EP4051147A1

EP4051147A1 - Modulating renal denervation energy delivery

Info

Publication number: EP4051147A1
Application number: EP20811201.1A
Authority: EP
Inventors: Paul Coates
Original assignee: Medtronic Ardian Luxembourg SARL
Current assignee: Medtronic Ireland Manufacturing ULC
Priority date: 2019-10-31
Filing date: 2020-10-28
Publication date: 2022-09-07
Also published as: CN114901181A; WO2021086984A1

Abstract

Methods, systems, devices, assemblies and apparatuses for renal denervation. The therapeutic assembly includes a first energy delivery element configured to deliver energy to a treatment site. The therapeutic assembly includes a first sensor coupled to the first energy delivery element. The first sensor is configured to measure a first temperature of the first energy delivery element. The therapeutic assembly includes a processor coupled to the first sensor and the first energy delivery element. The processor is configured to increase the delivery of energy to the treatment site when the first temperature is less than or equal to a first threshold temperature, and adjust the delivery of energy to the treatment site when the first temperature is greater than or equal to a second threshold temperature.

Description

MODULATING RENAL DENERVATION ENERGY DELIVERY

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Patent

Application No. 62/928,844 titled “MODULATING RENAL DENERVATION ENERGY

DELIVERY,” filed on October 31, 2019, and the entirety of which is hereby incorporated by reference herein.

BACKGROUND

[0002] 1. Field

[0003] This specification relates to a system, a device, a method and/or an apparatus for modulating energy delivery during renal denervation.

[0004] 2. Description of the Related Art

[0005] Renal denervation is a minimally invasive procedure to treat resistant hypertension.

During renal denervation, a nurse, doctor, technician or other hospital staff (or “clinician”) uses stimuli or energy, such as radiofrequency, ultrasound, cooling or other energy, to perform ablation within the renal arteries. This reduces activity of the nerves surrounding the vessel, which has been shown to result in a decrease in blood pressure and other benefits. The clinician uses the renal denervation device to deliver the stimuli or energy to the treatment site, e.g., through one or more electrodes of the renal denervation device. The renal denervation device may deliver radiofrequency (RF) energy through the electrode to the treatment site, which heats the wall of the vessel, and as a consequence, warms the electrode in contact with the wall of the vessel. This is because the heat from the treatment site may pass to the electrode from the wall of the blood vessel.

Overheating of the wall of the blood vessel may cause thermal damage to the wall of the blood vessel, which may lead to stenosis and may cause vessel constriction and hypertension. Additionally, overheating of an overly large zone may cause damage to adjacent tissues, such as the kidney, small intestine, psoas muscle, ureter and/or other tissue. Thus, the temperature must be monitored and managed to prevent thermal damage to the tissues.

[0006] Accordingly, there is a need for a system, apparatus and/or method to manage, adjust or otherwise control the temperature to prevent thermal damage.

SUMMARY

[0007] In general, one aspect of the subject matter described in this specification is embodied in a therapeutic assembly for renal denervation. The therapeutic assembly includes a first energy delivery element configured to deliver energy to a treatment site. The therapeutic assembly includes a first sensor coupled to the first energy delivery element. The first sensor is configured to measure a first temperature of the first energy delivery element. The therapeutic assembly includes a processor coupled to the first sensor and the first energy delivery element. The processor is configured to increase the delivery of energy to the treatment site when the first temperature is less than or equal to a first threshold temperature, and adjust the delivery of energy to the treatment site when the first temperature is greater than or equal to a second threshold temperature.

[0008] These and other embodiments may optionally include one or more of the following features. The processor may be configured to adjust the delivery of energy to the treatment site from a first amount of energy to a second amount of energy. The first amount of energy may be different than the second amount of energy. The processor may be configured to provide, using the first energy delivery element, the first amount of energy to the treatment site prior to adjusting the delivery of energy to the treatment site. The processor may be configured to provide, using the first energy delivery element, the second amount of energy to the treatment site after adjusting the delivery of energy to the treatment site. The processor may be configured to turn off, disable or otherwise power off the first energy delivery element to adjust the delivery of energy to the treatment site when the first temperature is greater than or equal to the second threshold temperature.

[0009] The therapeutic assembly may include a second energy delivery element. The second energy delivery element may be configured to deliver a second amount of energy to a second location of the treatment site. The first energy delivery element may be configured to deliver a first amount of energy to a first location of the treatment site. The therapeutic assembly may decrease the first amount of energy delivered by the first energy delivery element and decrease the second amount of energy delivered by the second energy delivery element to the second location of the treatment site.

[0010] The therapeutic assembly may include a catheter coupled to the first sensor and the first energy delivery element. The catheter may be configured to be intravascularly inserted into the vessel. The vessel may be a renal artery. The first sensor may be coupled to the first energy delivery element. The therapeutic assembly may include a radio frequency generator. The radio frequency generator may be configured to deliver the energy to the first energy delivery element.

The energy may be a radiofrequency signal. The first energy delivery element may be an electrode.

[0011] In another aspect, the subject matter is embodied in a therapeutic assembly for renal denervation. The therapeutic assembly includes a first electrode configured to deliver energy to a treatment site. The therapeutic assembly includes a first temperature sensor coupled to the first electrode and configured to measure a first temperature of the first electrode. The therapeutic assembly includes a processor coupled to the first temperature sensor and the first electrode. The processor is configured to increase the delivery of energy to the treatment site when the first temperature is less than or equal to a first threshold temperature and decrease the delivery of energy to the treatment site when the first temperature is greater than or equal to a second threshold temperature.

