Neurostimulation waveforms for increased tissue activation across vascular walls

Abstract

The present disclosure provides a method of performing and evaluating a treatment procedure, the method comprising: navigating a treatment device to a target tissue; transitioning the treatment device from a first linear configuration to a second deployed configuration such that a plurality of electrodes on the treatment device engage the target tissue; applying a pulse of neurostimulation energy having at least two phases to the target tissue via the plurality of electrodes, the neurostimulation energy comprising an anode phase and a cathode phase, where the phase of neurostimulation is switched from anode to cathode or from cathode to anode for each consecutive pulse; observing a physiological response to the nerve stimulation energy indicative of a nerve response; performing denervation on the nerves of the target tissue; and applying the neurostimulation energy to the target tissue, wherein less than a physiological response than a threshold indicates successful denervation of the nerves of the target tissue.

Description

Technical Field

[0001] The present disclosure relates to systems and methods that enable positioning of therapeutic devices within luminal tissue to enhance ablation during a therapeutic procedure.In certain aspects, the present disclosure relates to methods and systems for denervating nerves in or around vascular tissue. Background Art

[0002] Catheters have been proposed for various medical procedures. For example, catheters can be configured to deliver neuromodulation (e.g., denervation) therapy to target tissue sites to change the activity of nerves at or near target tissue sites. Nerves can be, for example, sympathetic or parasympathetic. The sympathetic nervous system (SNS) is the main involuntary body control system usually associated with stress response. Chronic overactivation of SNS is a maladaptive reaction that can drive the progression of many disease states. For example, overactivation of renal SNS has been confirmed in experiments and humans as a possible cause of the complex pathophysiology of arrhythmias, hypertension, volume overload states (e.g., heart failure) and progressive nephropathy.

[0003] Percutaneous renal denervation is a minimally invasive procedure that can be used to treat hypertension and other diseases caused by overactivation of the SNS. During a renal denervation procedure, clinicians deliver stimulation or energy, such as radiofrequency, ultrasound, cooling, or other energy, to the treatment site to reduce the activity of the nerves around the blood vessels. The stimulation or energy delivered to the treatment site can provide various therapeutic effects by altering sympathetic nerve activity. Summary of the invention

[0004] According to the present disclosure, a method for executing and evaluating a treatment procedure includes: navigating a treatment device to a target tissue; transforming the treatment device from a first linear configuration to a second helical configuration so that a plurality of electrodes on the treatment device engage with the target tissue; applying a pulse of neural stimulation energy having at least two phases to the target tissue via the plurality of electrodes, wherein each pulse of the neural stimulation energy includes an anode phase and a cathode phase, and for each consecutive pulse, switching a leading phase of the neural stimulation energy from anode to cathode or from cathode to anode; observing a physiological response to the pulse of the neural stimulation energy that exceeds a threshold and indicates a neural response; denervating the nerves of the target tissue; and applying a pulse of the neural stimulation energy to the target tissue, wherein a physiological response less than the threshold indicates successful denervation of the nerves of the target tissue.

[0005] In various aspects, the physiological response can be blood pressure or vascular stiffness.

[0006] In other aspects, the target tissue can be one or more of a renal artery, a visceral artery, or a hepatic artery.

[0007] In certain aspects, during the anodic phase, energy may be applied to a first electrode of the plurality of electrodes and received by a second electrode of the plurality of electrodes.

[0008] In other aspects, during the cathodic phase, energy can be applied to a second electrode of the plurality of electrodes and received by a first electrode of the plurality of electrodes.

[0009] In various aspects, energy may be applied to or received by two or more electrodes of the plurality of electrodes during either the anodic phase or the cathodic phase.

[0010] In other aspects, denervation can be achieved by applying monopolar energy to the target tissue via multiple electrodes.

[0011] In certain aspects, denervation can be achieved by a therapy modality selected from the group consisting of radiofrequency ablation, microwave ablation, ultrasound ablation, cryoablation, and chemical ablation.

[0012] In various aspects, the neural stimulation energy may include a frequency between about 10 Hz and 30 Hz, a pulse width between about 2 ms and 10 ms, a voltage between about 5 V and 30 V, and a current between about 2 mA and 500 mA.

[0013] In certain aspects, neural stimulation energy can be multi-phasic.

[0014] In various aspects, the neural stimulation energy can be biphasic or triphasic.

[0015] According to another aspect of the present disclosure, a method for evaluating a target location for therapy includes: applying a pulse of neural stimulation to tissue at the target location, wherein the neural stimulation pulse includes an anodic phase and a cathodic phase; for each consecutive pulse, switching the phase of the neural stimulation pulse from anode to cathode or from cathode to anode; and observing a physiological response to the neural stimulation pulse, wherein a response exceeding a threshold indicates that the neural response indicates that the target location is a candidate for application of therapy.

[0016] In various aspects, the physiological response can be blood pressure or vascular stiffness.

[0017] In other aspects, the target location can be one or more of the renal arteries, visceral arteries, or hepatic arteries.

[0018] In certain aspects, during the anodal phase, neural stimulation may be applied to a first electrode of the plurality of electrodes and received by a second electrode of the plurality of electrodes.

[0019] In other aspects, during the cathodic phase, neural stimulation can be applied to a second electrode of the plurality of electrodes and received by a first electrode of the plurality of electrodes.

[0020] In various aspects, neural stimulation may be applied to or received by two or more electrodes of the plurality of electrodes during either the anodic phase or the cathodic phase.

[0021] In certain aspects, the method may include navigating the diagnostic device to the target location.

[0022] In other aspects, the method may include transitioning a diagnostic device from a first configuration to a second configuration such that a plurality of electrodes on the diagnostic device engage tissue at a target location.

[0023] In various aspects, the diagnostic device can be transitioned from a linear configuration to a helical configuration to place the electrode into engagement with tissue at a target location.

[0024] In certain aspects, the method may include inflating the balloon to place the electrode into engagement with tissue at the target location.

[0025] In other aspects, the diagnostic device can be a guide catheter having a plurality of electrodes disposed thereon for delivering neural stimulation to target tissue.

[0026] In various aspects, the method may include placing at least two electrodes of a plurality of electrodes of a guide catheter into engagement with tissue at a target location.

[0027] In other aspects, the method may include applying a denervation therapy to the target tissue, the denervation therapy selected from the group consisting of radiofrequency ablation, microwave ablation, ultrasound ablation, cryoablation, and chemical ablation.

[0028] In certain aspects, neural stimulation energy can be multi-phasic.

[0029] In various aspects, the neural stimulation energy can be biphasic or triphasic.

[0030] According to another aspect of the invention, a system for performing diagnostic and therapeutic procedures includes: a catheter comprising a plurality of electrodes and configured for placement proximate to a target tissue; and an energy source operably coupled to the catheter, the energy source having a diagnostic mode and a denervation mode, in which pulses of neural stimulation energy are generated for delivery in a bipolar manner between at least two of the plurality of electrodes, the pulsed neural stimulation energy comprising an anode phase and a cathode phase, and the energy source is configured to switch the phase of the pulsed neural stimulation energy from anode to cathode or from cathode to anode for each consecutive pulse, and in which monopolar energy is generated for delivery by the plurality of electrodes to denervate nerves of the target tissue in the denervation mode.

[0031] In various aspects, the catheter can have a first configuration and a second configuration, wherein in the second configuration, a plurality of electrodes on the catheter engage tissue at the target tissue.

