IRRIGATED ABLATED CATHETER TEMPERATURE ESTIMATES USING IMPEDANCE DATA
[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63/541,387, filed September 29, 2023, the entire content of which is incorporated herein by reference.
Technical Field
[0002] This disclosure relates to systems and methods assessing efficacy of an ablation procedure. In particular aspects, the disclosure is directed to methods and systems for denervating nerves and providing feedback to physicians regarding efficacy of the denervation therapy.
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 likely 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 a renal denervation procedure, a clinician delivers stimuli or energy, such as radiofrequency, ultrasound, cooling, or other energy to a treatment site to reduce activity of nerves surrounding a blood vessel. The stimuli or energy delivered to the treatment site may provide various therapeutic effects through alteration of sympathetic nerve activity.
[0005] In other ablation procedures, irrigated catheters offer an advantage when it is necessary to deliver more power to achieve the target lesion size. However, the presence of irrigation fluid (typically injected at room temperature, though might be cooler) means that the temperature measured, for example by an electrode on the catheter is often below body temperature. Thus, the measured temperature is not representative of the actual temperature of the tissue receiving the ablation energy. In non-irrigated catheters, the electrode temperature has been used to provide information regarding the safety of the procedure. With the application of energy to the tissue, if tissue temperatures get excessive there can be damage over and above that intended to perform the denervation. Irrigation, however, eliminates the utility of considering the electrode temperature, as representative of the tissue temperature. Accordingly, improvements are needed to provide feedback during denervation procedures that address these shortcomings of the current technologies.
SUMMARY
[0006] One aspect of the disclosure is directed to a method of performing a therapeutic procedure. The method includes initializing irrigation at or near one or more electrodes on a distal portion of a therapeutic device, applying a therapy to a blood vessel wall via the one or more electrodes, and monitoring an impedance of tissue of the blood vessel. The method also includes transforming the impedance of the tissue of the blood vessel into an estimated temperature of the tissue of the blood vessel; and outputting an indication of the estimated temperature. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.
[0007] Implementations of this aspect of the disclosure may include one or more of the following features. The method further including ending application of therapy in response to determining that a therapy threshold has been exceeded. Determining that the therapy threshold has been exceeded includes determining that the estimated temperature exceeds a maximum estimated temperature threshold. Determining that the therapy threshold has been exceeded further includes determining that a rate of change of the estimated temperature exceeds an estimated temperature rate of change threshold. Determining that the therapy threshold has been exceeded further includes determining that an amount of energy delivered during the therapy exceeds a maximum energy threshold. Determining that the therapy threshold has been exceeded further includes determining that a time for which the therapy has been delivered exceeds a therapy duration threshold. The estimated temperature is determined from the impedance by linear scaling of the impedance. The therapy includes a monopolar radiofrequency therapy, a bipolar radiofrequency therapy, a microwave therapy, or an ultrasound therapy. The method further including displaying a progress of the therapy on a user interface and continuing the therapy. The method further including displaying an indicator of an efficacy of the therapy on a user interface. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium, including software, firmware, hardware, or a combination of them installed on the system that in operation causes or cause the system to perform the actions. One or more computer programs can be configured to perform particular operations or actions by virtue of including instructions that, when executed by data processing apparatus, cause the apparatus to perform the actions.
[0008] A second aspect of the disclosure is directed to a system for denervation of nerves of a blood vessel. The system includes a therapeutic device configured for navigation within a blood vessel of a patient, the therapeutic device including a plurality of electrodes and at least one irrigation channel; an irrigation source in fluid communication with the at least one irrigation channel and configured to irrigate the plurality of electrodes, a therapy source in electrical communication with the plurality of electrodes, and a computing device including a memory and a processor and storing thereon instructions that when executed: initialize irrigation of the plurality of electrodes and the blood vessel, apply a therapy to a blood vessel wall via the plurality of electrodes, monitor an impedance of tissue of the blood vessel, transform the impedance of the tissue of the blood vessel into an estimated temperature of the tissue of the blood vessel, and output an indication of the estimated temperature. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.