[0012] In another aspect, the subject matter is embodied in a method for modulating energy delivered during renal denervation. The method includes determining, by a processor and using a sensor, a temperature of an electrode at a treatment site during a first time period. The method includes determining, by the processor, that the temperature of the electrode is greater than or equal to a threshold temperature during the first time period. The method includes decreasing, by the processor, an amount of energy delivered to the treatment site when the temperature of the electrode is greater than or equal to the threshold temperature.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Other systems, methods, features, and advantages of the present invention will be or will become apparent to one of ordinary skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the present invention, and be protected by the accompanying claims. Component parts shown in the drawings are not necessarily to scale and may be exaggerated to better illustrate the important features of the present invention. In the drawings, like reference numerals designate like parts throughout the different views.

[0014] FIG. 1 shows an example conceptual illustration of the therapeutic assembly according to an aspect of the invention.

[0015] FIG. 2A shows an example renal denervation device of the therapeutic assembly of

FIG. 1 in a low-profile delivery configuration according to an aspect of the invention. [0016] FIG. 2B shows an example renal denervation device of the therapeutic assembly of

FIG. 1 in an expanded deployed configuration according to an aspect of the invention.

[0017] FIG. 3 shows an example renal denervation device of the therapeutic assembly of FIG.

1 in the expanded deployed configuration within a blood vessel according to an aspect of the invention.

[0018] FIG. 4 is a block diagram of an example generator of the therapeutic assembly of FIG.

1 according to an aspect of the invention.

[0019] FIG. 5 is a flow diagram of an example process for controlling the energy delivered to the one or more energy delivery elements of the therapeutic assembly of FIG. 1 according to an aspect of the invention.

[0020] FIG. 6 is a flow diagram of an example process for regulating the energy delivered using the therapeutic assembly of FIG. 1 according to an aspect of the invention.

[0021] FIG. 7 is a graphical illustration of measured temperatures of the energy delivery elements of the therapeutic assembly of FIG. 1 according to an aspect of the invention.

DETAILED DESCRIPTION

[0022] Disclosed herein are systems, devices, methods and/or apparatuses for a therapeutic assembly including a renal denervation device that controls an amount of energy delivered by each energy delivery element, such as an electrode, to manage the temperature at the treatment site.

Generally, a renal denervation device delivers a constant amount of energy to the one or more energy delivery elements, but due to the changes in blood flow, the temperature at the treatment site will oscillate between a minimum and maximum temperature. This may cause the renal denervation device to inadvertently cause damage to the wall of the blood vessel when the temperature becomes too high and/or not effectively innervate the nerves when the temperature becomes too low. However, a renal denervation device that modulates the delivery of the energy to the treatment site based on the temperature can minimize temperature oscillations to effectively provide treatment to the nerves while preventing damage to the wall of the blood vessel, such as to the intima and/or endothelium layers within the vessel wall, or other tissue surrounding the renal artery such as the kidney or ureter.

[0023] The energy modulating renal denervation device (“renal denervation device”) has one or more integrated sensors that measure the temperature of the energy delivery element positioned on the wall of the vessel and/or the temperature at the treatment site at a location on the wall of the vessel, such as the renal artery. For example, the renal denervation device may monitor different aspects of the temperature including an average temperature, a minimum and/or a maximum temperature and the frequency of the cycles of the temperature between the minimum and/or the maximum temperature. When the temperature is greater than or equal to a threshold amount, which may indicate that damage to the wall of the vessel or other tissue is occurring, and/or when the temperature is less than or equal to a second threshold amount, which may indicate that the renal denervation device is not effectively innervating the nerves, the renal denervation device modulates or controls the amount of energy delivered through the energy delivery element to the wall of the vessel. This minimizes the oscillation and/or variability in the temperature, but does not eliminate the oscillation and/or variability entirely. Some oscillation may need to remain so that the renal denervation device is able to detect or determine the heartbeat to use as a trigger to control, manage or otherwise modulate the amount of energy delivered through the energy delivery element.

[0024] In some implementations, the heartbeat may be determined using an additional device that supplies energy or power at a constant rate to cause a measurable increase in the temperature so that the heart rate may be determined based on the oscillation of the temperature. The additional device may have a sensor that measures the temperature. The power, energy or temperature increase would be selected low enough so as to not cause any change to any tissue with which the additional device contacts and may be designed to ensure that the additional device does not contact the vessel wall.

[0025] Other benefits and advantages include controlling each energy delivery element independently. The renal denervation device may have multiple energy delivery elements that are positioned at different locations within or along the wall of the vessel. The renal denervation device may control the delivery of energy through each of the one or more energy delivery elements independently to manage the temperature of tissue at the treatment site.

[0026] Additionally, the renal denervation device may measure and control the amount of energy delivered in real-time to mitigate temperature oscillations due to changes in blood flow.

For example, the temperature at the treatment site and/or the electrode will vary during systole and diastole due to the difference in blood flow. The temperature drops during systole because a wave of cooling blood is pushed down the renal artery and rises during diastole because the blood flow slows. Thus, the renal denervation device may increase energy delivery during systole and decrease energy delivery during diastole to reduce the temperature oscillation. In particular, modulation of the energy reduces temperature peaks that occur as a result of changes in blood flow when the heart beats, which minimizes damage to the blood vessel while ensuring sufficient temperature to modulate the nerves per the requirements of the renal denervation device.

[0027] FIG. 1 shows the therapeutic assembly 100. The therapeutic assembly 100 performs renal denervation within the renal artery of a human patient. Renal denervation is a minimally invasive procedure to treat resistant hypertension. The therapeutic assembly 100 includes a renal denervation device 102 and/or a generator 104. The renal denervation device 102 may include any device that delivers energy or stimulus to a target nerve within a wall of a blood vessel, such as the renal nerve of the renal artery. The energy or stimulus may include, for example, at least one of a radio frequency stimulus, a thermal stimulus, a cryogenic stimulus, a microwave stimulus, an ultrasonic stimulus or other form of energy or stimulus. Regardless of the type of energy delivered, the renal denervation device 102 does not fully occlude the blood vessel, and thus, blood may continue to flow through the blood vessel.