[0032] In certain aspects, the first configuration can be a linear configuration for navigating to the target tissue and the second configuration is a helical configuration that places the plurality of electrodes into engagement with tissue at the target tissue.

[0033] In other aspects, the system can include a balloon disposed on the catheter, wherein inflation of the balloon places the plurality of electrodes into engagement with tissue at the target tissue.

[0034] According to another aspect of the present disclosure, a system for performing diagnostic and therapeutic procedures includes: a catheter comprising a plurality of electrodes and configured for placement proximate to a target tissue; an energy source operably coupled to the catheter, the energy source generating pulses of neural stimulation for delivery in a bipolar manner between at least two of the plurality of electrodes, the pulsed neural stimulation energy comprising an anode phase and a cathode phase, and the energy source configured to switch the phase of the pulsed neural stimulation energy from anode to cathode or from cathode to anode for each consecutive pulse; and a therapy source coupled to the catheter for delivering denervation therapy to denervate nerves of the target tissue.

[0035] In various aspects, the therapy source may be selected from the group consisting of: a cryogenic source for delivering cryogenic media, an RF generator for generating monopolar radiofrequency energy, a microwave generator for generating microwave energy, and a chemical source for delivering chemical media.

[0036] In various aspects, the system can include a balloon disposed on the catheter, wherein inflation of the balloon places a plurality of electrodes into engagement with tissue at the target tissue.

[0037] In certain aspects, the therapy source can be a cryogenic source for delivering a cryoablative agent, wherein the balloon is filled with the cryoablative agent.

[0038] In other aspects, the energy source can be integrated with the therapy source.

[0039] In certain aspects, the catheter can include a second plurality of electrodes configured for placement proximate to the target tissue, the second plurality of electrodes coupled to a therapy source for delivering denervation therapy to the target tissue.

[0040] In various aspects, the energy source and the therapy source may each be coupled to a plurality of electrodes such that the plurality of electrodes deliver neural stimulation energy to the tissue in a diagnostic mode and deliver denervation therapy to the tissue in a denervation mode.

[0041] In certain aspects, the catheter can have a first configuration and a second configuration, wherein in the second configuration, a plurality of electrodes on the catheter engage tissue at the target tissue.

[0042] In other aspects, the first configuration can be a linear configuration for navigating to the target tissue and the second configuration is a helical configuration that places the plurality of electrodes into engagement with tissue at the target tissue.

[0043] According to another aspect of the present disclosure, a system for performing diagnostic and therapeutic procedures includes a catheter and a workstation, the catheter including multiple electrodes and configured for placement near a target tissue, the workstation operably coupled to the catheter, the workstation including a memory and a processor, the memory storing instructions that, when executed by the processor, cause the processor to: apply pulses of neural stimulation energy having at least two phases to the target tissue via the multiple electrodes, wherein each pulse of the neural stimulation energy includes an anode phase and a cathode phase, and for each consecutive pulse, switch the phase of the neural stimulation energy from anode to cathode or from cathode to anode; observe a physiological response to the pulse of the neural stimulation energy that exceeds a threshold and indicates a neural response; denervate the nerves of the target tissue; and apply the pulse of the neural stimulation energy to the target tissue, wherein a physiological response less than the threshold indicates successful denervation of the nerves of the target tissue.

[0044] In various aspects, the system can include an energy source operably coupled to the catheter, the energy source configured to generate a therapy modality selected from the group consisting of radiofrequency ablation, microwave ablation, ultrasound ablation, cryoablation, and chemical ablation.

[0045] In other aspects, the energy source is configured to generate the neural stimulation energy when in the diagnostic mode and to generate the therapy modality when in the denervation mode.

[0046] In certain aspects, the neural stimulation energy may include a frequency between about 10 Hz and 30 Hz, a pulse width between about 2 ms and 10 ms, a voltage between about 5 V and 30 V, and a current between about 2 mA and 500 mA.

[0047] In other aspects, the system can include a balloon disposed on the catheter, wherein inflation of the balloon places the plurality of electrodes into engagement with the target tissue.

[0048] Further disclosed herein is a method for executing and evaluating a treatment procedure, the method comprising: navigating a treatment device to a target tissue; transitioning the treatment device from a first linear configuration to a second expanded configuration such that a plurality of electrodes on the treatment device engage the target tissue; applying pulses of neural stimulation energy having at least two phases to the target tissue via the plurality of electrodes, the neural stimulation energy comprising an anodic phase and a cathodic phase, wherein for each successive pulse, the phase of the neural stimulation is switched from anode to cathode or from cathode to anode; observing a physiological response to the neural stimulation energy indicative of a neural response; denervating the nerve of the target tissue; and applying the neural stimulation energy to the target tissue, wherein a physiological response less than a threshold value indicates successful denervation of the nerve of the target tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Various aspects and embodiments of the present disclosure are described below with reference to the accompanying drawings, in which:

[0050] Figure 1 is a schematic diagram of a therapy system provided according to the present disclosure;

[0051] Figure 2 yes Figure 1 A schematic diagram of a workstation of a therapy system;

[0052] Figure 3 yes Figure 1 A perspective view of a treatment device of a therapy system;

[0053] Figure 4 yes Figure 3 A perspective view of a therapeutic device shown advanced within a portion of a patient's anatomy and in a deployed state;

[0054] Figure 5 According to the present disclosure Figure 1 a perspective view of another embodiment of a therapeutic device of a therapy system of the invention; and

[0055] Figure 6 is a flow chart illustrating a method of performing a treatment protocol in accordance with the present disclosure. DETAILED DESCRIPTION

[0056] The present disclosure relates to treatment systems and methods for denervation or neuromodulation of nerves, such as sympathetic nerves, or in certain embodiments parasympathetic nerves, particularly unmyelinated nerve fibers in and around blood vessels and other luminal tissues. In order to enhance the efficacy of denervation of nerves, the treatment system is configured to apply neural stimulation to blood vessels or other luminal tissues with multi-phase (e.g., biphasic, triphasic, etc.) pulse waveforms. In one non-limiting embodiment, and as generally described herein, neural stimulation includes a biphasic waveform, wherein each pulse of the biphasic waveform has an anode leading phase and a cathode trailing phase, or vice versa. In at least one embodiment, the treatment system is configured to alternate the leading phase of each pulse of the biphasic waveform during the application of neural stimulation, so that, for example, the first pulse includes an anode leading phase and a cathode trailing phase, the subsequent second pulse includes a cathode leading phase and an anode trailing phase, and the subsequent third pulse returns to the anode leading phase and the cathode trailing phase. The leading phase of each pulse of the biphasic waveform alternates during the duration of applying neural stimulation. As a result, neural responses to neural stimulation are enhanced compared to continuous first phase biphasic waveforms and monophasic waveforms known in the art. This, in turn, increases the likelihood of stimulating neural tissue and reduces the amount of time required to identify suitable neural tissue for denervation therapy. Further application of neural stimulation facilitates accurate determination of the suitability of a location for receiving therapy because the alternating biphasic waveforms described herein stimulate a greater amount of neural tissue. Although generally described throughout this disclosure as having a biphasic waveform, as described above, the neural stimulation applied to the tissue may include any multiphasic waveform in which one or more of the phases are reversed for each consecutive pulse without departing from the scope of the present disclosure.