[0009] Implementations of this aspect of the disclosure may include one or more of the following features. The system where the computing device stores thereon instructions that determine that a therapy threshold has been exceeded and end application of therapy. The computing device stores thereon instructions that when executed determine that an estimated temperature exceeds a maximum estimated temperature threshold. The computing device stores thereon instructions that when executed determine that a rate of change of the estimated temperature exceeds an estimated temperature rate of change threshold. The computing device stores thereon instructions that when executed determine that an amount of energy delivered during the therapy exceeds a maximum energy threshold. The computing device stores thereon instructions that when executed determine that a time for which the therapy has been delivered exceeds a therapy duration threshold. The computing device stores there on instructions that when executed determine the estimated temperature by linear scaling of the impedance. The therapy source is configured to produce a monopolar radiofrequency therapy, a bipolar radiofrequency therapy, a microwave therapy, or an ultrasound therapy. The computing device stores thereon instructions that when executed display an indicator of progress of the therapy on a user interface. The computing device stores thereon instructions that when executed display an indicator of an efficacy of the therapy on a user interface. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium, including software, firmware, hardware, or a combination of them installed on the system that in operation causes or cause the system to perform the actions. One or more computer programs can be configured to perform particular operations or actions by virtue of including instructions that, when executed by data processing apparatus, cause the apparatus to perform the actions.
[0010] Further disclosed is a system and method of performing a therapeutic procedure, wherein the method includes initializing irrigation at or near one or more electrodes on a distal portion of a therapeutic device, applying a therapy to a blood vessel wall via the one or more electrodes, and monitoring an impedance of tissue of the blood vessel, wherein the method also includes transforming the impedance of the tissue of the blood vessel into an estimated temperature of the tissue of the blood vessel; and outputting an indication of the estimated temperature.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Various aspects and embodiments of the disclosure are described hereinbelow with references to the drawings, wherein:
[0012] FIG. l is a schematic diagram of a therapy system provided in accordance with some examples of the disclosure;
[0013] FIG. 2 is a schematic view of a workstation of the therapy system of FIG. 1;
[0014] 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;
[0015] FIG. 4 is a plot a change in impedance measured by the therapeutic device of FIG.
3 compared to a change in measured temperature of the medium in which the therapeutic device is placed; [0016] FIG. 5 A is a plot of in vivo impedance data measured by the therapeutic device of FIG. 1;
[0017] FIG. 5B is a plot of in vivo temperature data measured by the therapeutic device of FIG. 1;
[0018] FIG. 6 A depicts the impedance data of FIG. 5 A, following a linear function transform, overlaid on the temperature data of FIG. 5B;
[0019] FIG. 6B depicts plot of the rolling average data of FIG. 6 A; and
[0020] FIGs. 7A and 7B depict a method of assessing efficacy of the application of therapy in accordance with some examples of the disclosure.
DETAILED DESCRIPTION
[0021] This disclosure is directed to therapeutic systems and methods and particularly ablation systems and methods. In at least one aspect the disclosure is directed to systems and methods of ablation for denervation or neuromodulation of nerves such as the 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 intra-procedure and post-procedure feedback on the progress of the therapy and intra-procedure safety indicators.
[0022] For ease of description, much of the following description focuses on implementations of RF 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. 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.
[0023] Turning now to the drawings, FIG. 1 illustrates a therapy system provided in accordance with the present disclosure and generally identified by reference numeral 10. As shown in FIG. 1, therapy system 10 may be used in connection with a C-arm imaging system or other imaging station, which may facilitate navigation of a therapeutic device 50 to a desired location within the patient’ s anatomy (e.g. , the patient’ s renal artery), application of denervation therapy to the tissue within the renal artery to denervate sympathetic nerves within the tissue, and monitoring of impedance for use in evaluating the denervation therapy.
[0024] The therapy system 10 includes a workstation 20 and a therapeutic device 50 operably coupled to the workstation 20. The therapy system may be used with an imaging device 70, which may be operably coupled to a display 72. The patient “P” is shown lying on an operating table 12 with the therapeutic device 50 inserted through a portion of the patient’s femoral artery, although it is contemplated that the therapeutic device 50 may be inserted into any suitable portion of the patient’s vascular network that is in fluid communication with a desired blood vessel for therapy. Although generally described as having one therapeutic device 50, it is envisioned that the therapy system 10 may employ any suitable number of therapeutic devices 50. The therapeutic devices 50 may employ the same or different therapy modalities and be operably coupled to the workstation 20. Further, the therapeutic device 50 may employ a guidewire 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 and 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 in a single component and may be referred to as a generator.
[0026] The computer 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, including, but not limited to, power delivery), amongst others. An output module 42 connects the processor 30 and the memory 32 to a variety of output devices such as the display 26. In embodiments, the display 26 may be a touchscreen display.
