System for applying energy and denervating a pulmonary artery - Patent application

Abstract

A catheter system for ablation of tissue surrounding a blood vessel, e.g., a pulmonary artery, to reduce neural activity of the nerves surrounding the blood vessel. The catheter system includes an elongated shaft having a proximal portion and a distal portion coupled to a handle. The distal portion includes a transducer and an expandable anchor that can be actuated to transition between a collapsed delivery state and an expanded deployed state, the anchor centering the transducer within the blood vessel. The transducer can be actuated to emit energy to reduce neural activity of the nerves surrounding the blood vessel. Systems and methods for verifying that neural activity of the nerves surrounding the blood vessel has been sufficiently reduced are further provided.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to European Patent Application No. 21305873.8, filed June 24, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure is generally directed to medical devices, systems, and methods for applying energy and reducing neural activity in blood vessels, such as the pulmonary artery, to treat pulmonary hypertension and / or other pulmonary vascular disorders. [Background technology]

[0003] Pulmonary hypertension is a disease phenomenon of multifactorial etiology with high morbidity and mortality. Increased disease causes affect the right side of the heart, ultimately resulting in hypertrophy and dysfunction of the left side as well as the right side of the heart in many cases. The prognosis of pulmonary hypertension has historically been poor, with median survival rates historically less than three years. Currently, with the advent of new pharmacological therapies, survival rates have improved to 50-60% at five years. However, many patients continue to progress to worsening stages of pulmonary hypertension, and despite improvements in therapy, the prognosis for the condition remains alarming.

[0004] In light of the aforementioned shortcomings of previously known systems and methods, there is a need for improved systems and methods for treating pulmonary hypertension, particularly minimally invasive treatments that reduce or eliminate the need for pharmaceutical remedies and / or that may be permanent or at least long-lasting.

[0005] Treatment of pulmonary hypertension via endovascular denervation of the pulmonary artery was first described in U.S. Patent No. 9,005,100 to Gnanashanmugam, the entire contents of which are incorporated herein by reference. Additionally, it would be desirable to provide a system for denervating blood vessels, such as the pulmonary artery, as well as a system for verifying that denervation has been completed. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Patent No. 9,005,100 Summary of the Invention [Means for solving the problem]

[0007] The present disclosure overcomes the shortcomings of previously known systems and methods for reducing pulmonary hypertension by providing a system and method for blocking nerves (e.g., sympathetic nerves) surrounding and / or innervating the left, right, and / or main pulmonary arteries. Neuromodulation may be accomplished via ablation, denervation, which may or may not be reversible, stimulation, etc. For example, the systems disclosed herein are configured to navigate a catheter from a remote insertion point through the heart and into the pulmonary branch arteries and trunk. The catheter may include an anchor that, when deployed, will anchor and center the transducer within the vessel wall at the target ablation site. Once the nerves located at the ablation site have been ablated, the anchor may be collapsed and the transducer may be repositioned to another ablation site within the vessel. This method of deployment, ablation, collapse, and movement may be repeated until both the pulmonary branch artery and the pulmonary trunk are ablated.

[0008] According to one aspect of the disclosure, a system for reducing neural activity of nerves surrounding a patient's blood vessel is provided. The system may include a handle, an inner catheter, a transducer assembly, an outer catheter, an expandable anchor, and a sheath. For example, the inner catheter may include a guidewire lumen extending through at least a portion of the length of the inner catheter and a proximal region of the inner catheter operably coupled to the handle. The transducer assembly may include a transducer shaft having an ultrasound transducer coupled thereto. The ultrasound transducer may be actuated to emit ultrasound energy within the blood vessel and reduce neural activity of nerves surrounding the blood vessel. The transducer shaft may include a lumen sized and shaped to slidably receive the inner catheter therein and a proximal region operably coupled to the handle. The outer catheter may include a lumen sized and shaped to receive the transducer shaft therein and a proximal region operably coupled to the handle. The expandable anchor may include a distal end coupled to the inner catheter and a proximal end coupled to the outer catheter, such that relative movement between the inner and outer catheters transitions the expandable anchor between a collapsed delivery state and an expanded deployed state. Additionally, the expandable anchor may have an ultrasound transducer centrally located within a patient's blood vessel in the expanded deployed state. The sheath may include a lumen sized and shaped to slidably receive therein the outer catheter and the expandable anchor in the collapsed delivery state. The distal region of the sheath may have sufficient stiffness to facilitate transition of the expandable anchor from the expanded deployed state to the collapsed delivery state in response to movement of the distal region of the sheath relative to the expandable anchor without buckling the distal region of the sheath, and the proximal region of the sheath is operably coupled to the handle. The blood vessel may be a pulmonary artery, and the ultrasound transducer may be activated to emit ultrasound energy within the pulmonary artery to reduce neural activity of nerves surrounding the pulmonary artery and treat pulmonary hypertension.

[0009] The system may further include a separation sleeve having a lumen sized and shaped to slidably receive the sheath therein, with a proximal region of the separation sleeve fixedly coupled to the handle. In addition, the system may include an introducer having a lumen sized and shaped to slidably receive the sheath and separation sleeve therein. For example, the introducer may be fixed relative to the patient and actuated to prevent relative movement between the separation sleeve and the introducer, such that the sheath is movable relative to the separation sleeve without relative movement between the transducer assembly and the patient. Additionally, the introducer may include a valve disposed within the introducer lumen, such that the introducer may be actuated to prevent relative movement between the separation sleeve and the introducer by actuating the valve relative to the separation sleeve once the separation sleeve is disposed within the introducer lumen.

[0010] The distal end of the inner catheter may include an atraumatic tip. For example, the atraumatic tip may include a tapered profile such that the cross-sectional area of ​​the atraumatic tip decreases from the proximal end of the atraumatic tip to the distal end of the atraumatic tip. In the delivery configuration, the distal end of the sheath abuts the atraumatic tip. Additionally, the distal end of the expandable anchor may be coupled to the inner catheter via a ring slidably disposed on the inner catheter such that the distal end of the expandable anchor is slidably coupled to the inner catheter. The outer catheter may be fixedly coupled to the handle, and the inner catheter may be actuated to move relative to the outer catheter and transition the expandable anchor between the collapsed delivery state and the expanded deployed state. Alternatively, the inner catheter may be fixedly coupled to the handle, and the outer catheter may be actuated to move relative to the inner catheter and transition the expandable anchor between the collapsed delivery state and the expanded deployed state.

[0011] The expandable anchor may include a plurality of struts, for example a plurality of diamond-shaped struts. The expandable anchor may be formed from a shape memory material. Furthermore, the expandable anchor may have a radial force in an expanded deployed state that exceeds the stiffness force of the inner catheter, the transducer shaft, the outer catheter, and the distal region of the sheath. In addition, the stiffness of the distal region of the sheath may exceed the stiffness of the proximal region of the sheath. The outer diameter of the distal region of the sheath may be greater than the outer diameter of the proximal region of the sheath. The transducer shaft and the outer catheter may be sealed to create a fluidically sealed cavity therebetween, and thus at least one cable may be disposed within the fluidically sealed cavity to provide electrical energy to the ultrasound transducer for emitting ultrasound energy.

[0012] The system may further include a generator operably coupled to the ultrasound transducer. The generator may be actuated to provide electrical energy to the ultrasound transducer and cause the ultrasound transducer to emit ultrasonic energy. In addition, the system may include a sensor that may measure a temperature of the ultrasound transducer, and the generator may include a control loop that is programmed to adapt the electrical energy provided to the ultrasound transducer if the temperature of the ultrasound transducer exceeds a predetermined threshold. In addition, the transducer may convert acoustic energy reflected from adjacent anatomical airway structures into electrical energy, and the generator may include a control loop that is programmed to stop emitting ultrasonic energy if the electrical energy exceeds a predetermined threshold, the electrical energy being indicative of the level of acoustic energy reflected from adjacent anatomical airway structures.

[0013] The system may further include one or more pacing electrodes disposed on the expandable anchor. The one or more pacing electrodes may be actuated to pace the vessel and elicit a physiological response from the patient when the phrenic nerve is located around the vessel. Additionally, the system may include an expansion mechanism that may apply a sufficient force to the inner wall of the vessel to expand the vessel and stimulate baroreceptors within the vessel. The expansion mechanism may include an expandable member that may be expanded from a collapsed state to an expanded state, the expandable member applying a force to the inner wall of the vessel. Alternatively, the expansion mechanism may include a torque applying mechanism that may be actuated to bend the extension shaft of the system within the vessel and apply a force to the inner wall of the vessel.

[0014] Additionally, the system may further include a controller operably coupled to the one or more sensors capable of measuring pressure within the blood vessel. The controller may be programmed to receive a first pressure information within the blood vessel from the one or more sensors at a first time, receive a second pressure information within the blood vessel from the one or more sensors at a second time while the expandable member applies a first force to the inner wall and opens the blood vessel, receive a third pressure information within the blood vessel from the one or more sensors at a third time while the expandable member applies a second force to the inner wall and opens the blood vessel after ultrasonic energy is released within the blood vessel via the ultrasonic transducer to reduce neural activity of nerves surrounding the blood vessel, compare the second pressure information to the third pressure information, and determine whether the ultrasonic energy has reduced neural activity of nerves surrounding the blood vessel.

[0015] For example, the second pressure information may indicate a first pressure gradient between the pressure in the vessel while the first force is applied to the inner wall to open the vessel and a pre-opening pressure in the vessel associated with the first pressure information, and the third pressure information may indicate a second pressure gradient between the pressure in the vessel while the second force is applied to the inner wall to open the vessel and a pre-opening pressure in the vessel associated with the first pressure information. Thus, the ultrasound energy may be reducing neural activity of nerves around the vessel if a comparison of the second and third pressure information indicates that the second pressure gradient is above a predetermined threshold and less than the first pressure gradient. The system may further include one or more sensors that may measure pressure in the vessel.

[0016] The system may further include a transducer catheter having a lumen sized and shaped to receive the transducer shaft therein and a proximal region operably coupled to the handle such that the transducer catheter is slidably disposed within the outer catheter. In this configuration, the transducer shaft and the transducer catheter are sealed to create a fluidically sealed cavity therebetween, and thus at least one cable may be disposed within the fluidically sealed cavity to provide electrical energy to the ultrasound transducer for emitting ultrasonic energy.

[0017] The handle may be actuated to cause translation of the ultrasound transducer relative to the inner and outer catheters via the transducer shaft and the transducer catheter. At least one of the inner catheter, the outer catheter, and the sheath may include a guidewire port sized and shaped to receive a guidewire therethrough. The system may further include one or more intravascular ultrasound (IVUS) transducers disposed on at least one of the inner catheter distal to the ultrasound transducer, the outer catheter between the ultrasound transducer and the proximal end of the expandable anchor, or the outer catheter proximal to the proximal end of the expandable anchor. The one or more IVUS transducers may generate data for detecting anatomical structures adjacent to the blood vessel within the field of view of the one or more IVUS transducers. The one or more IVUS transducers may include a shield for masking at least a portion of the ultrasound energy emitted from the one or more IVUS transducers.