[0028] The renal denervation device 102 has a catheter 108, one or more energy delivery elements 110, such as an electrode, and/or one or more sensors 112, such as a temperature sensor.

The renal denervation device 102 may have an elongated shaft 114 with a handle 116. The elongated shaft 114 with the handle 116 may be used to guide and/or advance a distal portion of the catheter 108 through the blood vessels of the patient, such as a human patient, to a target location of a blood vessel and remotely manipulate the distal portion of the catheter 108. The catheter 108 may be intravascularly delivered into the patient, e.g., a blood vessel of the patient, in a low-profile configuration, such as the substantially straight configuration shown in FIG. 1.

The catheter 108 may be over a meter in length. Upon delivery to a target location within and along the blood vessel, the catheter 108 may be deployed into an expanded deployed configuration, such as a generally helical or spiral configuration or other suitable configuration, which the one or more energy delivery elements 110, such as one or more electrodes, may contact the blood vessel, as shown in FIG. 3 for example. In the expanded deployed state, the renal denervation device 102 may deliver energy at a treatment site and provide therapeutically-effective electrically and/or thermally induced denervation to a nerve within the wall of the blood vessel. FIGS. 2A-2B show the deployment of the renal denervation device 102. In particular, FIG. 2A shows the catheter 108 in the low-profile configuration, and FIG. 2B shows the catheter 108 in the expanded deployed configuration.

[0029] The catheter 108 may have a distal tip 202. The distal tip 202 points into the lumen of the blood vessel. The distal tip 202 may have a high density marker band 204. The high density marker band 204 allows a clinician to identify the distal tip 202 of the catheter 108 under fluoroscopy. The distal portion of the catheter 108 may be approximately 4 cm - 5 cm in length, and the distal tip 202 may be approximately 1 cm - 2 cm in length.

[0030] The catheter 108 may have a wire 206 within the lumen of the catheter 108. The distal tip 202 allows the wire 206 to extend out and away from the distal tip 202 when the catheter 108 is in the low-profile configuration and to be advanced through the blood vessels to the target location of the blood vessel. When the wire 206 is retracted within the distal tip 202 and into the catheter 108, the catheter 108 changes shape from the low-profile configuration, such as the substantially straight configuration, as shown in FIG. 2A for example, to the expanded deployed configuration, such as a generally helical or spiral configuration, as shown in FIG. 2B for example.

[0031] The renal denervation device 102 has one or more energy delivery elements 110. The one or more energy delivery elements 110 may include an electrode, such as a radiofrequency electrode, a radiofrequency probe, a thermal probe, a cryogenic probe, a microwave probe, an ultrasonic probe, an optical source or a chemical injector. The one or more energy delivery elements 110 may deliver and/or provide neuromodulation energy, such as radiofrequency energy, thermal energy, microwave energy, ultrasound energy or other neuromodulation energy, to ablate nerves at or around a treatment site located on a wall of the blood vessel. The one or more energy delivery elements 110 may be positioned on the distal portion of the catheter 108. The one or more energy delivery elements 110 may include multiple energy delivery elements 110, such as the energy delivery elements 110a-d, as shown in FIGS. 2A, 2B and 3 for example. The energy delivery elements 110a-d may be arranged approximately 90 degrees apart relative to a longitudinal axis that runs through the center of the catheter 108 when in the spiral configuration.

The energy delivery elements 110 may be spaced any suitable distance from each other, and the spacing may vary based on the application of the therapeutic assembly 100 and its intended use.

[0032] When there are multiple energy delivery elements 110, each energy delivery element

110 may deliver power independently, either simultaneously, selectively, and/or sequentially, to a treatment site. The multiple energy delivery elements 110 may deliver power among any desired combination of the one or more energy delivery elements 110. The multiple energy delivery elements 110 may include any number of energy delivery elements 110.

[0033] The one or more energy delivery elements 110 may be introduced into and advanced along a blood vessel 304, such as the renal artery and may be positioned to contact the blood vessel

304 in the expanded deployed configuration at different intervals and/or locations along the wall of the blood vessel 304. For example, a first energy delivery element 110a may contact the wall of the blood vessel 304 at a first location 302a, a second energy delivery element 110b may contact the wall of the blood vessel 304 at a second location 302b, a third energy delivery element 110c may contact the wall of the blood vessel 304 at a third location 302c and a fourth energy delivery element 110d may contact the wall of the blood vessel 304 at a fourth location 302d. The renal denervation device 102 may deliver energy through the one or more energy delivery elements 110 at the treatment site and provide therapeutically-effective electrically- and/or thermally- induced denervation.

[0034] The renal denervation device 102 includes one or more sensors 112. The one or more sensors 112 may be a temperature sensor that measures the temperature at a location of the wall of the blood vessel. The temperature may be the temperature of the one or more energy delivery elements 110 at the location of the wall of the blood vessel and/or the temperature at the treatment site. The temperature may be used to interpolate the heart rate of the patient. Each of the one or more sensors 112 may be coupled to, integrated with or in a close proximity to a corresponding one of the one or more energy delivery elements 110. This allows each of the one or more sensors

112 to measure the local temperature of the heating of the localized tissue. For example, the first sensor 112a may be integrated with the first energy delivery element 110a, the second sensor 112b may be integrated with second energy delivery element 110b, the third sensor 112c may be integrated with the third energy delivery element 110c and the fourth sensor 112d may be integrated with the fourth energy delivery element 110d, as shown in FIG. 2B for example.

[0035] The one or more sensors 112 may be another type of sensor that measures a different parameter, such as impedance, pressure, optical, flow, or amount of chemical. The one or more sensors 112 may be proximate to or within the energy delivery element 110. For example, the energy delivery element 110 may be an electrode, which has two wires. One wire may be made from copper and the other may be made from a copper-nickel allow. The wires may both transmit the signal from the sensor 112 and also convey the energy to the energy delivery element. The signal may be a temperature signal that indicates the temperature of the blood vessel.