[0027] The therapy source 24 generates and outputs one or more of RF energy (monopolar or bipolar), microwave energy, ultrasound energy, cryogenic energy, or chemical ablation medium via an automated control algorithm 44 stored on the memory 32 and/or under the control of a clinician. As can be appreciated, many of the therapies listed above change the temperature of the tissue (e.g., increase or decrease the temperature) to achieve the desired denervation of the nerves. The therapy source 24 may be configured to produce a 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 sense voltage and current applied to target tissue via the therapeutic device 50. In addition, one or more sensors on the therapeutic device 50 may monitor the temperature of the target tissue or tissue proximate the target tissue, and/or a portion of the therapeutic device 50. Utilizing the sensed voltage and current applied to the tissue, an application 34 on the computer 22 calculates an impedance of the tissue through which therapeutic energy is transmitted to provide an indication of the status of the tissue. This status, as will be described in greater detail below, may be output to the display 26 on one or more user interfaces 28 to provide a clinician with both intraprocedural and post-procedural feedback regarding the therapy.
[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 at which one or more therapy 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 at the treatment site. Those of skill in the art will recognize in the context used here application of therapeutic energy should be construed to include application of cryogenic cooling to the treatment site to achieve a thermally induced neuromodulation. 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. [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 to the location where the therapy is to be applied, exposing the electrodes 56. The guide wire 50 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 of the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (as shown in FIG. 3). 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 employed without departing from the scope of the disclosure. 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. 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).
[0030] The elongated shaft 52 of the therapeutic device 50 may further include an aperture (not shown) at a distal end thereof and configured to slidably receive a 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). [0031] Still further, the lumen of the guide sheath 58 may optionally be in fluid communication with an irrigation fluid source (e.g., an intravenous fluid bag containing a saline solution). With the elongate shaft 52 advanced from a distal end of the guide sheath 58, irrigation fluid can be permitted to flow through for example, the guide sheath 58 or the elongate shaft 52. The irrigation fluid can flow through a lumen formed in the guide sheath 58 and exits one or more ports (not shown) to flow over all of the electrodes 56. Alternatively, the irrigation fluid flows through a lumen in the elongate shaft 52 and exit ports in or proximal one or more of the electrodes 56. The irrigation fluid passing through the blood vessel can beneficially cool the blood vessel wall limiting damage to the blood vessel wall itself while still allowing desirable heating and therapy to be applied to tissues beyond the blood vessel wall.
[0032] In some examples, each electrode 56 may also incorporate a thermistor or other temperature sensor (not shown) to monitor the temperature of the electrodes 56. As will be appreciated, the electrodes 56 directly contact the inner wall of a blood vessel or other luminal tissues, thus as energy is passed through the electrodes 56, the electrodes 56 themselves begin to heat as heat flows from the affected tissue to the electrodes. The thermistor, thermocouple or other temperature sensor in communication with the electrode 56, generates a signal that is received by the therapy source 24 and provides an indication of the temperature of the electrode 56. As will be appreciated, when no irrigation is employed, the temperature of the electrode will closely approximate the temperature of the tissue adjacent to the electrode 56.
[0033] Continuing with FIG. 3, in embodiments where the therapeutic device 50 is an RF ablation catheter, the energy delivery assembly 54 includes one or more electrodes 56 disposed on an outer surface thereof that are configured to contact a portion of the patient’s vascular tissue when the therapeutic device 50 is placed in the second, expanded configuration. As shown herein, the therapeutic device 50 includes four electrodes 56. However, the present disclosure is not so limited and the therapeutic device 50 may have more or fewer electrodes 56 without departing from the scope of the present disclosure. One of skill in the art will recognize that the electrodes 56 may be replaced with ultrasound transducers, microwave antennae, ports for delivery of cryoablation medium or chemical medium and other implements and/or ablation and denervation modalities without departing from the scope of the present disclosure.
[0034] As illustrated in the figures, the electrodes 56 are disposed in spaced relation to one another along a length of the therapeutic device 50 forming the energy delivery assembly 54. As will be appreciated, these electrodes 56 are in communication with the therapy source 24. In one example the therapy source 24 produces, monopolar RF energy to denervate the sympathetic nerves of the relevant blood vessel. The electrodes 56 may deliver RF energy independently of one another, simultaneously, selectively, or sequentially and in electrical communication with a ground pad (not shown) to enable the application of monopolar RF energy for therapy. Additionally or alternatively, RF energy may be applied between any desired combination of the electrodes 56, without requiring the use of a ground pad (e.g., bipolar).