[0018] In addition, the system may include a torque shaft having a lumen sized and shaped to receive the inner catheter therein and a proximal region operably coupled to the handle. The torque shaft may be coupled to the ultrasound transducer and may be actuated to cause rotation of the ultrasound transducer relative to the inner catheter. The ultrasound transducer may include multiple transducer segments, each of which may be independently actuable to selectively emit ultrasound energy.

[0019] According to another aspect of the present disclosure, a method is provided for reducing neural activity of nerves surrounding a blood vessel of a patient, the method may include selecting a catheter system including a handle, an inner catheter having a guidewire lumen, a transducer assembly slidably disposed over the inner catheter, an outer catheter disposed over a transducer shaft of the transducer assembly, an expandable anchor having a distal end coupled to the inner catheter and a proximal end coupled to the outer catheter, and a sheath slidably disposed over the outer catheter. The method further includes the steps of advancing the distal end of the guidewire to a target location within the blood vessel; advancing the catheter system through the guidewire lumen and over the proximal end of the guidewire until an ultrasound transducer of a transducer assembly is at the target location within the blood vessel and an expandable anchor is disposed within a sheath in a collapsed delivery state; retracting the sheath to expose the expandable anchor within the blood vessel; and moving the inner catheter and the outer catheter relative to each other to transition the expandable anchor from the collapsed delivery state to an expanded deployed state, the expandable anchor in the expanded deployed state centering the ultrasound transducer within the blood vessel. The method may include: activating the ultrasonic transducer to emit ultrasonic energy within the blood vessel to reduce neural activity of nerves surrounding the blood vessel; moving the inner catheter and the outer catheter relative to one another to transition the expandable anchor from the expanded deployed state to a collapsed delivery state; advancing a sheath over the expandable anchor in the collapsed delivery state, wherein a distal region of the sheath has sufficient stiffness to facilitate transition of the expandable anchor from the expanded deployed state to the collapsed delivery state in response to movement of the distal region of the sheath relative to the expandable anchor without buckling the distal region of the sheath; and removing the catheter system from the patient.

[0020] Advancing the catheter system through the guidewire lumen and over the proximal end of the guidewire until the ultrasound transducer is at the target location within the blood vessel may include advancing the catheter system through the guidewire lumen and over the proximal end of the guidewire until the ultrasound transducer is at the target location within the pulmonary artery. The method may further include inserting an introducer into the patient's vasculature such that the introducer is fixed relative to the patient, such that advancing the catheter system over the proximal end of the guidewire includes advancing the catheter system over the proximal end of the guidewire and through the introducer.

[0021] Additionally, the method may include actuating a valve disposed within a lumen of the introducer relative to the separation sleeve of the catheter system to prevent relative movement between the separation sleeve and the introducer such that the sheath is movable relative to the separation sleeve without relative movement between the transducer assembly and the patient. Thus, the separation sleeve may be slidably disposed over at least a portion of the sheath and fixedly coupled to the handle. The method may further include translating the ultrasound transducer relative to the expandable anchor in an expanded deployed state within the vessel.

[0022] Additionally, the method may include, prior to removing the catheter system from the patient, advancing the catheter system until the ultrasonic transducer is at a second target location in another portion of the blood vessel, retracting the sheath to expose the expandable anchor in the other portion of the blood vessel, moving the inner catheter and the outer catheter relative to each other to transition the expandable anchor from a collapsed delivery state to an expanded deployed state in the other portion of the blood vessel, and activating the ultrasonic transducer to emit ultrasonic energy in the other portion of the blood vessel and reduce neural activity of nerves surrounding the other portion of the blood vessel. Activating the ultrasonic transducer to emit ultrasonic energy in the blood vessel may include activating the ultrasonic transducer according to a predetermined activation regimen. The predetermined activation regimen may include predetermined non-ablative periods between predetermined ablative periods.

[0023] Further, the method may include pacing the vessel via one or more pacing electrodes disposed on the expandable anchor in an expanded deployed state prior to activating the ultrasonic transducer to emit ultrasonic energy within the vessel when the phrenic nerve is located around the vessel, eliciting an observable physiological response from the patient, and not activating the ultrasonic transducer to emit ultrasonic energy at a target location within the vessel when the physiological response is observed, to avoid damaging the phrenic nerve. Additionally or alternatively, the method may include pacing the vessel via one or more pacing electrodes disposed on the expandable anchor in an expanded deployed state while the ultrasonic energy is being emitted within the vessel, to elicit an observable physiological response from the patient when the phrenic nerve is located around the vessel, and ceasing the emission of ultrasonic energy within the vessel when a change in the physiological response observed over time exceeds a predetermined threshold to avoid damaging the phrenic nerve.

[0024] According to another aspect of the present invention, another method for reducing neural activity of nerves surrounding a blood vessel of a patient is provided, which may include measuring first pressure information within the blood vessel, applying a first force to an inner wall of the blood vessel to open the blood vessel, measuring second pressure information within the blood vessel while the first force is applied to the inner wall to open the blood vessel, releasing energy via an ablation device positioned within the blood vessel to ablate nerves surrounding the blood vessel, applying the second force to the inner wall of the blood vessel to open the blood vessel, measuring third pressure information within the blood vessel while the second force is applied to the inner wall to open the blood vessel, and comparing the second pressure information to the third pressure information to determine whether the released energy reduces neural activity of nerves surrounding the blood vessel.

[0025] The second pressure information may indicate a first pressure gradient between the pressure in the vessel while the first force is applied to the inner wall to open the vessel and a pre-opening pressure in the vessel associated with the first pressure information, and the third pressure information may indicate a second pressure gradient between the pressure in the vessel while the second force is applied to the inner wall to open the vessel and a pre-opening pressure in the vessel associated with the first pressure information. The released energy may have reduced neural activity of nerves around the vessel if a comparison of the second and third pressure information indicates that the second pressure gradient is above a predetermined threshold and less than the first pressure gradient. Additionally or alternatively, the released energy may have reduced neural activity of nerves around the vessel if the second pressure gradient is zero.

[0026] Applying the first and second forces to the inner wall of the blood vessel to open the blood vessel may include applying a force sufficient to stimulate baroreceptors in the blood vessel. Additionally, applying at least one of the first or second forces to the inner wall of the blood vessel to open the blood vessel may include expanding an expandable member from a collapsed state to an expanded state, the expandable member being disposed on a catheter sized and shaped to be positioned within the blood vessel. In the expanded state, the expandable device may not completely occlude blood through the blood vessel. The ablation device may be disposed on the same catheter as the expandable member. Alternatively, the ablation device may be disposed on a second catheter sized and shaped to be positioned within the vessel, and thus the second catheter is different from the catheter. Alternatively, applying at least one of the first or second forces to the inner wall of the blood vessel to open the blood vessel may include applying a torque to the catheter shaft to bend the catheter shaft within the blood vessel and apply a force.

[0027] If the emitted energy does not reduce the neural activity of the nerves around the blood vessel based on the comparison of the second and third pressure information, the method further includes emitting energy via an ablation device positioned within the blood vessel to ablate the nerves around the blood vessel, applying a third force to an inner wall of the blood vessel to open the blood vessel, measuring a fourth pressure information within the blood vessel while the third force is applied to the inner wall to open the blood vessel, and comparing the fourth pressure information to at least one of the second or third pressure information to determine whether the emitted energy reduces the neural activity of the nerves around the blood vessel. Furthermore, emitting energy via an ablation device positioned within the blood vessel to ablate the nerves around the blood vessel may include emitting at least one of focused ultrasound, unfocused ultrasound, radio frequency, microwave, cryoenergy, laser, or pulsed field electroporation. The method may further include deploying an expandable anchor within the vessel to centrally position the ablation device within the vessel.

[0028] According to another aspect of the present disclosure, another system for reducing neural activity of nerves surrounding a patient's blood vessel is provided. The system may include a catheter assembly, an expansion mechanism, one or more sensors capable of measuring pressure within the blood vessel, and a controller operably coupled to the one or more sensors. The catheter assembly may have a proximal region operably coupled to a handle and a distal region sized and shaped to be positioned within the blood vessel, and the distal region of the catheter assembly may include an ablation device that may be activated to release energy within the blood vessel and reduce neural activity of nerves surrounding the blood vessel. The expansion mechanism may be activated to apply sufficient force to an inner wall of the blood vessel to expand the blood vessel and stimulate baroreceptors within the blood vessel.

[0029] The controller may be programmed to receive first pressure information within the blood vessel from the one or more sensors at a first time, receive second pressure information within the blood vessel from the one or more sensors at a second time while the expansion mechanism applies a first force to the inner wall and expands the blood vessel, receive third pressure information within the blood vessel from the one or more sensors at a third time while the expansion mechanism applies a second force to the inner wall and expands the blood vessel after ultrasonic energy is released within the blood vessel via the ultrasonic transducer to reduce neural activity of nerves surrounding the blood vessel, and compare the second pressure information to the third pressure information to determine whether the ultrasonic energy has reduced neural activity of nerves surrounding the blood vessel.

[0030] The expansion mechanism may include an expandable member that can be expanded from a collapsed state to an expanded state to apply a force to the inner wall of the blood vessel. Alternatively, the expansion mechanism may include a torque mechanism configured to bend the shaft of the catheter assembly within the blood vessel and apply a force to the inner wall of the blood vessel. The system may further include an expandable anchor that can transition between a collapsed delivery state and an expanded deployed state, the expandable anchor centering the ablation device within the blood vessel. Additionally, the ablation device may emit at least one of focused ultrasound, unfocused ultrasound, radio frequency, microwave, cryoenergy, laser, or pulsed field electroporation.

[0031] According to another aspect of the present disclosure, a system for reducing neural activity of nerves surrounding a pulmonary artery of a patient is provided. The system may include a handle, an elongated shaft, an ultrasound transducer, and an expandable anchor. The elongated shaft may have a proximal region and a distal region operably coupled to the handle. The ultrasound transducer may be disposed on the distal region of the elongated shaft and may be activated to emit ultrasound energy within the pulmonary artery to reduce neural activity of nerves surrounding the pulmonary artery. The expandable anchor may be disposed on the distal region of the elongated shaft and may transition between a collapsed delivery state and an expanded deployed state, the expandable anchor causing the ultrasound transducer to be centrally located within the pulmonary artery of the patient.

[0032] The expandable anchor may include a plurality of struts having rounded edges configured to prevent damage to the pulmonary artery. The system may further include a sheath having a lumen sized and shaped to slidably receive therein the elongate shaft and the expandable anchor in a collapsed delivery state. The distal region of the sheath may have sufficient stiffness to facilitate transition of the expandable anchor from the expanded deployed state to the collapsed delivery state in response to movement of the distal region of the sheath relative to the expandable anchor without buckling the distal region of the sheath, and the proximal region of the sheath is operably coupled to the handle. The ultrasonic transducer may emit ultrasonic energy within the main branch of the pulmonary artery, the right branch of the pulmonary artery, or the left branch of the pulmonary artery, or any combination thereof. [Brief description of the drawings]

[0033] [Figure 1A] FIG. 1A is a perspective view of an exemplary catheter system for treating tissue constructed in accordance with the principles of the present disclosure.

[0034] [Figure 1B] FIG. 1B is a schematic cross-sectional view of the catheter system of FIG. 1A.