[0057] The therapeutic device contemplated in the present disclosure can apply one or more therapeutic modalities in a variety of therapeutic modalities. For example, the therapeutic modalities considered within the scope of the present disclosure include monopolar or bipolar radiofrequency, microwave, cryogenics, ultrasound, chemistry and other modalities yet to be developed. Any of these therapeutic modalities can be incorporated into a therapeutic device (such as a catheter), which is configured to navigate to a desired position in the patient's body. A catheter configured to deliver one or more of these therapeutic modalities can be navigated percutaneously, such as via femoral artery navigation, to reach the blood vessels of the aorta, including the celiac artery, the hepatic artery, the visceral artery, the mesenteric artery, and other arteries weakened by sympathetic nerves or close to one or more sympathetic ganglia. Such a catheter can also be placed laparoscopically in one or more of the above-identified blood vessels, or in another luminal tissue, without departing from the scope of the present disclosure.

[0058] The therapeutic devices described herein are also configured to deliver neural stimulation to blood vessels or other luminal tissues. Such neural stimulation can take a variety of forms (e.g., magnitude, frequency, duration), however, the neural stimulation signal itself is a multi-phase pulse waveform (e.g., biphasic or triphasic pulse). The amplitude, frequency, pulse width and / or duration of the neural stimulation can be selected and / or modified to ensure stimulation of target nerves (e.g., unmyelinated nerve fibers) of periluminal tissue without damaging luminal tissue or nerves in or around luminal tissue or causing excessive vasoconstriction around the therapeutic device (e.g., inhibiting movement of the therapeutic device in the luminal tissue).

[0059] As described above, one of the goals of neural stimulation is to identify a portion of a blood vessel or luminal tissue close to a sympathetic nerve that is a candidate for denervation therapy. In this way, the physiological response to neural stimulation applied to the luminal tissue, such as increased blood pressure or increased luminal tissue hardness, is measured and / or observed. If no response is observed or an insufficient response is observed, the position of the therapeutic device in the blood vessel or luminal tissue can be adjusted, for example, proximal or distal, or clockwise or counterclockwise, and neural stimulation is applied again and the physiological response is measured and / or observed again. The physiological response to neural stimulation can be compared with one or more predetermined thresholds, so that blood pressure or tissue hardness exceeds the threshold to indicate that the tissue is a candidate for denervation, and blood pressure or tissue hardness is below the threshold to indicate that the tissue may not be a candidate for denervation. In an embodiment, neural stimulation can be applied at various positions and / or orientations within the blood vessel or luminal tissue, and the physiological response is measured and recorded at each position. The position and / or orientation with the strongest physiological response can be selected as the position and / or orientation where denervation will be most effective.

[0060] Neurostimulation may be delivered to a blood vessel or luminal tissue via two or more energy delivery elements or electrodes disposed in a spaced relationship from one another. These electrodes may be disposed on the outer surface of a therapy catheter, on a balloon, on a separate treatment device (such as a guide catheter, a guide wire, etc.). The electrodes may deliver neurostimulation to a blood vessel or luminal tissue independently of one another, such that during the anodic phase of a biphasic pulse, neurostimulation is applied to the blood vessel via a first electrode of the electrodes and received by a second electrode, and during the cathodic phase of a biphasic pulse, neurostimulation is applied to the target tissue via the second electrode and received by the first electrode. In an embodiment, during the anodic phase or the cathodic phase of a bipolar pulse, neurostimulation is applied by two or more of the electrodes or received by two or more of the electrodes.

[0061] The treatment device can be coupled to a therapy source and a neural stimulation source, although it is contemplated that the therapy source and the neural stimulation source can be the same and capable of generating both therapy and neural stimulation. For example, the electrical generator can be configured to generate biphasic pulses to be supplied to the neural stimulation application portion of the treatment device and to supply monopolar RF energy to the therapy application portion, although it is contemplated that the neural stimulation application portion and the therapy application portion of the treatment device can be the same such that neural stimulation and monopolar RF energy can be applied to tissue via the same electrode at different points in time. Additionally, or alternatively, the modalities used for therapy and neural stimulation can be similar, as described above, or very different, such as a combination of biphasic neural stimulation and cryoablation therapy. Any combination of the above-described therapy modalities and neural stimulation modalities is contemplated within the scope of the present disclosure.

[0062] According to aspects of the present disclosure, a therapeutic device can be navigated within a vessel or luminal tissue in one configuration (e.g., a linear configuration) and, once positioned at a desired location, deployed or otherwise actuated to achieve a second configuration (e.g., an inflated balloon, an deployed needle, a shape memory spiral shape, etc.). The second configuration can be achieved before or after the application of neural stimulation. Regardless of when it is applied, according to the present disclosure, the application of neural stimulation can be performed multiple times before, during, and after the application of therapy. In this way, the application of neural stimulation can also be used to evaluate the effectiveness of a denervation procedure. After successful denervation, the application of neural stimulation can result in a limited absence of a physiological response because the nerves that stimulated the physiological response have been severed and cannot trigger any such response.

[0063] For ease of description, most of the descriptions in the following description focus on the implementation of electrical stimulation and RF denervation. Those skilled in the art will recognize that the methods and systems described herein may employ any of the therapy modalities and / or neurostimulation modalities described herein. Similarly, the following description focuses on navigating to the renal artery and applying neurostimulation and / or therapy to the renal artery to denervate the sympathetic nerves in, around, and near the renal artery or, in certain embodiments, the parasympathetic nerves. However, the present disclosure is not limited thereto and may be used to denervate nerves accessible to any of the blood vessels described herein that may be accessed via other luminal tissues (e.g., bile ducts).

[0064] Now turning to the attached figure, Figure 1A therapy system is shown that is provided in accordance with the present disclosure and is generally identified by reference numeral 10. As will be described in further detail below, therapy system 10 enables navigating a therapy device 50 to a desired location within a patient's anatomy (e.g., a renal artery of the patient), delivering neural stimulation to tissue within the renal artery, observing a physiological response to the application of the neural stimulation to the tissue, adjusting the position of the therapy device within the renal artery based on the physiological response, reapplying neural stimulation to the tissue at the adjusted location, applying denervation therapy to tissue within the renal artery to denervate sympathetic nerves within the tissue, and delivering neural stimulation to the denervated tissue, observing a physiological response to the neural stimulation and evaluating the efficacy of the denervation therapy.

[0065] The therapy system 10 includes a workstation 20, a treatment device 50 operably coupled to the workstation 20, and an imaging device 70, which may be operably coupled to the workstation 20. A patient "P" is shown lying on an operating table 12 with the treatment device 50 inserted through a portion of the patient's femoral artery, although it is contemplated that the treatment device 50 may be inserted into any suitable portion of the patient's vascular network that is in fluid communication with a desired vessel for therapy. Although generally described as having one treatment device 50, it is contemplated that the treatment system 10 may employ any suitable number of treatment devices 50. The treatment devices 50 may employ the same or different therapy modalities and may be operably coupled to the workstation 20. Additionally, the treatment device 50 may employ a guidewire 64 or a guide catheter 62 without departing from the scope of the present disclosure.

[0066] continue Figure 1 And also refer to Figure 2 , workstation 20 includes a computer 22, a therapy source 24 (e.g., an RF generator, a microwave generator, an ultrasound generator, a cryogenic medium source, a chemical source, etc.) operably coupled to computer 22, and a neural stimulation source 24a operably coupled to computer 22. Although generally described as being separate from therapy source 24, it is contemplated that stimulation source 24a may be integrated within therapy source 24, as described above, and that therapy source 24 may generate both therapy modalities and neural stimulation modalities.