[0035] Therapy (e.g., RF, microwave, or ultrasound energy) generally causes the temperature of the tissue receiving the therapeutic energy to rise. Similarly, as therapy is applied to the electrodes 56, and there with the tissue receiving the energy (e.g., blood vessel wall) in an effort to denervate the afferent nerves located within and beyond the blood vessel wall the impedance of the tissue through which the energy is passed can be calculated by the therapy source 24 or the computer 22 operably connected thereto. Following Ohm’s law with the voltage and current output of the therapy source 24 known, the impedance of the tissue can be calculated. As will be understood by those of skill in the art, as therapeutic energy is applied to the tissue and the tissue heats, the impedance of the tissue drops.
[0036] FIG. 4 depicts two plots observed during an experimental application of energy to a therapeutic device 50 when placed in a saline bath. The first plot depicts linearly scaled impedance of the tissue observed during the application of therapeutic energy while the second plot depicts the changes in temperature observed as a result of the application of energy. Linearly scaling of the impedance values is achieved with use of the linear equation (1) and temperature and impedance values at two times (ti) and (t2):
(1) T = m*I +c Where:
T= Temperature
I = Impedance m= ratio of change of temperature to change in impedance between a time ti and t2 c= a constant
The linearly scaled impedance value is then calculated using equation (2):
(2) LSI = m*I +c As noted above, two time points are selected (ti) and (t2). These may be specific times during the application of therapy (e.g., at 5s and 20s) or they may be ranges of times (e.g., 5-10s and 15-20s). At each time point (ti) and t2) temperature and impedance values are determined to provide T Ii values and T2, 12 values. Where ranges of times are utilized average temperature and impedance values across that range of time can be calculated. Using equation (1) values for m and c are determined by solving equation (1) for each time (t and t2), thus: at (ti) Ti = m*Ii + c at (t2) T2 = m*I2 + c
Subtracting Equation 1 at (t2) from Equation 1 at (t :
T2 - Ti = m (I2 - I
With all other values known, m can be solved for as: m = (T2 - T1)/(I2 - I1)
Further c can be solved for from Equation 1 at either (ti) or (t2), for example: c = T2 - m*I2
[0037] Once m and c are resolved, the Linearly scaled impedance (LSI) can be calculated using Equation (2) at any time for which there is impedance data. As can be seen in FIG. 4, temperature and the linearly scaled impedance correlate nearly perfectly (i.e., rises in linearly scaled impedance are highly correlated with rises in temperature). In the context of the experiment, as the temperature of the saline increases, its conductivity increases. Thus, the increase in temperature is associated with a decrease in resistance or impedance. In FIG. 4 therapeutic energy (e.g., ablation or denervation energy) is initially applied at the 10 second mark and ceased at the 70 second mark.
[0038] As will be appreciated, the experimental results depicted in FIG. 4 demonstrate that there is a relationship between temperature and impedance. However, this is a demonstration of a substantially “perfect” experiment. It is a perfect experiment in the sense that each of the electrodes 56 of the therapeutic device 50 is completely submerged in the saline. As a result of the complete submergence of the electrodes 56, 100% of electrode surface area is exposed to and in contact with the saline. Thus, throughout the course of the experiment, the impedance of the saline was only a function of its temperature. This was in part achieved by minimizing any change in salinity of the saline by limiting the evaporation. The experiment, as shown by the plots in FIG. 4, demonstrates the primary relationship between impedance and temperature. [0039] Those of ordinary skill in the art will recognize that, when treating a patient, the blood vessels (e.g., the renal arteries) do not present a uniform medium for application of energy and measuring the effects of that application. When applying therapy to blood vessels, the impedance of the tissue is no longer purely a function of temperature. In addition to temperature, impedance is a function of degree of contact of the electrodes 56 to blood vessel wall. Blood in the blood vessel is generally more conductive than the tissue of the blood vessel wall, thus as the degrees of electrode 56 surface area contacting with the blood vessel wall changes, the impedance will vary. A variety of factors can affect the surface area of the electrode 56 contacting the blood vessel wall, one such factor is the heartbeat of the patient, causing the diameter of the blood vessel to vary in diameter as the volume of blood forced through the blood vessel increases and decreases though the cardiac cycle. Another cause for change in impendence experienced in-vivo when applying therapy is the permanent and irreversible tissue damage caused by the application of therapeutic energy. In large part, this permanent tissue damage is the dehydration of the cells of the blood vessel wall and other tissues of the blood vessel (including the nerves being targeted for denervation. The dehydration of these tissues permanently changes the tissue impedance even when the temperature of the tissue returns to baseline.