[0035] [Figure 2A] FIG. 2A illustrates the distal region of the catheter system of FIG. 1A.

[0036] [Figure 2B] FIG. 2B illustrates an exemplary expandable anchor constructed in accordance with the principles of the present disclosure.

[0037] [Figure 2C] FIG. 2C illustrates an exemplary sheath constructed in accordance with the principles of the present disclosure.

[0038] [Diagram 3] FIG. 3 is a perspective view of an exemplary handle of the catheter system of FIG. 1A constructed in accordance with the principles of the present disclosure.

[0039] [Figure 4A] FIG. 4A is a cross-sectional view of the catheter system of FIG. 1A, and FIGS. 4B-4E are enlarged views of the handle of FIG. 4A. [Figure 4B] FIG. 4A is a cross-sectional view of the catheter system of FIG. 1A, and FIGS. 4B-4E are enlarged views of the handle of FIG. 4A. [Figure 4C] FIG. 4A is a cross-sectional view of the catheter system of FIG. 1A, and FIGS. 4B-4E are enlarged views of the handle of FIG. 4A. [Figure 4D] FIG. 4A is a cross-sectional view of the catheter system of FIG. 1A, and FIGS. 4B-4E are enlarged views of the handle of FIG. 4A. [Figure 4E] FIG. 4A is a cross-sectional view of the catheter system of FIG. 1A, and FIGS. 4B-4E are enlarged views of the handle of FIG. 4A.

[0040] [Figure 5A] FIG. 5A illustrates the catheter system of FIG. 1A in a delivery configuration.

[0041] [Figure 5B] FIG. 5B illustrates the catheter system of FIG. 1A in a deployed configuration.

[0042] [Figure 6A] 6A-6D are various views of an exemplary transducer assembly constructed in accordance with the principles of the present disclosure. [Figure 6B] 6A-6D are various views of an exemplary transducer assembly constructed in accordance with the principles of the present disclosure. [Figure 6C] 6A-6D are various views of an exemplary transducer assembly constructed in accordance with the principles of the present disclosure. [Figure 6D] 6A-6D are various views of an exemplary transducer assembly constructed in accordance with the principles of the present disclosure.

[0043] [Figure 7] FIG. 7 is a flow chart of an exemplary method for treating tissue in accordance with the principles of the present disclosure.

[0044] [Figure 8] FIG. 8 is a schematic diagram illustrating the positioning of the catheter system of FIG. 1A within a patient, in accordance with the principles of the present disclosure.

[0045] [Figure 9] FIG. 9 is a flow chart of an exemplary method for confirming a reduction in neural activity of a nerve in accordance with the principles of the present disclosure.

[0046] [Figure 10] FIG. 10 is a distribution plot illustrating energy emission intensity.

[0047] [Figure 11] FIG. 11 illustrates a distal region of an alternative exemplary catheter system having a guidewire port constructed in accordance with the principles of the present disclosure.

[0048] [Figure 12] FIG. 12 is a cross-sectional view of an alternative exemplary handle constructed in accordance with the principles of the present disclosure.

[0049] [Figure 13] FIG. 13 is a graph illustrating the control loop of the catheter system.

[0050] [Figure 14] FIG. 14 is a distribution plot illustrating the direct targeting of energy emission in accordance with the principles of the present disclosure.

[0051] [Figure 15] FIG. 15 illustrates an alternative exemplary catheter system having a rotatable torque shaft constructed in accordance with the principles of the present disclosure.

[0052] [Figure 16] FIG. 16 illustrates an alternative exemplary catheter system having an imaging transducer in accordance with the principles of the present disclosure.

[0053] [Figure 17A] FIG. 17A illustrates an alternative exemplary imaging transducer having a shield constructed in accordance with the principles of the present disclosure.

[0054] [Figure 17B] FIG. 17B illustrates the energy emission of the imaging transducer of FIG. 17A within a patient.

[0055] [Figure 18] FIG. 18 illustrates an alternative exemplary catheter system having pacing electrodes in accordance with the principles of the present disclosure.

[0056] [Figure 19A] FIG. 19A illustrates an exemplary transducer constructed in accordance with the principles of the present disclosure.

[0057] [Figure 19B] FIG. 19B illustrates another exemplary transducer constructed in accordance with the principles of the present disclosure.

[0058] [Figure 19C] FIG. 19C illustrates another exemplary transducer constructed in accordance with the principles of the present disclosure.

[0059] [Figure 19D] FIG. 19D illustrates an example transducer connection implementation.

[0060] [Figure 19E] FIG. 19E illustrates another exemplary transducer constructed in accordance with the principles of the present disclosure.

[0061] [Figure 20A] 20A-20D illustrate various exterior shapes of example transducers. [Figure 20B] 20A-20D illustrate various exterior shapes of example transducers. [Figure 20C] 20A-20D illustrate various exterior shapes of example transducers. [Figure 20D] 20A-20D illustrate various exterior shapes of example transducers.

[0062] [Figure 21A] FIG. 21A illustrates an exemplary lens constructed in accordance with the principles of the present disclosure.

[0063] [Figure 21B] FIG. 21B diagrammatically illustrates energy rays emanating from the lens of FIG. 21A for longitudinally focusing and concentrating energy.

[0064] [Figure 21C] FIG. 21C illustrates some of the energy application geometries.

[0065] [Figure 21D] FIG. 21D illustrates an exemplary transducer assembly constructed in accordance with the principles of the present disclosure.

[0066] [Figure 22A] FIG. 22A illustrates an exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0067] [Figure 22B] FIG. 22B illustrates the anchor of FIG. 22A in a deployed state.

[0068] [Figure 22C] FIG. 22C illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0069] [Figure 22D] FIG. 22D illustrates the anchor of FIG. 22C in a deployed state.

[0070] [Figure 23A] 23A and 23B illustrate an exemplary transducer assembly constructed in accordance with the principles of the present disclosure. [Figure 23B] 23A and 23B illustrate an exemplary transducer assembly constructed in accordance with the principles of the present disclosure.

[0071] [Figure 23C] 23C-23E illustrate an exemplary method of rotating the anchor between ablations. [Figure 23D] 23C-23E illustrate an exemplary method of rotating the anchor between ablations. [Figure 23E] 23C-23E illustrate an exemplary method of rotating the anchor between ablations.

[0072] [Figure 24A] FIG. 24A diagrammatically illustrates an exemplary catheter comprising a handle and an elongated shaft constructed in accordance with the principles of the present disclosure.

[0073] [Figure 24B]FIG. 24B diagrammatically illustrates another exemplary catheter including a handle and an elongated shaft constructed in accordance with the principles of the present disclosure.

[0074] [Figure 25A] FIG. 25A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0075] [Figure 25B] FIG. 25B illustrates the anchor of FIG. 25A in a deployed state.

[0076] [Figure 26A] FIG. 26A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0077] [Figure 26B] FIG. 26B illustrates the anchor of FIG. 26A in a deployed state.

[0078] [Figure 27A] FIG. 27A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0079] [Figure 27B] FIG. 27B illustrates the anchor of FIG. 27A in a deployed state.

[0080] [Figure 27C] FIG. 27C is a top view of an exemplary petal configuration for the anchor of FIG. 27A.

[0081] [Figure 27D] FIG. 27D is a side view of the petal configuration of FIG. 27C.

[0082] [Figure 28A] FIG. 28A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0083] [Figure 28B] FIG. 28B illustrates the anchor of FIG. 28A in a deployed state.

[0084] [Figure 28C] FIG. 28C illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0085] [Figure 28D] FIG. 28D illustrates the anchor of FIG. 28C in a deployed state.

[0086] [Figure 29A] FIG. 29A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0087] [Figure 29B] FIG. 29B illustrates the anchor of FIG. 29A in a deployed state.

[0088] [Figure 30A] FIG. 30A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0089] [Figure 30B] FIG. 30B illustrates the anchor of FIG. 30A in a deployed state.

[0090] [Figure 31A] FIG. 31A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0091] [Figure 31B] FIG. 31B illustrates the anchor of FIG. 31A in a deployed state.

[0092] [Figure 32A]FIG. 32A illustrates another exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0093] [Figure 32B] FIG. 32B illustrates the anchor of FIG. 32A in a deployed state.

[0094] [Figure 33A] FIG. 33A illustrates an exemplary anchor constructed in accordance with the principles of the present disclosure in a collapsed delivery state.

[0095] [Figure 33B] FIG. 33B illustrates the anchor of FIG. 33A in a deployed state.

[0096] [Figure 33C] 33C and 33D illustrate various views of an exemplary loop wire. [Figure 33D] 33C and 33D illustrate various views of an exemplary loop wire.

[0097] [Figure 34A] FIG. 34A illustrates an exemplary catheter within a vessel that is not properly anchored.

[0098] [Figure 34B] FIG. 34B illustrates an exemplary catheter in which the stiffness of the shaft proximate the distal portion can be virtually eliminated.

[0099] [Figure 35A] FIG. 35A illustrates an exemplary setback feature constructed in accordance with the principles of the present disclosure.

[0100] [Figure 35B] FIG. 35B illustrates another exemplary setback feature constructed in accordance with the principles of the present disclosure.

[0101] [Diagram 36]FIG. 36 is a schematic diagram of an exemplary ablation instrument in accordance with the principles of the present disclosure.

[0102] [Figure 37A] FIG. 37A illustrates an exemplary catheter including a sensor constructed in accordance with the principles of the present disclosure.

[0103] [Figure 37B] FIG. 37B is a graph depicting exemplary temperature measurements and pulse emissions during ablation.

[0104] [Figure 37C] FIG. 37C illustrates an exemplary catheter system including a second catheter equipped with a sensor, constructed in accordance with the principles of the present disclosure.

[0105] [Figure 37D] FIG. 37D illustrates a sensor coupled to the interior of an exemplary lens.

[0106] [Figure 37E] FIG. 37E illustrates multiple sensors located on an exemplary anchor in accordance with the principles of the present disclosure.

[0107] [Figure 38A] 38A-38B illustrate an exemplary method of inserting and navigating a catheter into a vessel in accordance with the principles of the present disclosure. [Figure 38B] 38A-38B illustrate an exemplary method of inserting and navigating a catheter into a vessel in accordance with the principles of the present disclosure.

[0108] [Figure 38C] 38C-38D illustrate an exemplary method of treating tissue surrounding the right pulmonary artery in accordance with the principles of the present disclosure. [Figure 38D] 38C-38D illustrate an exemplary method of treating tissue surrounding the right pulmonary artery in accordance with the principles of the present disclosure.

[0109] [Figure 38E] 38E-38F illustrate an exemplary method of treating tissue surrounding the left pulmonary artery in accordance with the principles of the present disclosure. [Figure 38F] 38E-38F illustrate an exemplary method of treating tissue surrounding the left pulmonary artery in accordance with the principles of the present disclosure.

