achieving a desired level.

[0055] Example 7. The system of any one of examples 1-6, wherein the instructions, when executed by the processor, cause the processor to determine that the therapy is efficacious when a rate of change of temperature of therapeutic element remains below a threshold value.

[0056] Example 8. The system of any one of examples 1-7, wherein the instructions, when executed by the processor, cause the processor to determine that the therapy is not efficacious when a rate of change of temperature of the at least one therapeutic element exceeds a threshold value or a power applied to the at least one therapeutic element drops during application of the therapy.

[0057] Example 9. The system of example 8, wherein the instructions, when executed by the processor, cause the processor to output, for display on a user interface of the computing device, an indicator of an not efficacious therapy by the at least one therapeutic element.

[0058] Example 10. The system of any one of examples 1-9, further comprising receiving via a user interface a selection of a placement of the catheter within a main blood vessel or a blood vessel branch.

[0059] Example 11. 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; monitor a power of the therapeutic energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeutic element due at least in part to the therapeutic energy; cause the therapy source to generate confirmation energy; monitor a power of the confirmation energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeuticelement due at least in part to the confirmation energy; and determine efficacy of the therapy based at least in part on the rate of change of temperature of the at least one therapeutic element due at least in part to the confirmation energy.

[0060] Example 12. The system of example 11, wherein the instructions, when executed by the processor, cause the processor to output, for display on a user interface of the computing device, an indicator of the efficacy of the therapy.

[0061] Example 13. The system of example 11 or 12, 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.

[0062] Example 14. The system of any one of examples 11-13, wherein the therapeutic element comprises a plurality of electrodes or at least one ultrasound transducer.

[0063] Example 15. The system of any one of examples 11-14, wherein the instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature of the at least one therapeutic element caused by application of the confirmation energy and the power of the confirmation energy is different than the rate of change of temperature of the at least one therapeutic element caused by application of the therapeutic energy and the power of the therapeutic energy; and display an indicator on a user interface of an efficacious application of therapy.

[0064] Example 16. The system of any of examples 11-14, wherein the instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature of the at least one therapeutic element caused by application of the confirmation energy and the power of the confirmation energy is substantially the same as the rate of change of temperature of the at least one therapeutic element caused by application of the therapeutic energy and the power of the therapeutic energy; and display an indicator on a user interface of an inefficacious application of therapy.

[0065] Example 17. A method of assessing efficacy of a denervation therapy, including: generating a therapeutic energy at a therapy source; delivering the therapeutic energy to at least one therapeutic element for application to nerves adjacent a blood vessel; determining a rate of change of temperature associated with of the at least one therapeutic element while the at least one therapeutic element is outputting the therapeutic energy; and determining a power of the therapeutic energy output to the at least one therapeutic element; and determining an efficacy of the therapy based on a comparison of the power of the therapeutic energy output to thetherapeutic element and a rate of change of a temperature associated with the therapeutic element.

[0066] Example 18. The method of example 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 example 17-18, wherein the therapeutic element is a plurality of electrodes or ultrasound transducers and further including: determining that the therapy is efficacious when the power output to the at least one therapeutic element is substantially constant after achieving a desired level, or determining that the therapy is efficacious when a rate of change of temperature of the therapeutic element remains below a threshold value.

[0068] Example 20. The method of claim 17, wherein the therapeutic element is a plurality of electrodes or ultrasound transducers and further comprising: causing the therapy source to generate confirmation energy; monitoring a power of the confirmation energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeutic element due at least in part to the confirmation energy; determining that the rate of change of temperature of the therapeutic element caused by the application of the confirmation energy and the power of the confirmation energy is different than the rate of change of temperature of the therapeutic element caused by the application of the therapeutic energy and the power of the therapeutic energy; and displaying on a user interface of a computing device an indicator of an efficacious therapy.

[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, cause the processor to: cause the therapy source to generate the therapeutic energy; determine a rate of change of temperature associated with the at least one therapeutic element while the at least one therapeutic element is outputting the therapeutic energy; and determine efficacy of the therapy based on a comparison of a power of the therapeutic energy output to the at least one therapeutic element and a rate of change of a temperature associated with the therapeutic element.

2. The system of claim 1, wherein the instructions, when executed, cause the processor to output for display at a display device an indicator of efficacy of the therapy based at least in part of the 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 rate of change of temperatureassociated with each electrode or ultrasound transducer and a corresponding power applied to each electrode or ultrasound transducer.

6. The system of any one of claims 1-5, wherein the instructions, when executed by the processor, cause the processor determine that the therapy is efficacious when the power output to the at least one therapeutic element is substantially constant after achieving a desired level.

7. The system of any one of claims 1-6, wherein the instructions, when executed by the processor, cause the processor to determine that the therapy is efficacious when a rate of change of temperature of therapeutic element remains below a threshold value.

8. The system of any one of claims 1-7, wherein the instructions, when executed by the processor, cause the processor to determine that the therapy is not efficacious when a rate of change of temperature of the at least one therapeutic element exceeds a threshold value or a power applied to the at least one therapeutic element drops during application of the therapy.

9. The system of claim 8, wherein the instructions, when executed by the processor, cause the processor to output, for display on a user interface of the computing device, an indicator of an not efficacious therapy by the at least one therapeutic element.

10. The system of any one of claims 1-9, further comprising receiving via a user interface a selection of a placement of the catheter within a main blood vessel or a blood vessel branch.

11. 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; monitor a power of the therapeutic energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeutic element due at least in part to the therapeutic energy; cause the therapy source to generate confirmation energy; monitor a power of the confirmation energy output to the at least one therapeutic element; monitor a rate of change of temperature of the at least one therapeutic element due at least in part to the confirmation energy; and determine efficacy of the therapy based at least in part on the rate of change of temperature of the at least one therapeutic element due at least in part to the confirmation energy.

12. The system of claim 11, wherein the instructions, when executed by the processor, cause the processor to output, for display on a user interface of the computing device, an indicator of the efficacy of the therapy.

13. The system of claim 11 or 12, 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.

14. The system of any one of claims 11-13, wherein the therapeutic element comprises a plurality of electrodes or at least one ultrasound transducer.

15. The system of any one of claims 11-14, wherein the instructions, when executed by the processor, cause the processor to: determine that the rate of change of temperature of the at least one therapeutic element caused by application of the confirmation energy and the power of the confirmation energy is different than the rate of change of temperature of the at least one therapeutic element caused by application of the therapeutic energy and the power of the therapeutic energy; and display an indicator on a user interface of an efficacious application of therapy.

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