[0036] The two wires may measure the temperature through a thermocouple effect. The two wires may have a voltage gap, and as the temperature changes due, to the change in blood flow at the treatment site, the amount of voltage across the voltage gap changes. For example, when there is more blood flowing at the treatment site, there is a cooling effect, which results in a decrease in temperature, and when there is less blood flowing at the treatment site, there is a warming effect, which results in an increase in temperature. The amount of voltage across the voltage gap may be measured and may be associated to a temperature at the treatment site.

[0037] The therapeutic assembly includes a generator 104. The generator 104 may be a radio frequency generator or other generator that delivers a denervation stimulus or energy through the one or more energy delivery elements 110 to the wall of the blood vessel at the treatment location.

The denervation stimulus may include a non-electric stimulus, for example, a chemical agent, optical stimulus, a thermal stimulus, a cooling stimulus, a microwave stimulus or other form of stimuli. The generator 104 may have a cable, an electrical lead and/or wire that is electrically conductive and runs through the catheter 108 within a lumen and is electrically coupled with the one or more energy delivery elements 110. In some implementations, the generator 104 may have separate leads and/or wires that electrically couple with a corresponding energy delivery element

110 of the one or more energy delivery elements 110 so that each energy delivery element 110 may operate independently of the others. For example, the generator 104 may have multiple separate channels, such as four RF channels to deliver RF energy independently to the energy delivery elements 110a-d and control and monitor each energy delivery element 110a-d independently. The generator 104 may generate energy that ultimately is transmitted through the electrical lead to the one or more energy delivery elements 110.

[0038] The generator 104 may have one or more processors 402, a memory 404, a user interface 118 and/or a power source 408, as shown in FIG. 4 for example. The one or more processors 402 may be electrically coupled to the memory 404, the user interface 118 and/or the power source 408. The one or more processors 402 may include one or more controllers that obtain a temperature signal that indicates the temperature of the wall of the blood vessel and determines a heart rate based on the temperature signal. The one or more processors 402 may control a state of each of the one or more energy delivery elements 110 and the amount of energy delivered to each of the one or more energy delivery elements 110 by the power source 408 to manage the temperature at the treatment site. The one or more processors may be coupled to the memory 404 and execute instructions that are stored in the memory 404.

[0039] The generator 104 may have a memory 404. The memory may be coupled to the one or more processors 402 and store instructions that the one or more processors 402 executes. The memory 404 may include one or more of a Random Access Memory (RAM), Read Only Memory

(ROM) or other volatile or non-volatile memory. The memory 404 may be a non-transitory memory or a data storage device, such as a hard disk drive, a solid-state disk drive, a hybrid disk drive, or other appropriate data storage, and may further store machine-readable instructions, which may be loaded and executed by the one or more processors 402. The memory 404 may store one or more thresholds and/or one or more normal temperature parameter values that relate to the temperature of the one or more energy delivery elements 110 at the treatment site.

[0040] The generator 104 may have a power source 408, such as a RF generator or other electrical source. The power source 408 provides a selected form and magnitude of energy for delivery to the treatment site via the renal denervation device 102. The generator 104 may have a user interface 118, The generator 104 may receive input, such as the selected form and the magnitude of energy to be delivered to each of the one or more energy delivery elements 110, via the user interface 118.

[0041] The user interface 118 may include an input/output device that receives user input from a user interface element, a button, a dial, a microphone, a keyboard, or a touch screen. The user interface 118 may provide an output to an output device, such as a display, a speaker, an audio and/or visual indicator, or a refreshable braille display. The output device may display an alert or notification or other information to the clinician and/or to confirm status and/or commands from the clinician. The output device may be an audio output device that outputs an audio indicator that indicates the notification or information to be provided to the clinician.

[0042] FIG. 5 is a flow diagram of a process 500 for controlling the energy delivered to the one or more energy delivery elements 110 to prevent thermal damage to the tissues of the blood vessel. One or more computers or one or more data processing apparatuses, for example, the processor 402 of the therapeutic assembly 100 of FIG. 1, appropriately programmed, may implement the process 500.

[0043] The therapeutic assembly 100 may include a generator 104, which controls the delivery of energy to the one or more energy delivery elements 110 of the renal denervation device 102.

The generator 104 of the therapeutic assembly 100 receives user input that indicates initialization of the renal denervation device 102 (502). The generator 104 may receive the user input, which may be an indication to power-on the generator 104, via the user interface 118, which causes the generator 104 to power-on or initialize to deliver energy to the renal denervation device 102 and through the one or more energy delivery elements 110 to the wall of the blood vessel 304.

[0044] The therapeutic assembly 100 may obtain or determine one or more threshold temperature values (504). The therapeutic assembly 100 may obtain the one or more threshold temperature values from the memory 404. The one or more threshold temperature values may be user-configured, pre-configured or from a previous measurement or treatment session with the patient. In some implementations, the therapeutic assembly 100 determines the one or more threshold temperature values by measuring the temperature over a time period prior to delivery of the energy to the one or more energy delivery elements 110 when beginning treatment. [0045] The one or more threshold temperature values may include a threshold shutoff temperature of the one or more energy delivery elements 110. The threshold shutoff temperature may be used as an indicator to turn off, disable or otherwise power off all of the one or more energy delivery elements 110 to prevent thermal damage to the blood vessel. The one or more threshold temperature values may include one or more normal thresholds. The one or more normal thresholds may be a range that indicates an average or historically normal range of a corresponding temperature parameter of the patient when there is no stimulation or energy being delivered. For example, the one or more normal thresholds may be the frequency, magnitude and/or amplitude of the oscillation of the temperature during a time period. In another example, the one or more normal thresholds may be a range for the average, minimum and/or maximum temperature value of the patient. In another example, one or more normal thresholds may be determined for the temperature of each individual energy delivery element 110 at the various locations within the blood vessel of the patient.