[0110] [Figure 38G] 38G-38I illustrate an exemplary method of treating tissue surrounding the pulmonary trunk in accordance with the principles of the present disclosure. [Fig. 38H] 38G-38I illustrate an exemplary method of treating tissue surrounding the pulmonary trunk in accordance with the principles of the present disclosure. [Fig. 38I] 38G-38I illustrate an exemplary method of treating tissue surrounding the pulmonary trunk in accordance with the principles of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0111] Detailed Description The interplay of the vasoconstriction / vasodilator axis of the pulmonary circulation is one of the important determinants of pulmonary hypertension disease progression and severity. The sympathetic nervous system mediates pulmonary vasoconstriction. This can be specifically accomplished by the thoracic sympathetic chain and its branches. The sympathetic nervous system can be important in mediating the hypoxia-mediated vasoconstrictor response of the pulmonary arterial vasculature. Modulating or reducing sympathetic nervous system activity in the pulmonary vasculature is a unique approach for the treatment of pulmonary hypertension. Reducing, modulating, and / or eliminating sympathetic tone to the pulmonary arteries reduces sympathetically mediated vasoconstriction, thereby allowing increased pulmonary vascular diameter and pulmonary vascular opening. The net effect of reducing sympathetic tone is a reduction in pulmonary pressure and pulmonary hypertension, which is a possible goal of therapy.

[0112] Although the present detailed description will focus on treating sympathetic nerves, nerve fibers, and / or neurons in any given embodiment, the methods, devices, or systems described herein may also, or alternatively, treat parasympathetic nerves, nerve fibers, and / or neurons, and thus, descriptions herein of treating sympathetic tissue should not be construed as limiting.

[0113] Pulmonary Neurovascular Anatomy Sympathetic innervation of the lungs and heart originates from the thoracic and lumbar spine and eventually reaches the heart and lungs to innervate their vasculature. The sympathetic nervous system is part of the autonomic nervous system, comprising nerve fibers that branch off from the spinal cord in the thoracic and lumbar regions and supply the visceral organs and blood vessels via chains of sympathetic ganglia that extend on each side of the spinal column, communicating with the central nervous system via branches to corresponding spinal nerves. Sympathetic nerves, which originate primarily from the thoracic spine (e.g., levels T1-T10, with some potential contribution from the cervical vertebrae), innervate the heart and lungs after branching off from the thoracic sympathetic chain. The sympathetic nerves converge on the thoracic sympathetic chain and ganglia, which then give rise to postganglionic sympathetic nerves, which then innervate the heart and lungs. These nerves often converge on various nerve collection networks or plexuses, which are often areas of convergence of both sympathetic and parasympathetic nerve fibers. These plexuses then give rise to further nerve branches or continuations that then branch and ramify onto structures within the heart and lungs, or in association with, for example, the outer walls of the pulmonary arteries or arterioles. Some of the important plexuses and their anatomical relationships to the heart, lungs, and pulmonary vasculature are described herein.

[0114] The great sympathetic plexuses are collections of nerves and ganglia anchored in the thoracic, abdominal, and pelvic cavities, called the cardiac, celiac, and hypogastric plexuses. They contain not only sympathetic fibers derived from the ganglia, but also fibers from the spinal cord, conveyed via the white rami communicans. From the plexuses, branches are given to the thoracic, abdominal, and pelvic viscera.

[0115] The cardiac plexus is divided into a superficial portion, which is anchored at the base of the heart and lies within the concavity of the aortic arch, and a deep portion, which lies between the aortic arch and the trachea. The superficial and deep portions are closely connected.

[0116] The superficial part of the cardiac plexus lies immediately below the aortic arch, in front of the right pulmonary artery. It is formed by the superior cardiac branch of the left sympathetic nerve and the inferior superior cervical cardiac branch of the left vagus nerve. A small ganglion, the cardiac ganglion of Wrisberg, is occasionally found connected with these nerves at their junction. This ganglion, when present, is anchored immediately below the aortic arch, to the right of the ligamentum arteriosum. The superficial part of the cardiac plexus gives rise to branches into (a) the deep part of the plexus, (b) the anterior coronary plexus, and (c) the left anterior pulmonary plexus.

[0117] The deep part of the cardiac plexus is anchored in front of the bifurcation of the trachea, above the division of the pulmonary artery, and behind the aortic arch. It is formed by the cardiac nerves, which arise from the cervical ganglion of the sympathetic nerves, and the cardiac branches of the vagus and recurrent laryngeal nerves. The only cardiac nerves that do not enter into the formation of the deep part of the cardiac plexus are the superior cardiac nerve of the left sympathetic nerve and the lower part of the two superior cervical cardiac branches from the left vagus nerve, which pass into the superficial part of the plexus.

[0118] Branches from the right half of the deep part of the cardiac plexus, some in front and others behind it, pass into the right pulmonary artery and are more numerous than those behind; those in front of the pulmonary artery pass a few filaments into the anterior pulmonary plexus and then continue anteriorly to form part of the anterior coronary plexus, while those behind the pulmonary artery distribute a few filaments into the right atrium and then continue anteriorly to form part of the posterior coronary plexus.

[0119] The left half of the deep part of the plexus connects with the superficial part of the cardiac plexus, gives off filaments to the left atrium and anterior pulmonary plexus, and then continues to form the larger part of the posterior coronary plexus.

[0120] The posterior coronary plexus (posterior coronary plexus; left coronary plexus) is larger than the anterior coronary plexus and accompanies the left coronary artery. It is formed mainly by filaments extending from the left half of the deep part of the cardiac plexus and a few from the right half. The posterior coronary plexus gives branches to the left atrium and ventricle.

[0121] The anterior coronary plexus (anterior coronary plexus; right coronary plexus) is formed partly from the superficial and partly from the deep part of the cardiac plexus. It accompanies the right coronary artery. It gives branches to the right atrium and ventricle.

[0122] The pulmonary plexus is the site of convergence of autonomic fibers that supply the lungs. It continues superiorly to the cardiac plexus and posteriorly and superiorly to the esophageal plexus.

[0123] The pulmonary plexuses are anchored anteriorly and posteriorly to each lung root. They are in close proximity to the pulmonary arteries, and as they branch laterally, they ramify their nerve fibers in association with the outer walls of the diverging pulmonary arteries and arterioles.

[0124] Fibers from the cardiac plexus pass inferiorly, in front of the trachea and behind the aortic arch. The pulmonary plexus also receives autonomic fibers directly from other sources. It receives parasympathetic fibers directly from the right vagus nerve, which descends posteriorly and inferiorly over the trachea, where it divides and gives rise to the pulmonary and esophageal plexuses, which pass anterior to the lung root. It also receives parasympathetic fibers directly from the left vagus nerve, which descends anteriorly to the aortic arch and gives rise to the recurrent pharyngeal branch, whose fibers then diverge anteriorly to supply the left pulmonary plexus. The pulmonary plexus receives sympathetic fibers directly above the branches of the four thoracic ganglia, which pass anteriorly around the posterior thorax and merge on the lateral wall of the esophagus. The branches supply the pulmonary plexus with nerve fibers from the region dorsal to the carina of the trachea.

[0125] The recurrent cardiac nerve and occasionally the cranial vagal cardiac nerve can carry the main innervation of the pulmonary bifurcation and adjacent portions of the main pulmonary artery and its right and left branches. The recurrent cardiac nerve is a medium-sized nerve that arises from the right recurrent laryngeal nerve as it loops around the right subclavian artery. The recurrent cardiac nerve usually receives variable-sized contributions from the vagus nerve, the parasympathetic trunk, and another from the stellate ganglion. The nerve passes dorsally to the anterior vena cava and laterally to the brachiocephalic artery and aortic arch up to the pulmonary bifurcation where it divides into anterior and posterolateral branches. The anterior lateral branches tend to be smaller. The branches then tend to spread over the anterior and posterior aspects of the main pulmonary artery and communicate with the nerve plexus around the right and left pulmonary arteries and the pretracheal plexus. Some fibers continue to the heart and coronary nerve plexus. During its course, it communicates freely with the cranial vagal cardiac nerve.

[0126] The right vagus cardiac nerve arises from the right vagus trunk caudal to the origin of the right recurrent laryngeal nerve. They are divided into two groups, the cranial and caudal vagus cardiac nerves. They vary in size, number, and course. With the inclusion of some of its smaller divisions, the right vagus cardiac nerve supplies branches or tributaries to the right pulmonary plexus, a plexus formed by the anterior and posterolateral branches of the right recurrent cardiac nerve at the pulmonary bifurcation, and the ventral branch of the vagus nerve anterior to the pulmonary root, and then terminates at the atrial wall. Small branches or tributaries, variable in size and location and sometimes absent, supply the pretracheal plexus and plexuses around the right and left pulmonary arteries by the right stellate cardiac nerve, the ventral medial cervical cardiac nerve, the left recurrent laryngeal nerve, and the ventral branch of the left vagus trunk. Other branches or tributaries are also supplied by a diffuse plexus of fibers, forming the ventral lateral cardiac nerve and the left stellate cardiac nerve.

[0127] One of these nerves that is of interest is the recurrent cardiac nerve, particularly the right recurrent cardiac nerve, since it may contain, among other things, preganglionic, afferent, and sympathetic postganglionic fibers. The recurrent cardiac nerve is a branch of the right recurrent laryngeal nerve, a nerve of the visceral arch. It is therefore of great interest that the main innervation to the pulmonary carina sensory area, which is part of the visceral arch, is derived from the recurrent laryngeal nerve, a nerve of the visceral arch. Since the most cranial part of the pulmonary artery is formed from the posterior and right lateral part of the cardiac bulb, this vessel is mainly supplied by the right splanchnic nerve.

[0128] More specifically, the pulmonary artery bifurcation and adjacent parts of the right and left pulmonary arteries receive a very rich innervation. On the right side, the most constitutive nerve trunk to the bifurcation is the right recurrent cardiac nerve. Fibers arise from the vagus nerve or recurrent laryngeal nerve as it loops around the subclavian artery immediately caudal to its origin from the brachiocephalic trunk. The nerve proceeds medially and caudally, passing dorsal to the superior vena cava and lateral to the origin of the brachiocephalic trunk. The fibers branch at the bifurcation by dividing into anterior-lateral and posterolateral branches, which communicate with fibers from the pulmonary plexus. During its course, it usually communicates with one or more right vagus cardiac nerves of very small size, which branch off from the stellate ganglion or subclavian ganglion. These latter branches are thought to contribute to the efferent component. Minor variations in the mode of origin from the recurrent laryngeal nerve (RLN) have been noted. In some cases, the nerve may arise from the loops of the RLN as a separate nerve trunk, joined by cardiac sympathetic branches from the adjacent stellate ganglion. The recurrent cardiac nerve may also arise, rarely, from the angle of origin of the RLN. In some cases, the main part of the nerve may arise from the vagus nerve and as the vagus cardiac nerve, which receives small filaments from the RLN.

[0129] Contributions to the innervation of the pulmonary artery from the left side are similar to those of the right side, but also, in some cases, always receive a small direct contribution from the vagus nerve in the form of the ventral medial cervical cardiac nerve. This nerve arises from the vagus nerve by a variable number of roots, usually two, and proceeds caudally, passing over the aortic arch, branching into the ligamentum arteriosum, the pulmonary bifurcation, and the left pulmonary artery. The superior cranial vagus root usually receives a direct branch from the left stellate ganglion. The bifurcation and the left pulmonary artery receive small non-permanent branches from the RLN as they pass under the aortic arch. In some cases, a descending branch arises from the ascending portion of the RLN and terminates around the bifurcation.