[0067] The computer is coupled to a display 26 configured to display one or more user interfaces 28. The computer 22 may be a desktop computer or a tower configuration with the display 26, or may be a laptop or other computing device. The computer 22 includes a processor 30 that executes software stored in a memory 32. The memory 32 may store one or more application programs 34 and / or algorithms 44 to be executed by the processor 30. A network interface 36 enables the workstation 20 to communicate with various other devices and systems via the Internet. The network interface 36 may connect the workstation 20 to the Internet via a wired or wireless connection. Additionally or alternatively, communication may be via an ad hoc network that enables communication with a wide area network (WAN) and / or a local area network (LAN). or wireless network. The network interface 36 can be connected to the Internet via one or more gateways, routers, and network address translation (NAT) devices. The network interface 36 can communicate with a cloud storage system 38, in which additional data, image data, and / or video can be stored. The cloud storage system 38 can be remote from the hospital or in a hospital building, such as in a control or hospital information technology room. It is contemplated that the cloud storage system 38 can also be used as a host for more robust analysis of acquired images (e.g., fluoroscopy, computed tomography (CT), magnetic resonance imaging (MRI), cone beam computed tomography (CBCT), etc.), data, etc. (e.g., additional or enhanced data for analysis and / or comparison). The input module 40 receives input from an input device, such as a keyboard, a mouse, a voice command, an energy source controller (e.g., a foot pedal or handheld remote control device that enables a clinician to start, terminate, and optionally adjust various operating characteristics of the therapy source and / or the neural stimulation source (including but not limited to power delivery)), etc. Output module 42 connects processor 30 and memory 32 to various output devices, such as display 26. In an embodiment, display screen 26 may be a touch screen display.

[0068] The therapy source 24 generates and outputs one or more of RF energy (monopolar or bipolar), microwave energy, ultrasound energy, cryogenic medium, or chemical ablative medium via an automatic control algorithm 44 stored on the memory 32 and / or under the control of a clinician. As can be appreciated, the therapy generated and / or output by the therapy source 24 changes the temperature of the tissue (e.g., increases or decreases the temperature) to achieve the desired denervation of the nerve. The therapy source 24 can be configured to generate energy and / or therapy of a selected modality and magnitude for delivery to the treatment site via the treatment device 50, as will be described in further detail below. The therapy source 24 can monitor the voltage and current applied to the target tissue via the treatment device 50, and monitor the temperature of the target tissue or tissue near the target tissue and / or a portion of the treatment device 50.

[0069] The neurostimulation source 24a generates a neurostimulation having a biphasic waveform and an energy level less than the therapy generated by the therapy source, such that the neurostimulation generated by the neurostimulation source 24a does not denervate the target tissue. Instead, the neurostimulation source 24a generates a neurostimulation that is capable of achieving a response from the nerve that indicates a tissue that would be a candidate for denervation, such as increased blood pressure, increased vascular stiffness, pulse wave velocity, increased pressure, heart rate changes, etc. The neurostimulation source 24a generates a biphasic waveform in which the lead phase of each consecutive pulse of the biphasic waveform is switched or otherwise reversed. In this manner, a biphasic waveform having an initial pulse with an anode lead phase and a cathode post phase will be followed by a second pulse with a cathode lead phase and an anode post phase, which will be followed by a third pulse that returns to the anode lead phase and cathode post phase, and so on. Alternatively, a biphasic waveform having an initial pulse with a cathodic lead phase and an anodic post phase will be followed by a second pulse with an anodic lead phase and a cathodic post phase, which will be followed by a third pulse returning to a cathodic lead phase and an anodic post phase. As can be appreciated, the lead phase of each pulse of the biphasic waveform alternates over the duration of the neural stimulation applied to the target tissue.

[0070] As described above, the amplitude, frequency, pulse width and / or duration of the neural stimulation can be selected and / or modified to ensure neural stimulation of the sympathetic nerves of the luminal tissue without damaging the luminal tissue or nerves in or around the luminal tissue or causing excessive vasoconstriction around the therapeutic device (e.g., inhibiting movement of the therapeutic device within the luminal tissue). As will be appreciated, the pulse duration (pulse width) of the biphasic pulse can be modified to ensure that the anodal stimulation of the tissue is maintained, because at certain pulse durations, the area of ​​anodal stimulation can dissipate or otherwise disappear, resulting in less neural stimulation area. In one non-limiting embodiment, the neural stimulation source 24a generates a biphasic waveform having a frequency between about 10 Hz and 30 Hz, a voltage between about 5 V and 30 V, a current between about 2 mA and 500 mA, and a pulse width between about 2 ms and 10 ms. It is contemplated that in embodiments targeting unmyelinated nerve fibers, the pulse width of the biphasic waveform can be between about 10 ms and 120 ms.

[0071] Figure 3 and Figure 4One embodiment of a treatment device 50 according to the present disclosure is depicted. The treatment device 50 includes an elongated shaft 52 having a handle 54 disposed on a proximal end portion 52a of the elongated shaft 52. The treatment device 50 includes a treatment assembly 56 at which one or more therapy electrodes 58 are located. The elongated shaft 52 of the treatment device 50 is configured to be advanced within a portion of a patient's vasculature, such as a femoral artery or other suitable portion of a patient's vascular network in fluid communication with a patient's renal artery. In an embodiment, the treatment assembly 56 is configured to be extended from an initial undeployed state ( Figure 3 ) into a second deployed or expanded configuration, wherein the therapeutic assembly 56 forms a generally helical and / or spiral configuration ( Figure 4 ) for delivering therapy at the treatment site and providing therapeutically effective electrically and / or thermally induced renal neuromodulation. In this manner, when in the second expanded configuration, the therapeutic assembly 56, and in particular the individual electrodes 58, press against or otherwise contact the wall of the patient's vasculature tissue. Although generally described as transitioning to a helical and / or spiral configuration, it is contemplated that the therapeutic assembly 56 may be deployed in other configurations without departing from the scope of the present disclosure. In addition, the therapeutic device 50 may be configurable, for example, using one or more pull wires (not shown) to adjust the configuration to facilitate contact between the electrodes 58 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 on the design requirements of the therapeutic device 50 or the location where therapy is to be applied.

[0072] like Figure 4 As depicted, the elongated shaft 52 can be configured to be received within a portion of a guide catheter or guide sheath (such as a 6F guide catheter) 62 that is used to navigate the treatment device 50 to a desired location, at which point the guide catheter 62 is retracted to expose a treatment portion 56 of the treatment device 50. As described above, retraction of the guide catheter 62 can enable the treatment portion 56 to transition from a first, undeployed configuration to a second, deployed or expanded configuration.

[0073] The elongated shaft 52 of the treatment device 50 may further include an aperture (not shown) configured to slidably receive a guide wire 64 over which the treatment device 50 is advanced, alone or in combination with the guide catheter 62. In this manner, the guide wire 64 is utilized to guide the treatment device 50 to the target tissue using an over the guide wire (OTW) or rapid exchange (RX) technique, at which point the guide wire may be partially or completely removed from the treatment device 50, enabling the treatment device 50 to be moved from the first undeployed configuration ( Figure 3 ) into a second expanded or expanded configuration ( Figure 4As described elsewhere herein, the therapeutic device 50 can be automatically (e.g., via shape memory alloys, etc.) or manually (e.g., via pull-wires, guidewire manipulation, etc. controlled by a clinician) transformed from a first, undeployed configuration to a second, deployed configuration.