[0040] Further, as noted above, the detected temperature of the electrode is effectively lost when employing an irrigating fluid at the treatment site by the cooling of the electrodes. To provide an accurate and useful feedback mechanism for clinicians and or the generator to utilize during procedures, these more complicated relationships need to be taken into account.
[0041] FIG. 5A depicts impedance data acquired from in vivo application of therapeutic energy to a blood vessel wall of a patient. As with FIG. 4 the therapeutic energy is applied via the electrodes 56 starting at the 10 second mark of the plot and terminates at about the 70 second mark. The depicted oscillations in the data of the plot are associated with the heartbeat of the patient and reflect changes in the degree of contact of the electrodes 56 with the blood vessel wall. FIG. 5B depicts a plot of the temperature during the same period of application of therapeutic energy to the blood vessel of the patient. Like with the impedance data plotted in FIG. 5A, oscillations are also seen in the plotted in-vivo temperature data. However, unlike the plotted impedance data, the oscillations only begin after application of the therapeutic energy (e.g., ablation) begins. Once the application of the therapeutic energy begins (at the 10 second mark in the plot) a temperature gradient is established between the blood vessel wall and the blood flowing through blood vessel. During the application of therapeutic energy, the blood vessel wall is warmer than blood flowing through the blood vessel. Further, the pulsatile flow of body temperature blood through the blood vessel (e.g., the renal artery) and varying degree of electrode 56 contact with the tissue of the blood vessel wall causes a thermal convection capacity of the blood to vary with time resulting in the observed oscillations in the plot. Despite the oscillations observed in the plots of FIGS. 5A and 5B, a correlation or relationship between the impedance data and the temperature data can be observed.
[0042] FIG. 6 A depicts the impedance data of FIG. 5 A after application of a linear function transform plotted over the temperature data of FIG. 5B. FIG. 6B depicts the same data as FIG. 6A when transformed into rolling average values during the application of therapeutic energy via the electrodes 56 to the blood vessel wall. In FIG. 6B by averaging the data the oscillations are smoothed by reducing the impact of changes in electrode 56 contact with the blood vessel wall caused by the patient’s heartbeat and changes in blood vessel diameter.
[0043] As can be seen in FIG. 6B from the start of the application of therapeutic energy at about the 10 second mark of the plot to about the 25 second mark of the plot, the temperature data and the linearly scaled impedance data strongly correlate, and as shown in the plot overlap. For the rest of the plot in FIG. 6B, the linearly scaled impedance data and the temperature data separate, in part due to the onset of the permanent tissue damage, described above. This separation results in a tracking error between the temperature data and the impedance data from about the 25 second mark until the cessation of application of therapeutic energy to the blood vessel wall. As the application of therapeutic energy continues the tracking error between the temperature data and the impedance data increases. This increase in tracking error is a component of the decrease in impedance (see FIG. 5A impedance without linear scaling) associated with the increasing permanent tissue change (e.g., damage) as the application of therapeutic energy continues. The larger the tracking error, the greater the degree of tissue damage that is achieved by the application of therapeutic energy.
[0044] Because the impedance data, and more particularly the linearly scaled impedance data, generally tracks (albeit with an increasing error over time) the temperature data, the linearly scaled impedance data provides an estimated temperature of the tissue through which the current from the therapy source 24 passes (e.g., between electrodes 56 and a ground pad or between electrodes 56). This estimated temperature can be utilized in one or more applications 34 running on computer 22 for control of the therapy source 24 to achieve a desired therapeutic outcome while limiting undesirable damage to other tissues (e.g., the blood vessel wall) as outlined in greater detail below.
[0045] As an initial matter, the use of the linearly scaled impedance data provides an estimated temperature for irrigated therapeutic devices 50. As noted above, where irrigation is employed the temperature data that might be received from a thermistor or other sensor associated with the electrodes 56 is lost due to the differences in temperature of the irrigation medium. Thus, use of an estimated temperature based on the linearly scaled impedance data (which is not affected by the irrigation medium) provides useful temperature data for irrigated therapeutic devices 50, without requiring additional hardware or components on the therapeutic device 50, and indeed, the temperature sensing elements may in fact be eliminated from the therapeutic device 50. However, the utility of the estimated temperature based on the linearly scaled impedance data is not limited to irrigated therapeutic devices 50 and may be employed on non-irrigated therapeutic device 50.