[0130] The pulmonary musculature receives primarily right-sided innervation from adrenergic sympathetic fibers that cause vasoconstriction, but little or no motor innervation from the parasympathetic or vagus nerves. The fibers synapse primarily in the stellate ganglion, but also in the upper thoracic and sympathetic ganglia. Large concentrations of nerve endings are found at the bifurcation of the pulmonary artery and in the adjacent pulmonary artery and parts of its right and left main branches.

[0131] Beyond the main pulmonary arteries, i.e., the right and left main pulmonary arteries, the innervation of the further branches of the lung follows the arterial anatomy, and the nerves that run along the arteries typically follow a periadventitial location or run along the adventitia. Extensive innervation exists within the pulmonary arteries further distal to the pulmonary arterioles, which are on the order of 30 microns in diameter or smaller. This innervation includes both parasympathetic and sympathetic innervation, and the lung is considered to have a rich sympathetic innervation.

[0132] Thoracic sympathectomy is a surgical procedure that currently exists and is utilized in the treatment of a different disease process, namely hyperhidrosis syndrome (excessive sweating). Extensive research on this surgical procedure has shown it to be safe and effective. Physiological studies of patients undergoing thoracic sympathectomy have shown mild changes in pulmonary function and mild increases in airway resistance, a slight decrease in heart rate, however, preserved left ventricular function and ejection fraction, and also preserved exercise tolerance. Data from T2-T3 video-assisted thoracoscopic sympathectomy patients indicate that sympathectomy results in the disconnection of ipsilateral hypoxia-mediated vasoconstrictor pathways to the pulmonary vasculature by demonstrating a drop in arterial oxygen saturation during contralateral selective pulmonary ventilation, both prior to and following sympathectomy. This implies ipsilateral pulmonary vascular enlargement and a reduction in pulmonary pressure. Thoracic sympathectomy has been used to treat hyperhidrosis, but prior to the provisional patent application from which this application claims priority, it has not been described to treat pulmonary hypertension. More generally, decreasing the activity of one or more sympathetic nerves or neurons to reduce pulmonary vascular resistance and / or ameliorate pulmonary hypertension has not previously been described.

[0133] Treatment Devices 1A and 1B, an exemplary catheter system for reducing neural activity of nerves surrounding a patient's blood vessel, e.g., a pulmonary artery, is provided. For example, neural activity may be reduced by inactivating the nerve. The catheter system 100 may include a proximal region 102, a distal region 104, and an elongated shaft 101 extending between the proximal region 102 and the distal region 104. The catheter system 100 may further include an anchor 200 and a transducer 114 disposed in the distal region 104, and a handle 300 disposed in the proximal region 102. The handle 300 may be operably coupled to the anchor 200 and the transducer 114, for example, through the elongated shaft 101, such that the handle 300 may be actuated by a user by actuating the anchor 200 and the transducer 114. For example, the handle 300 may be used to guide the distal region 104 to a target location within a blood vessel and then actuated to deploy the anchor 200 within the blood vessel, thereby causing the transducer 114 to be centered within the blood vessel. The handle 300 may further be actuated to cause the transducer 114 to emit energy into the blood vessel, reducing neural activity in nerves surrounding the blood vessel. The handle 300 may also be used to reposition the distal region 104 to another portion of the blood vessel, e.g., from the right pulmonary artery to the left pulmonary artery and / or main pulmonary artery, such that neural activity in nerves surrounding other portions of the blood vessel may also be reduced via the transducer 114. Upon completion of the ablation therapy, the catheter system 100 may be removed from the patient.

[0134] 1B, the elongated shaft 101 is described. As shown in FIG. 1B, the elongated shaft 101 may include multiple catheters, such as an inner catheter 110, a transducer shaft 112, an outer catheter 116, a sheath 118, and a separation sleeve 120. For example, the inner catheter 110 may be the innermost catheter of the elongated shaft 101 and may have a proximal region operably coupled to the handle 300 and a distal region having an atraumatic tip 111. The inner catheter 110 may have a lumen extending therethrough, including through the tip 111, such that the lumen is sized and shaped to receive a guidewire therethrough. For example, the guidewire lumen may be 0.050 inches to 0.080 inches along the length of the inner catheter 110, and may guide a guidewire that is, for example, 0.035 inches or smaller. Thus, the proximal end of the guidewire may be fed through the lumen of the tip 111 such that the catheter system 100 is advanced over the guidewire to position the distal region 102 at a target location within a blood vessel, as described in more detail below. The inner catheter 110 may be actuable via the handle 300 to translate the inner catheter 110 relative to the handle 300.

[0135] The catheter system 100 may include a transducer assembly, which includes a transducer shaft 112 having a proximal region operably coupled to the handle 300, and a transducer 114 disposed at a distal region of the transducer shaft 112. The transducer shaft 112 may have a cylindrical shape and a lumen extending therethrough such that the lumen is sized and shaped to slidably receive the inner catheter 110 therein. Thus, the inner catheter 110 may move relative to the transducer shaft 112. The transducer 114 may be configured to effect neuromodulation, for example, via ablation, denervation, which may or may not be reversible, stimulation, etc. For example, the transducer 114 may convert electrical input into an acoustic beam that will be absorbed by the target tissue and induce heating of the nerve surrounding / innervating the blood vessel, thereby reducing neural activity of the nerve. For example, the transducer 114 may be an arcuate ultrasound transducer having a piezoelectric element for emitting ultrasound energy, e.g., focused or unfocused ultrasound. Alternatively, the transducers described herein may be configured to emit radio frequency (RF) energy, microwave energy, cryoenergy, thermal energy, electrical energy, infrared energy, laser energy, phototherapy, plasma energy, ionization energy, mechanical energy, chemical energy, combinations thereof, and the like.

[0136] The outer catheter 116 may have a proximal region operably coupled to the handle 300 and a lumen extending therethrough such that the lumen is sized and shaped to receive the transducer shaft 112 therein. A distal region of the outer catheter 116 may be coupled to the transducer 114 and the transducer shaft 112. For example, the distal region of the outer catheter 116 may be sealed with the distal region of the transducer shaft 112 to create a fluidically sealed cavity therebetween. Additionally, at least one cable may be disposed within the fluidically sealed cavity and electrically coupled to the transducer 114 to provide electrical energy to the transducer 114. The outer catheter 116 may be operable via the handle 300 to translate the outer catheter 116 relative to the handle 300. Thus, the outer catheter 116 may move relative to the inner catheter 110.

[0137] 1B, the proximal end of the anchor 200 may be coupled to the outer catheter 116 and the distal end of the anchor 200 may be coupled to the inner catheter 110. Thus, relative movement between the inner catheter 110 and the outer catheter 116, e.g., via a push-pull mechanism, may transition the anchor 200 between a collapsed delivery state and an expanded deployed state. For example, moving the inner catheter 110 distally relative to the outer catheter 116 may collapse the anchor 200 toward the longitudinal axis of the elongate shaft 101, and moving the inner catheter 110 proximally relative to the outer catheter 116 may expand the anchor outwardly from the longitudinal axis of the elongate shaft 101. In the expanded deployed state, the anchor 200 may contact the inner wall of the blood vessel and center the transducer 114 within the vessel. Thus, in the expanded, deployed state, the anchor 200 can have a radial force that exceeds the stiffness force of the inner catheter 110, the transducer shaft 112, the outer catheter 116, and the distal region 118b of the sheath 118. The anchor 200 may be configured to preserve blood flow through the vessel in the expanded, deployed state.

[0138] The sheath 118 may have a proximal region 118a operably coupled to the handle 300, a distal region 118b, and a lumen extending therethrough such that the lumen is sized and shaped to slidably receive the outer catheter 116 and the anchor 200 in its collapsed delivery state. The proximal region 118a may have a longer and thinner profile than the distal region 118b to reduce the force of the elongated shaft 101 against the patient's anatomy. Reducing this force reduces the amount of force required to center the transducer 114 by the anchor 200. However, this reduction in force in the proximal region 118a must be balanced against the stiffness of the distal region 118b of the sheath 118 required to cover the anchor 200. For example, the distal region 118b should be stiff enough to slide over the anchor 200 without compressing or buckling. This feature may be addressed not only through proper material selection, proper braiding (wire profile and PPI), but also through pre-conditioning of the sheath 118 prior to its integration into the catheter system 100.

[0139] The distal region 118b of the sheath 118 may have sufficient stiffness to facilitate transition of the anchor 200 from an expanded deployed state to a collapsed delivery state in response to movement of the distal region 118b distal to the anchor 200 without buckling the distal region 118b. Thus, the distal region 118b may have a stiffness that exceeds the stiffness of the proximal region 118a of the sheath 118. For example, as shown in FIG. 1B, the distal region 118b may have an outer diameter that is larger than the outer diameter of the proximal region 118a, e.g., the distal region 118b may have a cross-sectional area that is larger than the cross-sectional area of ​​the proximal region 118a. Thus, the proximal region 118a may be more flexible to facilitate navigation of the catheter system 100 through the patient's vasculature. Additionally, the sheath 118 may be moved distally relative to the inner catheter 110 such that the anchor 200, in its collapsed delivery state, is disposed within the lumen of the sheath 118, e.g., within the distal region 118b, and the distal end of the distal region 118b engages the proximal end of the tip 111, thereby forming a seal, such that the catheter system 100 is in the delivery configuration. Thus, the distal region 118b may have an outer diameter that is substantially equal to the outer diameter of the proximal end of the tip 111, in the delivery configuration, providing a smooth and / or continuous outer surface.

[0140] The separator sleeve 120 may be fixedly coupled to the handle 300 and may have a lumen extending therethrough such that the lumen is sized and shaped to slidably receive at least the proximal region 118a of the sheath 118 therein. Thus, the sheath 118 may move relative to the separator sleeve 120, for example, when the sheath 118 is actuated via the handle 300. The separator sleeve 120 may extend along at least a portion of the proximal region of the elongate shaft 101. Preferably, the separator sleeve 120 does not extend along the entire length of the elongate shaft 101 to provide a smaller footprint and greater flexibility for the catheter system 100.

[0141] The separation sleeve 120 may be configured to allow the handle 300 to be fixed relative to the patient. For example, the catheter system 100 may further include an introducer, which may be inserted into and fixed relative to the patient at an entry site. The introducer may have a lumen extending therethrough, such that, for example, in a delivery configuration, the lumen is sized and shaped to slidably receive the elongate shaft 101 therethrough. For example, the tip 111 may be advanced over a guidewire and through the lumen of the introducer such that the elongate shaft 101 is delivered through the introducer and through the patient's vasculature. During uninsertion and reinsertion of the anchor 200 and transducer 114 via proximal and distal translational movement of the sheath 118 relative to the anchor 200 and transducer 114, it may be desirable to fix the position of the handle 300 relative to the patient so that inadvertent movement of the transducer 114 and / or anchor 200 may be avoided as the sheath 118 is moved relative to the handle 300. Thus, the separation sleeve 120 may be fixedly coupled to the introducer, which is fixedly coupled to the patient. For example, the transducer may have a valve disposed within the lumen of the introducer such that when the separation sleeve 120 is disposed within the lumen of the introducer, the valve is actuated relative to the separation sleeve 120 in response to actuation thereof. By fixing the position of the separation sleeve 120, which is fixedly coupled to the handle 300, relative to the introducer, which is fixedly coupled to the patient, the handle 300, and therefore the transducer 114 and / or anchor 200, will also be fixed relative to the patient and therefore the blood vessel such that the sheath 118 may be moved proximally and distally relative to the transducer 114 and / or anchor 200 while the transducer 114 and / or anchor 200 remain unmoved relative to the blood vessel.