[0074] Continue to refer Figure 3 and Figure 4 In an embodiment where the treatment device 50 is an RF ablation catheter, the treatment portion 56 includes one or more electrodes 58 disposed on an outer surface thereof, the one or more electrodes being configured to contact a portion of the patient's vascular tissue when the treatment device 50 is placed in the second expanded configuration. As shown herein, the treatment device 50 includes four electrodes 58. However, the present disclosure is not limited in this regard, and the treatment device 50 may have more or fewer electrodes 58 without departing from the scope of the present disclosure. Those skilled in the art will recognize that the electrodes 58 may be replaced with ultrasonic transducers, microwave antennas, ports for delivering cryoablative or chemical media, and other instruments and / or ablation and denervation modalities without departing from the scope of the present disclosure.

[0075] As shown, electrodes 58 are disposed in a spaced relationship along the length of the treatment device 50 to form a treatment portion 56. As will be appreciated, these electrodes 58 are in communication with a therapy source 24 that generates, for example, monopolar RF energy to denervate the sympathetic nerves of the associated blood vessels. Additionally or alternatively, the electrodes 58 may deliver RF energy independently of one another (e.g., monopolar), simultaneously, selectively, sequentially, and / or between any desired combination of electrodes 58 (e.g., bipolar). It is contemplated that the therapy source 24 is also a neural stimulation source 24a and includes a diagnostic mode in which the therapy source 24 generates neural stimulation having a biphasic waveform according to the present disclosure and a denervation mode in which the therapy source 24 generates RF energy to denervate the nerves of the associated blood vessels. It is contemplated that the therapy source 24 may be manually switched from the diagnostic mode to the denervation mode and vice versa, or may be automatically switched by an algorithm 44 stored on the memory 32 of the computing device. In at least one aspect of the present disclosure, electrode 58 communicates with independent neural stimulation source 24a to deliver neural stimulation to the vessel in question. A neural stimulation signal (e.g., a biphasic waveform) is generated by neural stimulation source 24a and transmitted to electrode 58, thereby causing stimulation of the sympathetic nerves as described herein.

[0076] In an embodiment, during the anodic phase of the biphasic pulse, neural stimulation is applied to the target tissue via a first electrode of electrodes 58 and received in a bipolar manner by a second electrode of electrodes 58, and during the cathodic phase of the biphasic pulse, neural stimulation is applied to the target tissue via a second electrode of electrodes 58 and received in a bipolar manner by the first electrode of electrodes 58. It is contemplated that during the anodic phase or the cathodic phase of the bipolar pulse, neural stimulation is applied by two or more of electrodes 58 or received by two or more of electrodes 58 in any suitable configuration, such as the proximal-most electrode 58 and the distal-most electrode 58, the proximal-most electrode 58 and the next proximal-most electrode 58, the proximal-most electrode 58 and an electrode 58 disposed immediately proximal to the distal-most electrode 58, etc.

[0077] In addition, one or more algorithms 44 can be used to stimulate multiple electrodes 58. For example, if there are four electrodes, there is an excitation order for the electrodes 58 to apply neural stimulation. In such examples, the electrodes 58 can be connected in a bipolar manner as follows. With a first anode phase between the first electrode and the fourth electrode, a first cathode phase between the fourth electrode and the first electrode. This can be followed by a second cathode phase between the fourth electrode and the first electrode, and a second anode phase between the first electrode and the fourth electrode. This can be followed by different pairs of electrodes 58 in a similar manner, such as between the first electrode and the third electrode 58, between the first electrode and the second electrode 58. A similar pattern can be followed between the second electrode and the fourth electrode and between the second electrode and the third electrode. Still in addition, the anode phase and the cathode phase do not need to be between the same pair of electrodes. For example, the first anode phase can be between the first electrode and the fourth electrode, and then the cathode phase between the fourth electrode and the second electrode. Alternatively, the first anode phase can be between the first electrode and the fourth electrode, and then the cathode phase between the fourth electrode and the first electrode 58, as in the first example, but the second anode phase can be between the second electrode and the fourth electrode, followed by the second cathode phase between the fourth electrode and the second electrode. The firing sequence of electrodes 58 is limited only by the number of electrodes 58 and the biphasic waveform.

[0078] During the application of neural stimulation to the target tissue, the leading phase of each consecutive pulse of the alternating biphasic waveform stimulates a greater number of nerves within the target tissue than conventional bipolar or monopolar stimulation. By stimulating a greater number of nerves within the target tissue, it is easier to identify the optimal placement of the electrode 58 for denervation within the target tissue to ensure effective renal denervation and optimal results. The position and / or orientation of the electrode 58 relative to the tissue wall can be changed between applying neural stimulation to map or otherwise identify the best nerve candidates for denervation. In this way, neural stimulation is applied to the target tissue via the electrode 58 in a first orientation, and physiological responses, such as increased blood pressure or increased vascular stiffness, are measured. As can be appreciated, stimulation of the nerves within the renal artery can result in a significant increase in blood pressure and / or increased vascular wall stiffness. The measurements of these physiological responses to neural stimulation can be compared to one or more thresholds, where a physiological response less than the one or more thresholds indicates that the stimulated nerve will not be a good candidate for denervation, and a physiological response greater than the one or more thresholds (e.g., greater blood pressure and / or greater vascular stiffness) indicates that the stimulated nerve will be a good candidate for denervation. If the physiological response is less than the threshold(s) (e.g. - lower blood pressure and / or greater vascular stiffness), the orientation of electrode 58 is changed by advancing or retracting treatment assembly 56 (e.g., proximally or distally) within the renal artery or rotating treatment assembly 56 in a clockwise or counterclockwise direction.

[0079] Once the orientation of the electrode 58 has been changed, neural stimulation is again applied to the target tissue and the physiological response is measured. Alternatively, the orientation of the electrode 58 can be changed multiple times between applying neural stimulation, and the orientation with the greatest physiological response can be identified and used to apply treatment or denervation energy. As can be appreciated, the above sequence can be repeated as many times as necessary to identify the optimal orientation and / or position of the electrode 58 relative to the target tissue or to identify the optimal nerve for denervation.

[0080] It is contemplated that the physiological response to the application of neural stimulation can be monitored by the control algorithm 44 stored on the computing device 20, wherein the location and results of the application of neural stimulation are stored in the memory 32. The stored physiological response can be compared with a predetermined threshold stored in the memory 32 or with other physiological responses stored in the memory to help the clinician identify the optimal location and / or orientation of the electrode 58 relative to the target tissue. A lookup table of data for the predetermined thresholds can be maintained in the memory 32 and accessed by the control algorithm 44 or other suitable application stored on the memory 32 during the procedure, and an alert can be presented on the user interface 28.

[0081] In addition to identifying candidates for denervation procedures, it is also contemplated that the biphasic neural stimulation waveforms described herein can be used to analyze the efficacy of denervation procedures. In this manner, after therapy is applied to the target tissue from the therapy source 24, neural stimulation can be applied via the electrode 58 to stimulate nerves within the target tissue and the physiological response to the neural stimulation can be measured. As can be appreciated, a successful denervation procedure will result in a reduced physiological response to the neural stimulation compared to the physiological response to the neural stimulation applied before denervation. Similar to the procedure described above with respect to identifying potential candidates for denervation, the physiological response to the neural stimulation applied via the electrode 58 can be measured and compared to one or more thresholds. In contrast to the above, a physiological response less than the one or more thresholds (e.g., lower blood pressure and / or lower vascular stiffness) indicates successful denervation, while a physiological response greater than the one or more thresholds (e.g., higher blood pressure and / or higher vascular stiffness) indicates that further denervation may be required. In embodiments where an increase in a physiological response (e.g., heart rate) compared to one or more thresholds is a desired physiological response to denervation, a measured physiological response greater than a predetermined threshold indicates successful denervation, while a physiological response less than a predetermined threshold indicates that further denervation may be required.