[0046] In accordance with one aspect of the disclosure, the linearly scaled impedance data (i.e., the estimated temperature) can be used directly by the applications 34 as the actual temperature data without any accounting for the tracking error. Because, as depicted in FIG. 6B the linearly scaled impedance provides an estimate of the temperature which exceeds the temperature when measured by a thermistor or other temperature sensor in connection with the electrodes 56, this estimate does not present any safety issues and is thus a conservative estimate of the temperature of the tissue through which the current is passing.
[0047] In accordance with other examples of the disclosure, a correction factor may be determined based on empirical data to correct for the divergence between the linearly scaled impedance and the temperature. For instance, over the course of a series of cases where therapy is applied to blood vessels, a correction factor can be calculated based on a comparison of the measured temperature (without irrigation) at the electrodes 56 and the estimated temperature (i.e., the linearly scaled impedance data). The correction factor is a value which adjusts or minimizes the tracking error between the two values during the application of the therapy. . In one case, the correction factor could be an average difference between a measured temperature and an estimated temperature of a number of patients. As will be appreciated, the difference between the measured and the estimated temperatures changes over time during the application of therapy, thus the correction factor may include a time-based variable. Alternatively, where therapy duration is fixed, the correction factor may be based on the difference of the measured and estimated temperatures at the conclusion of the therapy. Once determined, for all future patients, the correction factor is applied to the estimated temperature (i.e., linearly scaled impedance data) to reduce the value of the estimated temperature to a temperature believed to more closely match the actual temperature.
[0048] Alternatively, the correction factor may be more sophisticated and vary from patient to patient or group to group. In one example, a rate of change of temperature over a specified period (e.g., the first 10 seconds following commencement of the therapy) may provide a basis to predict the changes in impedance during the subsequent portion of the application of therapy and therewith define a correction factor. Similarly, an initial impedance may be measured either with a non-therapeutic pulse of energy immediately prior to the onset of therapy or a therapeutic energy pulse immediately with the onset of the application of therapy. The impedance from an initial measurement, before the tissue has received sufficient energy to heat the tissue, and particularly to the point where typically the tracking error (FIG. 6B) can be initially observed, provides an individualized baseline value for comparison. Once established this baseline temperature can be used for the rate of change determination (described above) or for a magnitude of change determination. A rate of change or a magnitude of change which results in termination of the application of therapy may be individually based on factors of the patient such as age, body-mass index, relative fitness, and others. Thus, a measured change in impedance magnitude, or a rate of change of impedance or a combination of the two may be used for patient specific safety stop for the application of therapy or an endpoint determination of the therapy. Further, one or both of these may be incorporated into a visual indicator that may be displayed in the user interface 28 on the display 26 to provide indicators on the estimated temperature of the tissue beyond the blood vessel wall or a progress indicator on the user interface 28.
[0049] As noted above, the use of the impedance data is particularly useful in the context of the irrigated catheter. Initially, sensor-based temperature data is generally not useful with irrigated catheters. Irrigation allows the use of higher power (e.g., greater energy) applications of therapy. The higher power applications of therapy allow for deeper (as measured from the interior surface of the blood vessel wall) penetration of the therapy to the tissues, including the nerves (e.g., sympathetic nerves) to achieve more complete denervation. Finally, the impedance data, as described above, can be utilized to generate an estimated temperature of the tissue beyond the blood vessel wall and allow for thermal observation of the progress of the therapy as reported to a user via a user interface 28 on display 26.
[0050] Though generally described in connection denervation as described herein above, the disclosure is not so limited. The use of linearly scaled impedance to estimate temperature or as a proxy for temperature can be implemented in other aspects including without limitation stimulation or other neuromodulation of nerves in or around the blood vessel or other luminal tissues.
[0051] FIGs. 7A and 7B depict a flow chart showing a method 700 in accordance with the disclosure. At step 702, the therapeutic device 50 is placed at a desired location within the patient (e.g., in a renal or hepatic artery). As part of the placement, the therapeutic device 50 may be advanced from the catheter 58 and the therapeutic device 50 allowed to expand such that the electrodes 56 are in contact with an inner wall of the blood vessel.