[0142] The elongated shaft 101 may include additional lumens. For example, an optional lumen may be used to track the catheter system 100 over a guidewire. In addition, an optional lumen may provide a passage for a conductor wire, e.g., cable 600, between the transducer 114 and a signal generating system. In addition, an optional lumen may provide a passage for a conductor wire between a sensor and a receiving station. Furthermore, an optional lumen may be provided to deliver a coolant to the transducer 114 during ultrasonic vibration / ablation. For example, cold saline may be delivered through the lumen, e.g., via a pressure bag or a dedicated infusion pump, through an outlet located near the transducer to cool the transducer and the surrounding blood that is heated by the Joule effect of the transducer.

[0143] 2A-2C, the distal region 104 of the catheter system 100 will be described. The distal region 104 is sized and shaped to be placed in a blood vessel, for example, the right, left, and / or main pulmonary artery. As shown in FIGS. 2A and 2B, the proximal end 202 of the anchor 200 may be coupled to the outer catheter 116 at an axial location proximal to the transducer 114, and the distal end 204 of the anchor 200 may be coupled to the inner catheter 110 at an axial location distal to the transducer 114, such that the transducer 114 is placed within the anchor 200. The anchor 200 may be formed from a shape memory material, for example, Nitinol, Chrome Cobalt, MP35N, 35NPT, Elgiloy, and the like. 2A and 2B, the anchor 200 may be formed from multiple struts extending from a proximal end 202 to a distal end 204 of the anchor 200. The multiple struts may be cut (e.g., laser cut) from a hypotube or sheet. For example, the multiple struts may include multiple connections forming diamond-shaped struts, which in the expanded deployed state form a cage and prevent bunching of the struts while being pressed against the vessel wall. Thus, in the expanded deployed state, the anchor 200 may allow the transducer 114 to be centered within the vessel while not occluding the vessel, thereby preserving blood flow through the vessel.

[0144] The anchor 200 is configured to center the transducer 114 in both straight or curved vessels, which can help ensure that tissue all around the vessel is treated. In a curved vessel, the radial force exerted by the anchor 200 on the inner wall of the vessel must overcome the inherent force from the stiffness of the elongated shaft 101 to center the transducer 114 in the curved vessel. The radial force of the anchor 200 is derived from the material composition of the anchor 200, e.g., Nitinol, and the longitudinal compression of the anchor 200. The anchor 200 may have a rectangular profile to avoid multiple struts sliding across the inner wall of the vessel.

[0145] As described above, relative movement between the inner catheter 110 and the outer catheter 116 may transition the anchor 200 between a collapsed delivery state and an expanded deployed state. Preferably, the outer catheter 116 is fixed relative to the handle 300, and the inner catheter 110 may be actuated via the handle 300 to move proximally and distally relative to the outer catheter 116 to expand and collapse the anchor 200, as described in more detail below with respect to Figures 4B and 4C. Alternatively, the inner catheter 110 may be fixed relative to the handle 300, and the outer catheter 116 may be actuated via the handle 300 to move proximally and distally relative to the outer catheter 116 to expand and collapse the anchor 200. In this configuration, the outer catheter 116 may be retracted proximally relative to the sheath 118 and the inner catheter 110, for example, by retracting the proximal end of the anchor 200 into the sheath 118, thereby retracting and collapsing the anchor 200 into the sheath 118. In another alternative embodiment, the inner catheter 110 and the outer catheter 116 may both be actuated via the handle 300, for example, via a single actuator operably coupled to both the inner catheter 110 and the outer catheter 116 such that actuation of the single actuator moves the inner catheter 110 and the outer catheter 116 toward and away from one another in equal and opposite directions.

[0146] In yet another alternative embodiment, the anchor 200 may be formed from a self-expanding material such that the anchor 200 is biased toward the expanded, deployed state. Additionally, the distal end of the anchor 200 may be coupled to the inner catheter 110 via a ring that is slidably disposed on the inner catheter 110 such that the distal end of the anchor 200 is slidably coupled to the inner catheter 110. Thus, upon retraction of the sheath 118 to expose the anchor 200 within the vessel, the anchor 200 may self-expand as the ring slides across the inner catheter 110, allowing the distal end of the anchor 200 to move proximally toward the proximal end of the anchor 200. In this configuration, reinsertion of the anchor 200 through the sheath 118 requires little force since the distal end of the anchor 200 is not secured to the inner catheter 110 and the sheath 118 retracts the tip / inner material and does not need to reinsert the anchor 200. Additionally, it may allow for the use of more flexible materials, reducing forces on the patient anatomy and making the catheter system 100 easier to navigate within small anatomy.

[0147] Alternatively, the anchor 200 may be formed from a self-expanding material such that the anchor 200 is biased toward the collapsed delivery state. In this configuration, more longitudinal force would be required to move the inner catheter 110 and the outer catheter 116 toward each other and expand the anchor 200. However, the distal region 118b requires less stiffness and may therefore be more flexible since the distal region 118b would not require as much stiffness to collapse and cover the anchor 200. Additionally, the anchor 200 would have to compete less against the stiffness of the elongated shaft 101 to induce centering of the transducer 114. Additionally, reducing the profile of the catheter assembly in the section proximal to the transducer 114 may prevent or otherwise limit cardiac compression and may also limit valvular regurgitation while the transducer 114 is located within the pulmonary artery, which may be beneficial for pulmonary hypertension patients as they may only accommodate a limited period of cardiac compression during catheter delivery.

[0148] In the expanded, deployed state, the anchor 200 can have a cross-sectional area that corresponds to a cross-sectional area of ​​a blood vessel such that the anchor 200 applies sufficient force to the inner wall of the blood vessel to anchor and center the transducer 114 within the blood vessel. Preferably, the anchor 200 does not dilate the blood vessel in the expanded, deployed state. Thus, relative movement between the inner catheter 110 and the outer catheter 116 can be selectively actuated via the handle 300 to expand the anchor 200 to a predetermined size corresponding to the target vessel.

[0149] As further shown in FIGS. 2A and 2B, the atraumatic tip 111 may have a tapered profile. For example, the cross-sectional area of ​​the tip 111 may decrease from the proximal end of the tip 111 toward the distal end of the tip 111. The tapered profile is gradual to guide the distal region 118b of the sheath 118 during reinsertion of the anchor 200 in both straight and curved configurations, e.g., in the curved portion of the pulmonary artery. Additionally, the taper ensures that no gap exists between the tip 111 and the distal region 118b in the reinserted delivery configuration, preventing tissue pinching during reinsertion and navigation through the patient's vasculature. The tip 111 may be made of a soft material with a thickness selected to prevent from damaging the IVC or SVC, right atrium, right ventricle, valves, and pulmonary artery during catheter navigation.

[0150] As shown in FIG. 2C, the sheath 118 may be a flexible coil, e.g., laser cut stainless steel, to provide sufficient flexibility to prevent buckling of the distal region 118b and facilitate collapse of the anchor 200 into the lumen of the sheath 118 as the sheath 118 is advanced distally relative to the anchor 200, while limiting the compressibility of the sheath 118. This is beneficial because femoral access in humans constrains the catheter into an "S" shape, and the smaller the anatomy, the smaller the bending radius of the two inclinations of the "S", leading to maximization of forces between the catheter and the RA (right atrium) or RV (right ventricle). These forces may lead to cardiac compression, which is unfavorable for the treatment of pulmonary hypertension patients. To limit these forces, the stiffness of the catheter may be reduced, which is determined by the stiffness of its stack of shafts. The stiffness of the shaft depends on several properties, such as the material of the material or the wall thickness. Additionally, the elongated shaft 101 must also support the force of the anchor 200 and either collapse or compress the anchor 200. Thus, the elongated shaft 101 must have a limited compressibility, for example, limited to 2 mm over a maximum 2 meter tubing run. Thus, forming the sheath 118, inner catheter 110, and / or outer catheter 116 from a flexible coil, for example, laser cut stainless steel, may provide sufficient flexibility while limiting the compressibility. Alternatively, the elongated shaft 101 may be preconditioned in a fixture in a heated environment, which forces the elongated shaft 101 to compress before integration into the catheter system 100. Thus, the elongated shaft 101 may also be preconditioned for its elongation.

[0151] 3, a handle 300 is described. The handle 300 may include a frame 302 and one or more actuators, such as knobs 304 and 306, and / or thumb wheels or sliders. The knob 304 may be operatively coupled to at least one of the inner catheter 110 or the outer catheter 116 and may be configured to be rotated to cause relative movement between the inner catheter 110 and the outer catheter 116, thereby transitioning the anchor 200 between a collapsed delivery state and an expanded deployed state. For example, rotating the knob 304 in a first direction may move the inner catheter 110 and the outer catheter 116 toward one another, thereby deploying the anchor 200 to the expanded deployed state, and rotating the knob 304 in a second direction opposite the first direction may move the inner catheter 110 and the outer catheter 116 away from one another, thereby collapsing the anchor 200 to the collapsed delivery state. As the user actuates knob 304, the user may be able to feel when the struts of anchor 200 contact the vessel wall and may stop the expansion of anchor 200 at the appropriate deployment state.

[0152] The knob 304 may be operably coupled only to the inner catheter 110 such that rotation of the knob 304 moves the inner catheter 110 relative to the outer catheter 116. Alternatively, the handle 300 may include separate actuators operably coupled to each of the inner catheter 110 and the outer catheter 116 such that the inner catheter 110 and the outer catheter 116 may be independently actuable.

[0153] The knob 306 may be operatively coupled to the sheath 118 and may be configured to be rotated to cause movement of the sheath 118 relative to the handle 300 and other components of the catheter system 100, such as the anchor 200 and the transducer 114, thereby uninserting or reinserting the anchor 200 and the transducer 114. For example, rotating the knob 306 in a first direction may retract the sheath proximally relative to the anchor 200 and the transducer 114, thereby exposing the anchor 200 and the transducer 114, and rotating the knob 306 in a second direction opposite the first direction may move the sheath 118 distally relative to the anchor 200 and the transducer 114, thereby covering the anchor 200 and the transducer 114. Knobs 304 and 306 may be selectively actuated together to facilitate collapsing of anchor 200 into the lumen of sheath 118. For example, knob 304 may be rotated to move inner catheter 110 and outer catheter 116 away from one another, thereby collapsing anchor 200 to a collapsed delivery state, while knob 306 may be simultaneously rotated to move the sheath distally relative to anchor 200, thereby pushing against anchor 200 and facilitating collapse of anchor 200 into the lumen of sheath 118.