[0082] Thus far, the treatment device 50 has been described primarily in conjunction with a shape memory configuration, wherein exiting the guide catheter 62 or withdrawal of the guidewire 64 releases the shape memory alloy to achieve the desired helical shape of the treatment portion 56 of the treatment device 50. However, as described elsewhere, the present disclosure is not limited thereto. Figure 5 , the treatment device 150 may employ a balloon 152. As described above, during the navigation phase, the balloon 152 has a generally linear shape, and when in the desired position, the balloon 152 may be inflated to achieve the desired shape. The desired shape may be based on the side of the vessel or luminal tissue into which the treatment device 150 will be navigated and to which therapy will be applied. As is known in the art, a balloon may be employed to ensure contact of the RF electrode 154 and the ultrasound transducer 156 with the tissue. In addition, a balloon may be employed to center the microwave antenna 158 in the vessel.

[0083] It is contemplated that the balloon 152 may be multi-chambered or have one or more fluid ports, allowing, for example, different media to flow into the balloon 152 or into different chambers of the balloon 152. In one non-limiting embodiment, the balloon 152 may be filled with saline surrounding the microwave antenna 158, allowing good coupling (e.g., impedance matching) of the microwave energy emitted from the antenna to the tissue receiving the energy. The saline also works to supercool the tissue closest to the antenna (e.g., the wall of a blood vessel) to prevent necrosis of this tissue. The balloon 152 may also be used to limit the extent to which the cryogenic medium can act on the tissue, thereby limiting the diffusion of the cryogenic medium to only that area of ​​the balloon 152. In cryoablation and chemical ablation, the treatment device 150 may include one or more needles 160 that may be selectively extended (e.g., deployed) from the treatment device 150 and fluidly coupled to the therapy source 24, thereby supplying these therapies directly to the desired tissue. In this case, the balloon 152 provides a centered and stable platform for the needle 160 to leave the treatment device 150 and enter the tissue. In the present invention, balloon 152 may be an occlusive balloon, a non-occlusive balloon, or another configuration of a balloon that allows blood or other media to flow through the luminal tissue of the blood vessel.

[0084] It is contemplated that the treatment device 50, 150 may include multiple modalities for therapy, such that, for example, a single treatment device may include an RF electrode 154 and an ultrasound transducer 156, or an RF electrode 154 and a chemical ablation needle 160. Each of these is connected to a therapy source 24 that is configured to supply the indicated therapy type. Those skilled in the art will recognize that the treatment device 150 and therapy source 24 may provide any suitable combination of therapy capable of performing a denervation protocol.

[0085] Similar to Figure 3 and Figure 4 In an embodiment of the present invention, the treatment device 150 may include an RF electrode 154 disposed thereon for delivering therapy and / or neural stimulation to the tissue, as described above. In the case where, for example, the therapy modality is not RF ablation and therefore there is no electrode 154 on the balloon, the guide catheter 62 may include two or more electrodes 66 disposed thereon ( Figure 4 ) for delivering neural stimulation to the desired tissue. Electrode 66 of guide catheter 62 is used to deliver biphasic neural stimulation generated by neural stimulation source 24a to the target tissue and identify nerves that would be good candidates for denervation, as described in further detail above. With the candidate nerves identified and the location where treatment device 50 / 150 should be positioned identified, guide catheter 62 can be retracted (e.g., Figure 5 ) to expose the treatment portion 156 and balloon 152 to allow therapy to be applied via the RF electrode 154 (if employed), ultrasound transducer 156, microwave antenna 158 and / or needle 160.

[0086] Go to Figure 6 , a method of performing a treatment procedure is shown and generally identified by reference numeral 200. In step 202, the treatment device 50 is navigated to the target tissue. Once the treatment device is positioned adjacent to the target tissue, the treatment portion may optionally be transformed from a first state to a second, deployed state in step 204 such that one or more therapy delivery elements abut or otherwise contact the tissue. The neural stimulation electrode 66 is positioned within the guide catheter 62, guide wire 64, or other device such as a guide tube 64. Figure 4 In the case of another device depicted, step 204 may alternatively occur after step 208. In step 206, neural stimulation is applied to the vascular or luminal tissue to achieve stimulation of nerves within the tissue. In step 208, the physiological response to the application of neural stimulation to the vascular or luminal tissue is monitored and / or observed and compared to a predetermined threshold. If the physiological response to the neural stimulation is less than the predetermined threshold, the treatment device is repositioned relative to the vascular or luminal tissue in step 210, and thereafter, the method returns to step 206. If the physiological response to the neural stimulation is greater than the predetermined threshold, the therapy is applied to the vascular or luminal tissue in step 212. After the therapy is applied to the vascular or luminal tissue, further neural stimulation is applied to the vascular or luminal tissue in step 214, and the physiological response to the application of neural stimulation is monitored and / or observed and compared to the predetermined threshold in step 216. If the physiological response to the neural stimulation is greater than the threshold (indication of incomplete denervation), the method moves to step 218, where a check is performed to ensure that safety parameters are not exceeded. The safety parameter may be, for example, an assessment of the total duration of the procedure, the total energy delivered or removed from the tissue, or other parameters that, if exceeded, may undesirably damage tissue near the target tissue. If any of these have been exceeded, the method ends. If the safety parameter has not been exceeded at step 218, the method returns to step 212 for further application of therapy. In this way, therapy can be applied until successful denervation has been achieved. In step 216, if the physiological response to the neural stimulation is less than a threshold, it is determined in step 220 whether there are additional treatment locations to receive therapy. If not, the method ends, however, if there are still one or more treatment sites to receive therapy, the treatment device is moved to one of those locations in step 222, and the process returns to step 206 to apply neural stimulation to the target tissue at the new treatment site. The method continues until all tissue sites have received the desired therapy and evidence of successful denervation is shown.

[0087] Although generally described above, it is contemplated that the memory 32 may include any non-transitory computer-readable storage medium for storing data and / or software including instructions executable by the processor 30 and controlling the operation of the workstation 20 and, in some embodiments, the operation of the treatment device 50, the imaging device 70, and / or the ECG machine. In an embodiment, the 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 via a mass storage controller (not shown) and a communication bus (not shown).

[0088] Although the description of computer-readable media contained herein refers to solid-state storage devices, it should be understood 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 can include non-transitory, volatile and non-volatile, removable and non-removable media implemented in any method or technology for storing information such as computer-readable instructions, data structures, program modules or other data. For example, computer-readable storage media can include RAM, ROM, EPROM, EEPROM, flash memory or other solid-state memory technology, CD-ROM, DVD, Blu-ray or other optical storage devices, magnetic cassettes, magnetic tapes, magnetic disk storage devices or other magnetic storage devices, or any other media that can be used to store the desired information and can be accessed by the energy source 20.

[0089] Although several embodiments of the present disclosure have been shown in the accompanying drawings, it is not intended to limit the present disclosure thereto, as it is intended that the present disclosure be as broad as the art will allow and the specification should be read in the same manner. Therefore, the above description should not be interpreted as limiting, but merely as an illustration of the embodiments. Those skilled in the art will be able to envision other modifications within the scope and spirit of the claims appended hereto.