[0046] Once powered-on, the therapeutic assembly 100 may deliver a first amount of energy through the one or more energy delivery elements 110 (506). The generator 104 may linearly or non-linearly ramp up or increase the amount of energy to the first amount of energy during the start-up phase until the amount of energy reaches the first amount of energy, such as approximately

6.5 W or approximately between 6 W and 7 W. The generator 104 may deliver the first amount of energy to each of the multiple energy delivery elements 110a-b when there are multiple energy delivery elements 110a-b. The multiple energy delivery elements 110a-d may be arranged to contact the wall of the blood vessel at approximately 90 degree angles relative to a longitudinal axis that runs through the center of the spiral or helical configuration when there are four energy delivery elements 110a-d and the catheter 108 is in the expanded deployed state within the blood vessel, as shown in FIG. 3 for example. The arrangement of the multiple energy delivery elements

110 may depend on the number of energy delivery elements 110. For example, when there are only three energy delivery elements 110, the energy delivery elements 110 may be arranged at approximately 120 degree angles.

[0047] During and/or after delivery of the energy, the therapeutic assembly 100 measures, detects, obtins or determines the temperature at the treatment site (508). The temperature may indicate a temperature of the one or more energy delivery elements 110, which relates to a temperature at the location of the placement of the one or more energy delivery elements 110 along the wall of the blood vessel. This provides an indication of the temperature of a region of tissue within the wall of the blood vessel.

[0048] The therapeutic assembly 100 may use the one or more sensors 112 to measure the temperature at the treatment site along the wall of the blood vessel. For example, the therapeutic assembly 100 may measure the voltage change across a voltage gap between two wires within an energy delivery element to determine the temperature.

[0049] The one or more sensors 112 may include multiple temperature sensors each positioned within a corresponding energy delivery element 110. Each of the multiple temperature sensors may independently measure the temperature at the corresponding location along the wall of the blood vessel 304 that is in contact with the temperature sensor. For example, the first energy delivery element 110a may be coupled with a first sensor 112a at a first location 302a along the blood vessel 304 and the second energy delivery element 110b may be coupled with a second sensor 112b at a second location 302b along the blood vessel 304. Other energy delivery elements 110c-d may be coupled with other sensors 112c-d at other locations 302c-d, respectively, along the blood vessel 304. The first sensor 112a may measure a first temperature 702a, as shown in FIG. 7 for example, of the first energy delivery element 110a at the first location 302a. The second sensor 112b may measure a second temperature 702b of the second energy delivery element 110b at the second location 302b, the third sensor 112c may measure a third temperature 702c of the third energy delivery element 110c at the third location 302c and the fourth sensor 112d may measure a fourth temperature 702d of the fourth energy delivery element 110d at the fourth location 302d. Any number of sensors 112 coupled to any number of energy delivery elements

110 may be used to compute the temperature at any number of locations.

[0050] The temperature at each of the multiple temperature sensors may be an instantaneous temperature and/or the temperature over a time period. The therapeutic assembly may measure or determine the temperatures using each of the multiple temperature sensors and form an aggregated temperature. The aggregate temperature may be the instantaneous temperature or the average temperature over the time period. Hereinafter, the average temperature may also refer to an exponential moving average or other weighted average. The therapeutic assembly 100 may determine different parameters from the temperature, such as a minimum temperature 704, a maximum temperature 706, an average temperature, a frequency of oscillation 708 or other parameter of the temperature from a single sensor coupled to a single energy delivery element or from an aggregation of the multiple sensors coupled the multiple energy delivery elements 110.

The calculation or determination of the different temperature parameters is further described in

FIG. 6.

[0051] The therapeutic assembly 100 determines whether the temperature is greater than or equal to a threshold temperature (510). The threshold temperature may be a threshold shutoff temperature, which may be approximately be between 80 °C - 100 °C. When the temperature is greater than or equal to the threshold temperature, the volume of tissue that is exposed to the thermally damaging temperature, which may be as low as 45 °C, may also increase. This results in a greater probability that non-target tissue will suffer irreparable damage.

[0052] The therapeutic assembly 100 compares the temperature to the threshold shutoff temperature. When the temperature is greater or equal to the threshold shutoff temperature, this may indicate there may be thermal damage to non-target tissues. And, the therapeutic assembly

100 may shut off, turn off, or otherwise disable the delivery of energy to the treatment site via the one or more energy delivery elements 110 (512). When the temperature reaches and exceeds the threshold shutoff temperature, the therapeutic assembly 100 shuts down due to hitting the threshold shutoff temperature and stops power delivery to all the energy delivery elements 110. By shutting off the delivery of energy to the treatment site, this prevents, minimizes or reduces thermal damage to the tissues of and surrounding the blood vessel including non-target tissue surrounding the blood vessel.

[0053] Otherwise when the temperature is less than the threshold shutoff temperature, the therapeutic assembly may continue to monitor any abnormalities in the temperature and may determine whether the temperature exceeds one or more normal threshold values (514). For example, the one or more abnormalities may include a temperature oscillation that exceeds a normal frequency, amplitude and/or magnitude. FIG. 6 further describes the process of determining whether the temperature exceeds one or more normal threshold values.

[0054] When there are no abnormalities in the temperature, such as when temperature is within the one or more normal threshold values, the therapeutic assembly 100 may continue to monitor, measure and/or determine the temperature of the one or more energy delivery elements 110 at the treatment site (508). When there are abnormalities in the temperature, such as when the temperature exceeds the one or more normal threshold values, the therapeutic assembly 100 controls, adjusts or otherwise modulates the delivery of energy through the one or more energy delivery elements 110 to the treatment site along the wall of the blood vessel (516).

[0055] The therapeutic assembly 100 controls, adjusts or otherwise modulates the amount of energy delivered to the treatment site to prevent thermal damage to the non-target tissue while maintaining effective treatment of the nerves. The therapeutic assembly 100 may control, adjust or otherwise modulate the amount of energy delivered to the treatment site to a second amount of energy. The second amount of energy may be different that the first amount of energy that was delivered prior to the adjustment of the delivery of the energy.