[0052] At step 704 irrigation is initiated. Though described as occurring prior to initialization of therapy (Step 708), irrigation may be initialized at any point during the method 700 between steps 702 and step 722. This may be as simple as permitting flow from an intravenous-type bag through the therapeutic device or may include the starting a pump such as a peristaltic pump to pump fluid from a fluid source through the therapeutic device. At step 706 an initial impedance is detected, this may be achieved by application of a pulse of either therapeutic or non-therapeutic energy, if therapeutic energy is being used to detect the initial impedance, step 706 may be part of (e.g., first two seconds) of step 708 where therapy is initialized. Once therapy is initialized, the impedance of the tissue to which therapy is being applied is monitored at step 710. The impedance data is transformed at step 712 to an estimated temperature (e.g., via linear scaling) as depicted for example in FIG. 6B. While the therapy is being applied one or more optional steps 714, 722, 724, or 726 may be undertaken to determine when or whether to terminate the application of the therapy. In step 714 a determination is made whether the estimated temperature from step 712 exceeds a maximum threshold. If the answer is yes, the method proceeds to step 716 where the therapy application and irrigation are ended. If the answer is no, the method progresses to step 718 where are progress of the therapy is displayed on a user interface 28, as described above. The method then progresses to step 720 where the therapy is continued and then back to step 710 where the impedance is monitored.
[0053] Additionally or alternatively, following a no at step 714 or immediately following step 712 the method progresses to step 722 where a determination is made whether a rate of change of the estimated temperature from step 712 exceeds a threshold, again if yes, the method moves to step 716 where irrigation and therapy application are stopped and if no the method moves to step 718, described above. Again, additionally or alternatively, following a no at step 714 and/or step 722 or immediately following step 712 the method progresses to step 724 where a determination is made whether a maximum amount of energy has been applied to the tissue. As with steps 714 and 722, a yes at step 724 results in the method moving to step 716 where irrigation and therapy application are stopped and if no the method moves to step 718, described above. A further optional step may follow a no at step 724 where a determination is made whether the therapy has timed out at step 726. Again, a no at step 726 leads to step 718 for display of the progress on the user interface 28 and a yes results in ending of the therapy and irrigation at step 716.
[0054] As described herein, at step 718 of method 700 an indicator of the progress of the therapy may be displayed on the UI 28 and similarly a display of the efficacy of the therapy may be displayed at step 728. These indicators may be as simple as a color-coded display where a red indicator signals an inefficacious or incomplete therapy, and a green indicator signals an efficacious therapy. Additionally or alternatively, the indicator may be more granular, and based on the monitored impedance, a percentage of completeness of the therapy may be displayed. This may be coupled with more colors, where red is 0-50% complete, orange is 50- 75% complete, yellow is 75-95% complete, and green is greater than 95% complete. Alternatively, the UI 28 may display a rolling indicator of the temperature value from step 712. In this way, the clinician may observe the changes in impedance during the procedure and assess whether to terminate method 700 on their own during the procedure (e.g., without the determinations of steps 714, 722, 724, or 726). Other indicators may include written words on the UI 28, audible sounds to indicate efficacy or progress of the therapy, and combinations of each of these without departing from the scope of the disclosure. The clinician may, based on the displayed efficacy indicated at step 728, determine to reinitiate therapy at the current location at step 730, and the method returns to step 710.
[0055] The therapeutic devices 50 contemplated in this disclosure can apply one or more of a variety of therapeutic modalities. For example, the therapeutic modalities considered within the scope of this disclosure include monopolar or bipolar radiofrequency, microwave, ultrasound, , and other yet to be developed modalities. Any of these therapy modalities may be incorporated into a therapeutic device 50, which is configured for navigation to a desired location within the patient. The therapeutic device 50 is configured to deliver one or more of these therapeutic modalities may be percutaneously navigated, for example via the femoral artery, to reach the blood vessels of the aorta including the renal arteries, celiac artery, hepatic arteries, splanchnic arteries, mesenteric arteries, and others that are enervated with sympathetic nerves or are proximate one or more sympathetic nerve ganglia. Such a catheter may also be laparoscopically placed in one or more of the above-identified blood vessels, or another luminal tissue without departing from the scope of the present disclosure.
[0056] In accordance with aspects of the present disclosure, the therapeutic device may be navigated within the vessels or luminal tissue in one configuration (e.g., a linear configuration) and once located at a desired location, deployed or otherwise actuated to achieve a second configuration.