[0090] Further disclosed herein are the subject of the following clauses:

[0091] 1. A method of implementing and evaluating a treatment protocol, comprising:

[0092] navigating the therapeutic device to the target tissue;

[0093] transforming the treatment device from a first linear configuration to a second helical configuration such that a plurality of electrodes on the treatment device engage the target tissue;

[0094] applying pulses of neural stimulation energy having at least two phases to the target tissue via the plurality of electrodes, wherein each pulse of the neural stimulation energy comprises an anodic phase and a cathodic phase, and the phase of the neural stimulation energy is switched from anode to cathode or from cathode to anode for each consecutive pulse;

[0095] observing a physiological response to the pulse of stimulation energy to the nerve that exceeds a threshold and is indicative of a neural response;

[0096] denervating the nerves of the target tissue; and

[0097] Pulses of the nerve stimulation energy are applied to the target tissue, wherein a physiological response less than a threshold value indicates successful denervation of nerves of the target tissue.

[0098] 2. The method according to clause 1, wherein the physiological response is blood pressure or vascular stiffness.

[0099] 3. The method of clause 1, wherein the target tissue is one or more of a renal artery, a visceral artery, or a hepatic artery.

[0100] 4. The method of clause 1, wherein during the anodic phase, energy is applied to a first electrode of the plurality of electrodes and received by a second electrode of the plurality of electrodes.

[0101] 5. The method of clause 4, wherein during the cathodic phase, energy is applied to a second electrode of the plurality of electrodes and received by a first electrode of the plurality of electrodes.

[0102] 6. The method of clause 4, wherein during the anodic phase or the cathodic phase, energy is applied to or received by two or more electrodes of the plurality of electrodes.

[0103] 7. The method of clause 1, wherein the denervation is achieved by applying monopolar energy to the target tissue via the plurality of electrodes.

[0104] 8. The method of clause 1, wherein the denervation is achieved by a therapy modality selected from the group consisting of radiofrequency ablation, microwave ablation, ultrasound ablation, cryoablation, and chemical ablation.

[0105] 9. The method of clause 1, wherein the neural stimulation energy comprises a frequency between about 10 Hz and 30 Hz, a pulse width between about 2 ms and 10 ms, a voltage between about 5 V and 30 V, and a current between about 2 mA and 500 mA.

[0106] 10. The method of clause 1, wherein the neural stimulation energy is multi-phasic.

[0107] 11. The method of clause 10, wherein the neural stimulation energy is biphasic or triphasic.

[0108] 12. A method of assessing a target location for therapy, comprising:

[0109] applying a neural stimulation pulse to tissue at a target location, wherein the neural stimulation pulse comprises an anodic phase and a cathodic phase;

[0110] switching the phase of the neural stimulation pulse from anode to cathode or from cathode to anode for each successive pulse; and

[0111] Physiological responses to the neural stimulation pulses are observed, wherein responses exceeding a threshold value indicate a neural response indicating that the target location is a candidate for application of therapy.

[0112] 13. The method according to clause 12, wherein the physiological response is blood pressure or vascular stiffness.

[0113] 14. The method of clause 12, wherein the target location is one or more of a renal artery, a visceral artery, or a hepatic artery.

[0114] 15. The method of clause 12, wherein during the anodal phase, neural stimulation energy is applied to a first electrode of the plurality of electrodes and received by a second electrode of the plurality of electrodes.

[0115] 16. The method of clause 15, wherein during the cathodic phase, neural stimulation energy is applied to a second electrode of the plurality of electrodes and received by a first electrode of the plurality of electrodes.

[0116] 17. The method of clause 16, wherein during the anodic phase or the cathodic phase, neural stimulation energy is applied to or received by two or more electrodes of the plurality of electrodes.

[0117] 18. The method of clause 12, further comprising navigating a diagnostic device to the target location.

[0118] 19. The method of clause 18, further comprising transitioning the diagnostic device from a first configuration to a second configuration such that a plurality of electrodes on the diagnostic device engage tissue at the target location.

[0119] 20. The method of clause 19, wherein the diagnostic device is transformed from a linear configuration to a helical configuration to place the electrode into engagement with tissue at a target location.

[0120] 21. The method of clause 20, further comprising inflating the balloon to place the electrode into engagement with tissue at the target location.

[0121] 22. The method of clause 18, wherein the diagnostic device is a guide catheter or guidewire having a plurality of electrodes disposed thereon for delivering neural stimulation to the target tissue.

[0122] 23. The method of clause 22, further comprising placing at least two of a plurality of electrodes of a guide catheter or guidewire into engagement with tissue at the target location.

[0123] 24. The method of clause 12, further comprising applying a denervation therapy to the target tissue, the denervation therapy selected from the group consisting of radiofrequency ablation, microwave ablation, ultrasound ablation, cryoablation, and chemical ablation.

[0124] 25. The method of clause 12, wherein the neural stimulation energy is multi-phasic.

[0125] 26. The method of clause 25, wherein the neural stimulation energy is biphasic or triphasic.

[0126] 27. A system for performing diagnostic and therapeutic procedures, comprising:

[0127] a catheter comprising a plurality of electrodes and configured for placement proximate to target tissue; and

[0128] an energy source operably coupled to the conduit, the energy source having:

[0129] a diagnostic mode in which pulses of neural stimulation energy are generated for delivery between at least two electrodes of the plurality of electrodes in a bipolar manner, the pulsed neural stimulation energy comprising an anodic phase and a cathodic phase, and the energy source is configured to switch the phase of the pulsed neural stimulation energy from anode to cathode or from cathode to anode for each successive pulse; and

[0130] A denervation mode is provided in which monopolar radiofrequency energy is generated for delivery by the plurality of electrodes to denervate nerves of the target tissue.

[0131] 28. The system of clause 27, wherein the catheter has a first configuration and a second configuration, wherein in the second configuration the plurality of electrodes on the catheter engage tissue at the target tissue.

[0132] 29. The system of clause 28, wherein the first configuration is a linear configuration for navigating to the target tissue and the second configuration is a helical configuration for placing the plurality of electrodes into engagement with tissue at the target tissue.

[0133] 30. The system according to clause 28, further comprising a balloon disposed on the catheter, wherein

[0134] Inflation of the balloon places the plurality of electrodes into engagement with the target tissue.

[0135] 31. A system for performing diagnostic and therapeutic procedures, comprising:

[0136] a catheter comprising a plurality of electrodes and configured for placement proximate to a target tissue;

[0137] an energy source operably coupled to the catheter, the energy source generating pulses of neural stimulation energy for bipolar delivery between at least two electrodes of the plurality of electrodes, the pulsed neural stimulation energy comprising an anodic phase and a cathodic phase, and

[0138] The energy source is configured to switch the phase of the pulsed neural stimulation energy from anode to cathode or from cathode to anode for each successive pulse; and

[0139] A therapy source is coupled to the catheter for delivering denervation therapy to denervate nerves in the target tissue.

[0140] 32. The system of clause 31, wherein the therapy source is selected from the group consisting of:

[0141] A cryogenic source for delivering a cryogenic medium, an RF generator for generating monopolar radiofrequency energy, a microwave generator for generating microwave energy, and a chemical source for delivering a chemical medium.

[0142] 33. The system according to clause 31 further comprises a balloon disposed on the catheter, wherein

[0143] Inflation of the balloon places the plurality of electrodes into engagement with tissue at the target tissue.

[0144] 34. The system of clause 33, wherein the therapy source is a cryogenic source for delivering a cryoablative agent, wherein the balloon is filled with the cryoablative agent.

[0145] 35. A system according to clause 31, wherein the energy source is integrated with the therapy source.