[0056] The therapeutic assembly 100 may adjust the energy at a frequency of at least 5 Hz.

The therapeutic assembly 100 may maintain the energy between approximately 6 W and 7 W, such as to maintain an average of 6.5 W, and synchronize the adjustment of the energy with the blood flow and/or heartbeat to minimize but not eliminate the temperature oscillation that occurs due to blood flow within the blood vessel during systole and diastole. For example, the second amount of energy may be a lower amount of energy of approximately 6 W, which may be delivered at the peak of diastole when the temperature is greater than or equal to a threshold temperature, and/or the second amount of energy may be a higher amount of energy of approximately 7 W, which may be delivered at the peak of systole when the temperature is less than or equal to a threshold temperature. This would modulate the temperature and may reduce the number of incidences of shutoff of the therapeutic assembly 100.

[0057] The therapeutic assembly 100 may control, adjust or otherwise modulate the amount of energy delivered to the treatment site in the aggregate by multiple energy delivery elements 110 based on the temperature aggregated and/or averaged from the multiple sensors 112. For example, the therapeutic assembly 100 may control a total amount of energy delivered by the multiple energy delivery elements 110a-d based on the average of all the temperatures aggregated from the sensors 112a-d.

[00581 In some implementations, the therapeutic assembly 100 may control, adjust or otherwise modulate the amount of energy delivered to the treatment site by each individual multiple energy delivery element 110a-d. For example, the therapeutic assembly 100 may increase or decrease the amount of energy delivered by the first energy delivery element 110a based on the temperature from the first sensor 112a, and simultaneously, may increase or decrease the amount of energy delivered by the second energy delivery element 110b based on the temperature from the second sensor 112b. The therapeutic assembly 100 may first control a total amount of energy delivered by multiple energy delivery elements 110 to partially stabilize the oscillation of the temperature, and then, control the amount of energy delivered by each individual energy delivery element 110 to further stabilize the temperature with a greater degree of fidelity. Moreover, each individual energy delivery element 110 may be ranked or weighted such that the temperature information from the energy delivery elements 110 with the lowest average or instantaneous temperature may be used to adjust or control the amount of energy delivered to the other energy delivery elements 110, which have a higher average or instantaneous temperature.

[0059] The amount of energy delivered by each of the one or more energy delivery elements

110 may also be based on the contact that the energy delivery element 110 has with the wall of the blood vessel. Since the amount of contact that the energy delivery element 110 has with the vessel wall affects the efficiency of the delivery of the energy, the therapeutic assembly 100 may increase the amount of energy delivered if the energy delivery element 110 has poor contact, such as when less than approximately 25% of the surface area of the energy delivery element 110 is in contact, with the vessel wall. Conversely, the therapeutic assembly 100 may decrease the amount of energy delivered if the energy delivery element has sufficient contact, such as when more than approximately 75% of the surface area of the energy delivery element 110 is in contact, with the vessel wall. Once the amount of energy is controlled, adjusted or otherwise modulated, the therapeutic assembly 100 delivers or provides the energy to the treatment site (518). Before, during and/or after the delivery of the energy to the treatment site, the therapeutic assembly 100 may continue to monitor, measure, obtain and/or determine the temperature at the treatment site

(508). In some implementations, the therapeutic assembly 100 may not continue to monitor, measure, obtain and/or determine the temperature at the treatment site after the delivery of the energy to the treatment site.

[0060] FIG. 6 is a flow diagram of a process 600 for adjusting the amount of energy delivered to the one or more energy delivery elements 110 to minimize or reduce temperature oscillation of the one or more energy delivery elements 110 and/or at the treatment sites along the wall of the blood vessel. One or more computers or one or more data processing apparatuses, for example, the processor 402 of the therapeutic assembly 100 of FIG. 1, appropriately programmed, may implement the process 600.

[0061] Blood flows within the renal artery is highly pulsatile, and thus, the temperatures of the energy delivery elements 110 and the tissue within the renal artery oscillates. And so, when the heart is pumping, during systole, which is the phase of the heartbeat when the heart muscle contracts and pumps blood from the chambers into the arteries, there is a pulse of blood through the blood vessel that enhances the heat transfer and cools the one or more energy delivery elements

110 and/or the one or more sensors 112, which defines a minimum temperature of the cycle.

During diastole, which is the phase of the heartbeat when the heart muscle relaxes and allows the chambers to fill with blood, blood flow is at a minimum and cooling is at its least effective, which defines a maximum temperature of the cycle. Thus, the temperature at the treatment site fluctuates, and accordingly, the therapeutic assembly 100 adjusts the amount of energy delivered to compensate for the fluctuation in temperature to minimize, but not necessarily eliminate, oscillation so that thermal damage to the tissues of the blood vessel is prevented, such as when the temperature is at a maximum, and effective treatment of the nerves continues, such as when the temperature is at a minimum. In some implementations, the oscillation may be eliminated when there is an additional device to measure the heart rate. The additional device may independently measure the heart rate by slightly elevating the temperature at a constant power and use the oscillation in the temperature, e.g., as measured at a point at or near the additional device, to direct the energy delivered to those energy delivery elements being used to modulate the tissue.

[0062] The therapeutic assembly 100 determines the temperature at the treatment site along the wall of the blood vessel, as described above (602). The therapeutic assembly 100 may determine the temperature of the energy delivery element 110 and/or the temperature at the treatment site. The temperature at the treatment site reflects or corresponds to the movement of the blood flow within the blood vessel, and thus, may be reflective or correspond to the systole or diastole phases of the heartbeat and/or the heart rate.