[0154] 4A-4E, the internal components of the handle 300 are provided. FIG. 4A is a cross-sectional view of the catheter system 100, and in particular the handle 300. FIG. 4B is an enlarged view of the circle 4B of FIG. 4A, FIG. 4C is an enlarged view of the circle 4C of FIG. 4A, FIG. 4D is an enlarged view of the circle 4D of FIG. 4A, and FIG. 4E is an enlarged view of the circle 4E of FIG. 4A. As shown in FIG. 4B, the handle 300 may include an inner catheter hub 308 that is operably coupled to a proximal region of the inner catheter 308. The inner catheter hub 308 may be operably coupled to the knob 304, for example, via the protrusions 309 of the hub 308 and the grooves 305 of the knob 304, such that as the knob 304 is rotated, the rotation of the grooves 305 causes the protrusions 309 to move along the grooves 305, which causes a translational movement of the hub 318 and thus the inner catheter 110.

[0155] 4C, the handle 300 may include an outer catheter hub 310 that is operably coupled to a proximal region of the outer catheter 116. The hub 310 may be configured to fixedly couple the outer catheter 116 to the handle 300 and may include a hub cap 314 and a sealing ring 316, e.g., an O-ring, to seal the lumen of the outer catheter 116 while allowing the inner catheter 110 to pass therethrough.

[0156] 4D , the handle 300 may include a sheath hub 318 operably coupled to a proximal region of the sheath 118. The sheath hub 318 may be operably coupled to the knob 306, for example, via protrusions 319 of the hub 318 and grooves 307 of the knob 306, such that as the knob 306 is rotated, rotation of the grooves 307 causes the protrusions 319 to move along the grooves 307, which causes translational movement of the hub 318 and thus the sheath 118.

[0157] 4E, the handle 300 may include a separation sleeve hub 324 operably coupled to a proximal region of the separation sleeve 120. The hub 324 may be configured to fixedly couple the separation sleeve 120 to the handle 300 and may include a hub cap 326 and a sealing ring 328, e.g., an O-ring, to seal the lumen of the separation sleeve 120 while allowing the sheath 128 to pass therethrough.

[0158] 5A and 5B, a deployment and delivery configuration of the catheter system 100 is provided. FIG. 5A illustrates the catheter system 100 in the delivery configuration. As shown in FIG. 5A, in the delivery configuration, the sheath 118 is advanced distally such that a distal end of the distal region 118b of the sheath 118 engages with a proximal end of the tip 111 and the anchor 200 is disposed within the lumen of the distal region 118b in its collapsed delivery state. The distal region 104 of the catheter system 100, in the delivery configuration, may be advanced, for example, through an introducer, over a guidewire, to a target location within a blood vessel.

[0159] Once the distal region 104 is at the target location within the vessel, the anchor 200 may be deployed and ready to center the transducer 114 within the vessel so that the transducer 114 may emit energy and provide ablation therapy. As explained above, the introducer may be actuated to fix the position of the handle 300 relative to the patient via the separation sleeve 120 once the transducer 114 is within the target location within the vessel. As shown in FIG. 5B, the sheath 118 may be retracted proximally relative to the anchor 200 and transducer 114, for example, by rotating the knob 306, while the anchor 200 and transducer 114 remain stationary relative to the target location within the vessel, thereby exposing the anchor 200 within the vessel. Depending on the exposure from the sheath 118, the anchor 200 may remain in the partially or completely collapsed delivery state. For example, the anchor 200 may be biased toward the expanded, deployed state, and relative movement of the inner catheter 110 and the outer catheter 116 may facilitate deployment of the anchor 200. Thus, when the anchor 200 is exposed from the sheath 118, at least a portion of the anchor 200 may begin to self-expand toward the expanded, deployed state. The knob 304 may then be rotated, as shown in FIG. 5B, to translate the inner catheter 110 proximally relative to the outer catheter 116, thereby deploying the anchor 200, which is coupled to both the inner catheter 110 and the outer catheter 116, to the expanded, deployed state.

[0160] With the anchor 200 properly deployed within the blood vessel, the transducer 114 may be centered within the blood vessel and activated to emit energy into the blood vessel to reduce neural activity in nerves surrounding the blood vessel. Once ablation therapy is completed at a target location within the blood vessel, the knob 304 may be rotated in the opposite direction to translate the inner catheter 110 distally relative to the outer catheter 116 in order to reposition the transducer 114 to a target location within another blood vessel, e.g., from the left pulmonary artery to the right pulmonary artery and / or main pulmonary artery, thereby transitioning the anchor 200 to a collapsed delivery state. In addition, knob 306 may also be simultaneously rotated in the opposite direction to transition sheath 118 distally relative to anchor 200, to promote collapse of anchor 200 to its collapsed delivery state, pushing against anchor 200 until the distal end of distal region 118b of sheath 118 engages anchor 200 and anchor 200 is disposed within the lumen of distal region 118b in the collapsed delivery state.

[0161] Alternatively, the knob 306 may be rotated to transition the sheath 118 distally relative to the anchor 200 after the inner catheter 110 has been moved distally relative to the outer catheter 116 such that the anchor 200 is at least partially in its collapsed delivery state. Thus, as the distal region 118b of the sheath 118 moves over the anchor 200, the anchor 200 will be received within the lumen of the distal region 118b in the collapsed delivery state. The sheath 118 may be moved until the distal end of the distal region 118b engages the tip 111 in the delivery configuration. The distal region 104 of the catheter system 100 may then be repositioned to position the transducer 114 at a target location within another blood vessel such that the anchor 200 may be redeployed and the transducer 114 may provide additional ablation therapy. Once all of the ablation therapy has been completed, the catheter system 100 may be returned to the delivery configuration and removed from the patient.

[0162] 6A-6D, a connection mechanism for an outer catheter 116 and a transducer assembly is provided. As shown in FIGS. 6A-6C, the transducer shaft 112 may be coupled to the transducer 114. A distal region of the transducer shaft 112 proximal to the transducer 114 may include one or more barb portions, such as barb portion 115. The barb portion 115 may be spaced a predefined distance from the proximal end of the transducer 114, thereby defining a gap 113. As shown in FIG. 6B, the gap 113 and the barb portions may extend circumferentially around the distal region of the catheter shaft 112. During assembly, the outer catheter 116 (not shown) may then be fed over the proximal end of the transducer shaft 112 until the distal end of the outer catheter 116 passes over the barb portion 115 and the gap 113 and engages the proximal end of the transducer 114. A material, for example, epoxy, may be added to fill the cavity formed between the gap 113 and the inner surface of the outer catheter 116 such that the outer catheter 116 and the transducer shaft 112 are sealed, creating a fluidically sealed cavity therebetween.

[0163] The outer diameter of the outer catheter 116 may be substantially equal to the outer diameter of the transducer 114, and the inner diameter of the lumen of the outer catheter 116 may be greater than the outer diameter of the transducer shaft 112, thereby providing a cavity between the inner surface of the outer catheter 116 and the outer surface of the transducer shaft 112. As described above, this cavity may be fluidly sealed. As shown in FIG. 6C, one or more cables, for example, cable 600, may be positioned within the fluidly sealed cavity to provide power to the transducer 114. For example, as shown in FIG. 6C, cable 600, which may be electrically insulated along substantially its entire length, may include a conductive portion 602 to electrically couple with the transducer 114.

[0164] A larger conductor diameter of cable 600 may be selected to limit heating of the coaxial cable during pulsing. However, having a cable with a larger diameter would require a larger diameter / thicker catheter. Therefore, instead of a single cable, multiple smaller coaxial cables may be placed along the length of elongated shaft 101, for example in a fluidically sealed cavity, doubling the conductor cross-sectional area without adding significant thickness to elongated shaft 101.

[0165] In addition, a pair of thermocouples, for example thermocouple 604, may also be positioned within the fluidically sealed cavity. FIG. 6D is a cross-sectional view of the transducer assembly where cable 600 and thermocouple 604 enter the proximal end of the barb portion 115 of the transducer shaft 112. For example, thermocouple 604 may be a type T thermocouple to monitor the transducer temperature at the interface with the blood flow. Thermocouple 604 may be located on the inner surface of the copper tape. Because copper and silver electrodes are very good thermal conductors, the temperature measured at this location represents the temperature of the outer surface of the transducer without interfering with the acoustic beam or adding additional thickness to the transducer assembly structure.

[0166] Additionally, one or more radiopaque markers may be located on the transducer assembly to allow a user to determine the positioning and / or orientation of the transducer 114 within the patient. For example, one or more radiopaque markers may be located in two perpendicular planes, respectively, relative to the positioning. Thus, when the transducer is configured such that at least a portion of the transducer emits little or no energy, e.g., forming a dead zone, as described in further detail below, the radiopaque markers may assist the user in determining the direction in which the dead zone is oriented to avoid creating lesions on sensitive anatomical structures, e.g., the phrenic nerve, recurrent laryngeal nerve, or other areas around the airway, e.g., the pulmonary artery, during the ablation procedure.

[0167] Referring now to FIG. 7, a method 700 for treating tissue using the catheter system described herein is provided. In step 702, an introducer may be set up. For example, the introducer may be inserted through an entry site within the patient, e.g., a venous access point, and secured relative to the patient. In step 704, a distal end of a guidewire may be inserted through the introducer and advanced into a target vessel, e.g., the pulmonary artery. For example, a Swan-Ganz catheter may first be inserted into the access point and floated to a target location within the target vessel. A guidewire may then be advanced through the Swan-Ganz catheter, which may be removed, leaving the guidewire in place from the access point to the target location. The guidewire may be steered, for example, under fluoroscopy, from the access point to the target location.

[0168] In step 706, the proximal end of the guidewire, external to the patient, may be inserted into the catheter system, e.g., through the lumen of the inner catheter 110, via the tip 111. In step 708, the handle 300 may be actuated to collapse the anchor 200, e.g., the expandable frame, and reinsert the anchor 200 into the sheath 118. For example, as described above, the knob 304 may be actuated to move the inner catheter 110 distally relative to the outer catheter 116 and transition the anchor 200 to the collapsed delivery state, and then the knob 306 may be actuated to move the sheath 118 distally relative to the anchor 200 until the anchor 200 is disposed within the distal region 118b of the sheath 118 and a distal end of the distal region 118b engages the tip 111. At step 710, the distal region 104 of the catheter system 100 may be advanced over the guidewire and through the introducer until the transducer 111 is positioned within the target location in the target vessel. In some embodiments, the catheter system 100 may include features of a Swan-Ganz catheter, such as a floatable balloon, so that the distal region 104 of the catheter system 100 may be inserted into an access point and floated to the target location.

[0169] At step 712, the handle 300 may be actuated to un-insert the anchor 200 and deploy the anchor 200 within the target vessel. For example, as described above, the knob 306 may be actuated to move the sheath 118 proximally relative to the anchor 200 until the anchor 200 is exposed from the sheath 118, and then the knob 304 may be actuated to move the inner catheter 110 proximally relative to the outer catheter 116, transitioning the anchor 200 to an expanded, deployed state within the target vessel. At step 714, the transducer 114 may be actuated to emit energy, e.g., ultrasonic energy, into the target vessel to reduce neural activity of nerves surrounding / innervating the target vessel. For example, the transducer 114 may be actuated to emit energy according to a predetermined ablation regimen. The predetermined ablation regimen may be selected, for example, to prevent over-exposure and / or over-ablation of the vessel. For example, a predetermined ablation regimen may include predetermined non-ablative periods between predetermined ablation periods during which the transducer 114 emits energy within a blood vessel, during which the transducer 114 does not emit energy, or alternatively emits a reduced amount of energy. For example, a predetermined ablation regimen may cause the transducer 114 to emit energy for, e.g., 10 seconds, then not emit energy for, e.g., 5 seconds, before emitting energy for another 10 seconds, etc.