[0057] 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.
[0058] 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).
[0059] 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.
[0060] EXAMPLES
[0061] The disclosure is further described in connection with the following examples in which:
[0062] Example 1 : A method of performing a therapeutic procedure, comprising: initializing irrigation at or near one or more electrodes on a distal portion of a therapeutic device ; applying a therapy to a blood vessel wall via the one or more electrodes; monitoring an impedance of tissue of the blood vessel; transforming the impedance of the tissue of the blood vessel into an estimated temperature of the tissue of the blood vessel; and outputting an indication of the estimated temperature.
[0063] Example 2: The method of example 1, further comprising ending application of therapy in response to determining that a therapy threshold has been exceeded.
[0064] Example 3: The method of example 2, wherein determining that the therapy threshold has been exceeded comprises determining that the estimated temperature exceeds a maximum estimated temperature threshold.
[0065] Example 4: The method of example 2 or 3, wherein determining that the therapy threshold has been exceeded further comprises determining that a rate of change of the estimated temperature exceeds an estimated temperature rate of change threshold.
[0066] Example 5 : The method of any one of examples 2 to 4, wherein determining that the therapy threshold has been exceeded further comprises determining that an amount of energy delivered during the therapy exceeds a maximum energy threshold.
[0067] Example 6: The method of any one of examples 2 to 5, wherein determining that the therapy threshold has been exceeded further comprises determining that a time for which the therapy has been delivered exceeds a therapy duration threshold. [0068] Example 7: The method of any one of examples 1 to 6, wherein the estimated temperature is determined from the impedance by linear scaling of the impedance.
[0069] Example 8: The method of any one of examples 1 to 7, wherein the therapy comprises a monopolar radiofrequency therapy, a bipolar radiofrequency therapy, a microwave therapy, or an ultrasound therapy.
[0070] Example 9: The method of any one of examples 1 to 8, further comprising displaying a progress of the therapy on a user interface and continuing the therapy.
[0071] Example 10: The method of any one examples 1 to 9, further comprising displaying an indicator of an efficacy of the therapy on a user interface.
[0072] Example 11 : A system for denervation of nerves of a blood vessel comprising: a therapeutic device configured for navigation within a blood vessel of a patient, the therapeutic device comprising a plurality of electrodes and at least one irrigation channel; an irrigation source in fluid communication with the at least one irrigation channel and configured to irrigate the plurality of electrodes; a therapy source in electrical communication with the plurality of electrodes; and a computing device including a memory and a processor and storing thereon instructions that when executed: initialize irrigation of the plurality of electrodes and the blood vessel; apply a therapy to a blood vessel wall via the plurality of electrodes; monitor an impedance of tissue of the blood vessel; transform the impedance of the tissue of the blood vessel into an estimated temperature of the tissue of the blood vessel; and output an indication of the estimated temperature.
[0073] Example 12: The system of example 11, wherein the computing device stores thereon instructions that determine that a therapy threshold has been exceeded and end application of therapy.
[0074] Example 13: The system of example 12, wherein the computing device stores thereon instructions that when executed determine that an estimated temperature exceeds a maximum estimated temperature threshold. [0075] Example 14: The system of examples 12 or 13, wherein the computing device stores thereon instructions that when executed determines that a rate of change of the estimated temperature exceeds an estimated temperature rate of change threshold.
[0076] Example 15: The system of any one of examples 12 to 14, wherein the computing device stores thereon instructions that when executed determines that an amount of energy delivered during the therapy exceeds a maximum energy threshold.
[0077] Example 16: The system of any one of examples 12 to 15, wherein the computing device stores thereon instructions that when executed determine that a time for which the therapy has been delivered exceeds a therapy duration threshold.
[0078] Example 17: The system of any one of examples 12 to 16, wherein the computing device stores there on instructions that when executed determine the estimated temperature by linear scaling of the impedance.
[0079] Example 18: The system of any one of examples 11 to 17, wherein the therapy source is configured to produce a monopolar radiofrequency therapy, a bipolar radiofrequency therapy, a microwave therapy, or an ultrasound therapy.
[0080] Example 19: The system of any one of examples 11 to 18, wherein the computing device stores thereon instructions that when executed display an indicator of a progress of the therapy on a user interface.
[0081] Example 20: The system of any one of examples 11 to 19, wherein the computing device stress thereon instructions that when executed display an indicator of an efficacy of the therapy on a user interface.
[0082] 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.