[0063] Once the temperature is determined at the treatment site, the therapeutic assembly 100 calculates or determines one or more temperature parameters based on the temperature (604). The one or more temperature parameters may be an instantaneous measurement or a measurement over a time period of a single energy delivery element 110a-d or multiple energy delivery elements 110a-d. The one or more temperature parameters may be a minimum, a maximum, or calculation made from the temperature. For example, the one or more temperature parameters that may be calculated include the average temperature, an exponential moving average, a rate of change in the temperature and/or a frequency, amplitude and/or magnitude of the oscillation of the temperature over a time period.

[0064] The therapeutic assembly 100 determines whether the one or more temperature parameters exceed a corresponding normal threshold (606). The therapeutic assembly 100 compares the one or more temperature parameters, such as the oscillation magnitude of the temperature, to the corresponding normal threshold. The therapeutic assembly 100 may compare a combination of temperature parameters with their corresponding normal thresholds or a single temperature parameter may be compared with its corresponding normal threshold to determine whether the energy delivered should be modulated or adjusted. For example, when the difference between the minimum and maximum temperature exceeds a normal range for the minimum and maximum temperature, such as by a standard deviation, the therapeutic assembly 100 may proceed with modulating or adjusting the energy delivered by the one or more energy delivery elements

110. Otherwise, when the one or more temperature parameters do not exceed the corresponding normal thresholds, the therapeutic assembly 100 continues to monitor or determine the temperature of the one or more energy delivery elements 110 at the corresponding treatment sites (602).

[0065] When the temperature parameters exceed the normal thresholds, the therapeutic assembly 100 determines whether the temperature is less than or equal to a low threshold temperature, such as during systole when the temperature is likely at a minimum (608). The low threshold temperature may be in a range of approximately 35 °C - 45 °C. When the temperature is below the low threshold temperature, the one or more energy delivery elements 110 may not be delivering enough energy to the location at the wall of the blood vessel to effectively innervate the nerves. [0066] When the temperature is less than or equal to the low threshold temperature, the therapeutic assembly 100 increases energy delivered through the one or more energy delivery elements 110 (610). The therapeutic assembly 100 may increase the energy delivered from a first amount of energy to a second amount of energy that is greater than the first amount of energy. The second amount of energy may be a fixed amount or a variable amount. The variable amount may be based on the difference between the temperature and the low threshold temperature, as further described below.

[0067] The therapeutic assembly 100 may increase the energy delivered through some of, all of, or a single one of the energy delivery elements 110. In some implementations, the therapeutic assembly 100 may increase the energy delivered to all of the one or more energy delivery elements

110 a partial amount, which results in a partial increase in the overall measured and/or aggregated temperature. The therapeutic assembly 100 may further identify the one or more energy delivery elements 110 that have corresponding temperatures that are below the temperatures of the other energy delivery elements 110 and further increase or adjust the amount of energy delivered through the identified one or more energy delivery elements 110.

[0068] The therapeutic assembly 100 may monitor, obtain, detect or determine the temperature before, during and/or after the therapeutic assembly 100 increases the energy delivered through the one or more energy delivery elements 110. And, the therapeutic assembly 100 may increase the amount of energy delivered to the one or more energy delivery elements 110 until the aggregate temperature and/or the temperature at each individual energy delivery element is greater than the low threshold temperature. This facilitates delivery of energy to effectively innervate the nerves.

[0069] Otherwise, when the temperature is greater than the low temperature threshold, the therapeutic assembly 100 determines whether the temperature is greater than or equal to a high threshold temperature, such as during diastole when the temperature is likely at a maximum (612).

The high threshold temperature may be in a range of approximately 55° C - 65° C. When the temperature is greater than the low threshold temperature but less than the high threshold temperature, the therapeutic assembly 100 continues to monitor and determine the temperature of the energy delivery elements 110 at the treatment sites (602). Otherwise, when the temperature is above the high threshold temperature, the therapeutic assembly 100 may be causing thermal damage to the tissues within the wall of the blood vessel and/or other tissues surrounding the blood vessel including non-target tissue. .

[0070] When the temperature is greater than the high threshold temperature, the therapeutic assembly 100 may decrease the energy delivered to the one or more energy delivery elements 110 to prevent thermal damage to the tissues (614). The therapeutic assembly 100 may decrease the energy delivered from a first amount of energy to a third amount of energy that is less than the first amount of energy. The third amount of energy may be a fixed amount or a variable amount. The variable amount may be based on the difference between the temperature and the high threshold temperature, as further described below.

[0071] The therapeutic assembly 100 may decrease the energy delivered to some of, all of, or a single one of the energy delivery elements 110. In some implementations, the therapeutic assembly 100 may decrease the energy delivered to all of the one or more energy delivery elements

1-10 a partial amount, which results in a partial decrease in the overall measured and/or aggregated temperature. The therapeutic assembly 100 may further identify the one or more energy delivery elements 110 that have corresponding temperatures that are above the temperatures of the other energy delivery elements 110 and further decrease or adjust the amount of energy delivered through the identified one or more energy delivery elements 110. The therapeutic assembly 100 may monitor, detect and/or determine the temperature before, during and/or after the therapeutic assembly 100 decreases the energy delivered through the one or more energy delivery elements

110. And, the therapeutic assembly 100 may decrease the amount of energy delivered to the one or more energy deliveiy elements 110 until the aggregate temperature and/or the temperature at each individual energy delivery element is less than the high threshold temperature.

[0072] The therapeutic assembly 100 may increase or decrease the amount of energy delivered based on the difference between the temperature and the low threshold or high threshold, respectively. The increase or decrease of the amount of energy delivered may be directly proportional to the magnitude of the difference between the temperature and the low threshold or high threshold, respectively. Once the therapeutic assembly 100 increases or decreases the amount of energy delivered, the therapeutic assembly 100 may continue to monitor, detect, obtain and/or determine the temperature at the treatment site to determine whether further adjustments to the delivery of the energy may or may not be warranted. In some implementations, the therapeutic assembly 100 may not continue to monitor, measure, obtain and/or determine the temperature after the increase or decrease of the amount of energy that is delivered to the treatment site.