[0146] 36. The system of clause 31, wherein the catheter comprises a second plurality of electrodes configured for placement proximate to the target tissue, the second plurality of electrodes coupled to the therapy source for delivering denervation therapy to the target tissue.

[0147] 37. The system of clause 31, wherein the energy source and the therapy source are each coupled to the plurality of electrodes so that the plurality of electrodes deliver neural stimulation to the tissue in the diagnostic mode.

[0148] Stimulate energy and deliver denervation therapy to the tissue in a denervation mode.

[0149] 38. The system of clause 31 , wherein the catheter has a first configuration and a second configuration, wherein in the second configuration the plurality of electrodes on the catheter engage tissue at the target tissue.

[0150] 39. The system of clause 38, wherein the first configuration is a linear configuration for navigating to the target tissue and the second configuration is a helical configuration for placing the plurality of electrodes into engagement with tissue at the target tissue.

[0151] 40. A system for performing diagnostic and therapeutic procedures, comprising:

[0152] a catheter comprising a plurality of electrodes and configured for placement proximate to target tissue; and

[0153] A workstation operably coupled to the catheter, the workstation comprising a memory and a processor, the memory storing instructions that when executed by the processor

[0154] When the processor:

[0155] applying pulses of neural stimulation energy having at least two phases to the target tissue via the plurality of electrodes, wherein each pulse of the neural stimulation energy comprises an anodic phase and a cathodic phase, and the phase of the neural stimulation energy is switched from anode to cathode or from cathode to anode for each consecutive pulse;

[0156] observing a physiological response to the pulse of stimulation energy to the nerve that exceeds a threshold and is indicative of a neural response;

[0157] denervating the nerves of the target tissue; and

[0158] Pulses of the nerve stimulation energy are applied to the target tissue, wherein a physiological response less than a threshold value indicates successful denervation of nerves of the target tissue.

[0159] 41. The system of clause 40, further comprising an energy source operably coupled to the catheter, the energy source configured to generate a therapy modality selected from the group consisting of radiofrequency ablation, microwave ablation, ultrasonic ablation, cryoablation, and chemical ablation.

[0160] 42. The system of clause 41, wherein the energy source is configured to generate the neural stimulation energy when in a diagnostic mode and to generate a therapy modality when in a denervation mode.

[0161] 43. The system of clause 40, wherein the neural stimulation energy comprises a frequency between about 10 Hz and 30 Hz, a pulse width between about 2 ms and 10 ms, a voltage between about 5 V and 30 V, and a current between about 2 mA and 500 mA.

[0162] 44. The system according to clause 40, further comprising a balloon disposed on the catheter, wherein

[0163] Inflation of the balloon places the plurality of electrodes into engagement with the target tissue.

Claims

1. A system for performing diagnostic and therapeutic procedures, comprising: a catheter comprising a plurality of electrodes and configured for placement proximate to a target tissue; and an energy source operably coupled to the conduit, the energy source having: a diagnostic mode wherein pulses of neural stimulation energy are generated for delivery between at least two electrodes of the plurality of electrodes in a bipolar manner, the pulsed neural stimulation energy comprising an anodic phase and a cathodic phase, and the energy source is configured to switch the phase of the pulsed neural stimulation energy from anode to cathode or from cathode to anode for each consecutive pulse; and A denervation mode is provided in which monopolar radiofrequency energy is generated for delivery by the plurality of electrodes to denervate nerves of the target tissue. 2 . The system of claim 1 , wherein the catheter has a first configuration and a second configuration, wherein in the second configuration the plurality of electrodes on the catheter engage tissue at the target tissue.

3. The system of claim 2, wherein the first configuration is a linear configuration for navigating to the target tissue and the second configuration is a helical configuration for placing the plurality of electrodes into engagement with tissue at the target tissue.

4. The system of claim 2, further comprising a balloon disposed on the catheter, wherein inflation of the balloon places the plurality of electrodes into engagement with the target tissue.

5. A system for performing diagnostic and therapeutic procedures, comprising: a catheter comprising a plurality of electrodes and configured for placement proximate to a target tissue; an energy source operably coupled to the catheter, the energy source generating pulses of neural stimulation energy for delivery between at least two electrodes of the plurality of electrodes in a bipolar manner, the pulsed neural stimulation energy comprising an anodic phase and a cathodic phase, and the energy source being configured to switch the phase of the pulsed neural stimulation energy from anode to cathode or from cathode to anode for each consecutive pulse; and A therapy source is coupled to the catheter for delivering denervation therapy to denervate nerves of the target tissue.

6. The system of claim 5, wherein the therapy source is selected from the group consisting of: a cryogenic source for delivering a cryogenic medium, an RF generator for generating monopolar radiofrequency energy, a microwave generator for generating microwave energy, and a chemical source for delivering a chemical medium.

7. The system of claim 5, further comprising a balloon disposed on the catheter, wherein inflation of the balloon places the plurality of electrodes into engagement with tissue at the target tissue.

8. The system of claim 7, wherein the therapy source is a cryogenic source for delivering a cryoablative agent, wherein the balloon is filled with the cryoablative agent.

9. The system of claim 5, wherein the energy source is integrated with the therapy source.

10. The system of claim 5, wherein the catheter comprises a second plurality of electrodes configured for placement proximate to a target tissue, the second plurality of electrodes coupled to the therapy source for delivering denervation therapy to the target tissue.

11. The system of claim 5, wherein the energy source and the therapy source are each coupled to the plurality of electrodes such that the plurality of electrodes deliver neural stimulation energy to the tissue in a diagnostic mode and deliver denervation therapy to the tissue in a denervation mode.

12. The system of claim 5, wherein the catheter has a first configuration and a second configuration, wherein in the second configuration the plurality of electrodes on the catheter engage tissue at the target tissue.

13. The system of claim 12, wherein the first configuration is a linear configuration for navigating to the target tissue and the second configuration is a helical configuration for placing the plurality of electrodes into engagement with tissue at the target tissue.

14. A system for performing diagnostic and therapeutic procedures, comprising: a catheter comprising a plurality of electrodes and configured for placement proximate to a target tissue; and A workstation operably coupled to the catheter, the workstation comprising a memory and a processor, the memory storing instructions that, when executed by the processor, cause the processor to: applying pulses of neural stimulation energy having at least two phases to the target tissue via the plurality of electrodes, wherein each pulse of the neural stimulation energy comprises an anodic phase and a cathodic phase, and switching the phase of the neural stimulation energy from anode to cathode or from cathode to anode for each consecutive pulse; observing a physiological response to the pulse of neural stimulation energy that exceeds a threshold and is indicative of a neural response; denervating the nerve of the target tissue; as well as Pulses of the nerve stimulation energy are applied to the target tissue, wherein a physiological response less than a threshold value indicates successful denervation of the nerve of the target tissue.

15. The system of claim 14, further comprising an energy source operably coupled to the catheter, the energy source configured to generate a therapy modality selected from the group consisting of radiofrequency ablation, microwave ablation, ultrasonic ablation, cryoablation, and chemical ablation.

16. The system of claim 15, wherein the energy source is configured to generate the neural stimulation energy when in a diagnostic mode and to generate a therapy modality when in a denervation mode.

17. The system of claim 14, wherein the neural stimulation energy comprises a frequency between about 10 Hz and 30 Hz, a pulse width between about 2 ms and 10 ms, a voltage between about 5 V and 30 V, and a current between about 2 mA and 500 mA.

18. The system of claim 14, further comprising a balloon disposed on the catheter, wherein inflation of the balloon places the plurality of electrodes into engagement with the target tissue.

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