10073] Exemplary embodiments of the invention have been disclosed in an illustrative style.

Accordingly, the terminology employed throughout should be read in a non-limiting manner.

Although minor modifications to the teachings herein will occur to those well versed in the art, it shall be understood that what is intended to be circumscribed within the scope of the patent warranted hereon are all such embodiments that reasonably fall within the scope of the advancement to the art hereby contributed, and that that scope shall not be restricted, except in light of the appended claims and their equivalents.

Claims

CLAIMS What is claimed is:

1. A therapeutic assembly for renal denervation, comprising: a first energy delivery element configured to deliver energy to a treatment site; a first sensor coupled to the first energy delivery element and configured to measure a first temperature of the first energy deliveiy element; and a processor coupled to the first sensor and the first energy delivery element and configured to: increase the delivery of energy to the treatment site when the first temperature is less than or equal to a first threshold temperature, and adjust the delivery of energy to the treatment site when the first temperature is greater than or equal to a second threshold temperature.

2. The therapeutic assembly of claim 1, wherein to adjust the delivery of energy to the treatment site when the first temperature is greater than or equal to the second threshold temperature, the processor is configured to: adjust the delivery of energy to the treatment site from a first amount of energy to a second amount of energy, wherein the first amount of energy is different than the second amount of energy.

3. The therapeutic assembly of claim 2, wherein the processor is further configured to: provide, using the first energy delivery element, the first amount of energy to the treatment site prior to adjusting the delivery of energy to the treatment site; and provide, using the first energy delivery element, the second amount of energy to the treatment site after adjusting the delivery of energy to the treatment site.

4. The therapeutic assembly of claim 1, wherein to adjust the delivery of energy to the treatment site when the first temperature is greater than or equal to the second threshold temperature, the processor is configured to turn off, disable or otherwise power off the first energy delivery element.

5. The therapeutic assembly of claim 1, further comprising: a second energy delivery element configured to deliver a second amount of energy to a second location of the treatment site, wherein the first energy delivery element is configured to deliver a first amount of energy to a first location of the treatment site.

6. The therapeutic assembly of claim 5, wherein to adjust the delivery of energy to the treatment site when the first temperature is greater than or equal to the second threshold temperature the processor is configured to: decrease the first amount of energy delivered by the first energy delivery element to the first location of the treatment site; and decrease the second amount of energy delivered by the second energy delivery element to the second location of the treatment site.

7. The therapeutic assembly of claim 1, further comprising: a catheter coupled to the first sensor and the first energy delivery element and configured to be intravascularly inserted into the vessel, wherein the vessel is a renal artery and wherein the first sensor is coupled to the first energy delivery element.

8. The therapeutic assembly of claim 7, further comprising: a radio frequency generator configured to deliver the energy to the first energy delivery element, wherein the energy is a radiofrequency (RF) signal, wherein the first energy delivery element is an electrode.

9. A therapeutic assembly for renal denervation, comprising: a first electrode. configured to deliver energy to a treatment site; a first temperature sensor coupled to the first electrode and configured to measure a first temperature of the first electrode; and a processor coupled to the first temperature sensor and the first electrode and configured to: increase the delivery of energy to the treatment site when the first temperature is less than or equal to a first threshold temperature, and decrease the delivery of energy to the treatment site when the first temperature is greater than or equal to a second threshold temperature.

10. The therapeutic assembly of claim 9, wherein the processor is further configured to: provide, using the first electrode, a first amount of energy to the treatment site prior to decreasing the delivery of energy to the treatment site; and provide, using the first electrode, a second amount of energy to the treatment site after adjusting the delivery of energy to the treatment site, wherein the second amount of energy is different than the first amount of energy.

11. The therapeutic assembly of claim 10, wherein the second amount of energy is less than the first amount of energy.

12. The therapeutic assembly of claim 9, further comprising: a second electrode configured to deliver a second amount of energy to a second location of the treatment site, wherein the first electrode is configured to deliver a first amount of energy to a first location of the treatment site.

13. The therapeutic assembly of claim 12, wherein to decrease the delivery of energy to the treatment site when the first temperature is greater than or equal to the second threshold temperature the processor is configured to: decrease the first amount of energy delivered by the electrode from the first amount of energy to a third amount of energy; and decrease the second amount of energy delivered by the second energy delivery element to a fourth amount of energy.

14. The therapeutic assembly of claim 13, wherein the third amount of energy is different than the fourth amount of energy.

15. The therapeutic assembly of claim 9, wherein the first temperature sensor is configured to measure the first temperature of the first electrode during a first time period and a second temperature of the first electrode during a second time period.

16. The therapeutic assembly of claim 15, wherein the processor is configured to decrease the delivery of energy to the treatment site when the first temperature is greater than or equal to the second threshold temperature during the first time period and increase the delivery of energy to the treatment site when the first temperature is less than the first threshold temperature during the second time period.

17. A method for modulating energy delivered during renal denervation, comprising: determining, by a processor and using a sensor, a temperature of an electrode at a treatment site during a first time period; determining, by the processor, that the temperature of the electrode is greater than or equal to a threshold temperature during the first time period; and decreasing, by the processor, an amount of energy delivered to the treatment site when the temperature of the electrode is greater than or equal to the threshold temperature.

18. The method of claim 17, further comprising: determining, by the processor and using a sensor, a temperature of the electrode at the treatment during a second time period; and increasing, by the processor, the amount of energy delivered to the treatment site when the temperature of the electrode is less than a second threshold.

19. The method of claim 17, further comprising: determining, by the processor, a difference between the temperature of the electrode and the threshold temperature.

20. The method of claim 19, wherein decreasing the amount of energy delivered to the treatment site is based on the difference between the temperature of the electrode and the threshold temperature.