[0170] The transducer 114 may be operatively coupled to a generator to provide power to the transducer 114, for example, via the conductive portion 602 and the cable 600. The generator may be programmed with one or more control loops to ensure safe ablation by the transducer 114. During ultrasonic vibration / ablation, the transducer dissipates energy that was not converted to acoustic energy in the Joule effect, thereby increasing the transducer temperature. Heating of the transducer surface may vary depending on the transducer structure depending on its individual efficiency. Energy in less efficient structures will dissipate in the Joule effect, exposing the blood flow across the transducer to higher temperatures. The blood flow across the transducer acts as a natural coolant for the transducer, for example, because the anchor 200 is non-occlusive; however, if the blood is heated above a given temperature threshold due to the transducer temperature, the fibrogen in the blood may be denatured, leading to dangerous blood clots. The transducer temperature is a function / proportional to the power applied to it, and therefore a control loop may be implemented by the generator adapting the power delivery to a temperature target when a temperature threshold is exceeded. The control loop may also take into account temperature fluctuations due to other factors such as pulsatile blood flow.

[0171] As shown in FIG. 13, monitoring the temperature allows the generator to stop energy delivery if the temperature threshold is exceeded for a predetermined period of time, e.g., for a maximum duration above the threshold. For example, if the transducer temperature, e.g., as measured via a thermocouple 604 coupled to the generator, is below the temperature threshold, the generator may provide an amount of power corresponding to the amount requested by the user / catheter system 100. Once the temperature threshold is exceeded, a control loop adapts the power to prevent the transducer temperature from exceeding the target temperature. If the transducer temperature exceeds a safety threshold, e.g., for more than 2 seconds, the generator may pause power delivery to the transducer 114. As an example, the temperature threshold may be defined as 50° C. to 56° C., and the acceptable time above the threshold may be defined as 0 to 4 seconds.

[0172] In addition, anatomical airway structures adjacent to the transducer 114 may reflect acoustic energy back to the transducer 114 during the ablation procedure. The transducer 114 may convert the reflected acoustic energy into electrical energy, which may be measured by the generator. Thus, the electrical energy measured by the generator will be higher than if the airway were not present. Thus, the generator may detect the presence of an airway structure based on the increased electrical energy converted by the transducer 114, which indicates the level of acoustic energy reflected from the adjacent airway structure, and the control loop may be adjusted to shut off the ultrasonic vibrations in response to detection of a nearby airway structure.

[0173] In contrast to nerves located in the adventitia of the pulmonary artery vessel, the transducer is exposed to the bloodstream, which is an excellent coolant. As a result, the temperature gradient when the pulse is stopped is greater in the transducer than in the tissue. The use of duty cycles in the transducer electrical source to control the transducer temperature with limited effect on the temperature rise at the lesion site can maximize the output power without proportionally increasing the off time of the overall pulse duration.

[0174] Additionally, to increase the thermal energy dissipation of the transducer, a heat sink may be added to the proximal or distal end of the transducer. For example, the heat sink may be 1 cm 2 ~3cm 2 Alternatively, the proximal support frame may be connected to an anchor frame, formed from Nitinol or stainless steel, to spread the transducer thermal energy over the entire surface of the anchor, which may be less than 5 cm in contact with the blood flow. 2 ~30cm 2 can represent the surface area of

[0175] In step 718, upon completion of the ablation therapy, the handle 300 may be actuated to re-insert the anchor 200 as described above, and the catheter system 100 may be removed from the patient. In step 720, the guidewire and introducer may be withdrawn from the patient, and the entry site, e.g., the venipuncture, may be closed.

[0176] Figure 8 diagrammatically illustrates the general anatomy of the heart, including the pulmonary artery, and the catheter system 100. The access route illustrated in Figure 8 is one example of many possible access routes for use with the catheter system 100. As shown in Figure 8, an anchor 200 may be deployed within the left pulmonary artery LPA to anchor and center the transducer 114 within the LPA. The anchor 200 and transducer 114 are operably coupled to a handle 300 external to the patient via the elongated shaft 101 of the catheter system 100.

[0177] The elongated shaft 101 is generally advanced through the vascular system and the heart to a target location within the vascular system. As shown in FIG. 8, the elongated shaft 101 may be advanced through an access point in a peripheral vessel, such as the right femoral vein RFV, into the inferior vena cava IVC, through the right atrium RA of the heart H, into the right ventricle RV, and then through the pulmonary trunk PT to the left pulmonary artery LPA. Other anatomical structures labeled in FIG. 8 include the right pulmonary artery RPA, branch vessels BV, the superior vena cava SVC, and the left femoral artery LFA. Alternatively, the elongated shaft 101 may be advanced through an access point in the LFV, into the inferior vena cava IVC, through the right atrium RA of the heart H, into the right ventricle RV, and then through the pulmonary trunk PT to the left pulmonary artery LPA. Thus, the elongated shaft 101 may have a length of about 100 cm to about 150 cm (eg, about 100 cm, about 110 cm, about 120 cm, about 130 cm, about 140 cm, about 150 cm, and ranges between such values).

[0178] Alternatively, the elongated shaft 101 may be advanced through an access point in the jugular vein, ulnar vein, etc., into the SVC, through the right atrium RA of the heart H, into the right ventricle RV, and then through the pulmonary trunk PT into the left pulmonary artery LPA. Thus, the elongated shaft 101 may have a length of about 60 cm to about 120 cm (e.g., about 60 cm, about 75 cm, about 90 cm, about 105 cm, about 120 cm, and ranges between such values).

[0179] The target location may be any of several locations, for example, the pulmonary artery trunk PT, the left pulmonary artery LPA, the right pulmonary artery RPA, any of the branch vessels BV, the ostium of the left pulmonary artery LPA and / or the right pulmonary artery RPA, and / or the like. Additionally, different access methods may be used and the pulmonary vein or other pulmonary venous vasculature may be the target location. Additional access routes and potential targets are described in further detail herein.

[0180] Once at the target site, the transducer 114 can be activated to block, e.g., neuromodulate, the nerves surrounding the left, right, and / or main pulmonary arteries. Neuromodulation may be accomplished (e.g., via ablation, denervation, which may or may not be reversible, stimulation, etc.) using, for example, acoustic energy (e.g., ultrasound), microwave energy, radio frequency (RF) energy, thermal energy, electrical energy, infrared energy, laser energy, phototherapy, plasma energy, ionization energy, mechanical energy, cryoablation, chemical energy, pulsed field electroporation, combinations thereof, and the like.

[0181] During the dilatation of the blood vessel, pressure measurements within the blood vessel may be analyzed, for example, via a catheter system described herein, to confirm successful reduction of neural activity of the nerve surrounding the target blood vessel. Specifically, when a blood vessel having an active nerve is dilated, for example, by applying sufficient force to the inner wall of the blood vessel, baroreceptors within the blood vessel may be stimulated, thereby causing a corresponding increase in pressure within the blood vessel. However, data shows that when the neural activity of the nerve surrounding the blood vessel is reduced / inactivated, dilatation of the blood vessel either does not result in a corresponding increase in pressure within the blood vessel, or results in a much smaller increase in pressure within the blood vessel. Thus, by comparing the pressure gradient within the blood vessel during the dilatation of the blood vessel before and after the ablation procedure, successful reduction of neural activity of the nerve surrounding the blood vessel may be confirmed.

[0182] Referring now to FIG. 9, a method 900 for verifying a reduction in neural activity of a nerve is provided. In step 902, a first pressure information may be measured in a target vessel, e.g., a pulmonary artery, at a first time. For example, the pressure may be measured via one or more sensors or small transducers, e.g., FFR wires, integrated with the catheter system 100, e.g., proximal and / or distal to the transducer 114, or separate from the catheter system 100. Additionally or alternatively, the pressure may be measured via a commercially available transformer coupled to the lumen of the elongated shaft 101 or a transformer inserted into the lumen of the elongated shaft 101. The pressure sensor / transducer may be operably coupled to a controller of the catheter system 100 to record and analyze the pressure measurements. The first pressure information may indicate a pre-ablation baseline pressure in the vessel.

[0183] In step 904, a first force may be applied to the inner wall of the target vessel at a second time to open the vessel, thereby stimulating baroreceptors in the vessel wall. For example, the first force may be applied via an expansion mechanism. The expansion mechanism may be an expandable member, e.g., an expandable cage, that may be actuated to transition between a collapsed configuration and an expanded configuration, the expandable member applying a sufficient force to the inner wall of the vessel to open the vessel. Preferably, the expandable member does not occlude the vessel in the expanded configuration. Alternatively, the expandable member may be a balloon that is configured to be inflated to open the vessel. The expandable member may be disposed on a catheter separate from the elongated shaft 101 of the catheter system 100, or alternatively, the expandable member may be disposed on a distal region 104 of the catheter system 100, for example, proximal and / or distal to the transducer 114. In some embodiments, the anchor 200 may be used as an expansion mechanism such that the anchor 200 is expanded, for example, via the inner catheter 110 and the outer catheter 116, to a diameter greater than the diameter of the inner wall of the blood vessel, thereby expanding the blood vessel.

[0184] Alternatively, the expansion mechanism may be a catheter shaft that can be actuated to form a bend and thereby apply sufficient force to the inner wall of the blood vessel to expand the blood vessel. For example, the catheter shaft may be actuated by a pull wire that, when pulled proximally via actuation at the handle 300, causes the catheter shaft to bend and apply a force at the bend to the inner wall of the blood vessel. The bendable catheter shaft may be separate from the elongated shaft 101 of the catheter system 100, or alternatively, the bendable catheter shaft may be integrated with the elongated shaft 101, for example, the elongated shaft 101 may be configured to be actuated to form a bend and thereby apply a force to the inner wall of the blood vessel.

[0185] In step 906, second pressure information may be measured within the target vessel while the first force is applied to the interior wall of the vessel. The second pressure information may be indicative of a first pressure gradient between the pressure within the vessel while the first force is applied to the interior wall, opening the vessel, and a pre-opening pressure within the vessel that is associated with the first pressure information. The opening mechanism may then be actuated to cease application of the force to the interior wall of the vessel.

[0186] In step 908, an ablation device, e.g., transducer 114, may be activated to emit energy, e.g., ultrasonic energy, within the vessel at a third time to ablate nerves surrounding the vessel, e.g., as described above with respect to method 700. For example, anchor 200 may be deployed prior to ablation to center transducer 114 within the vessel. Once the ablation procedure is completed during the emission of energy, or once the ablation procedure is otherwise assumed to be completed, in step 910, a second force may be applied to the inner wall of the target vessel at a fourth time, e.g., via a dilation mechanism, to dilate the vessel, thereby stimulating baroreceptors within the vessel wall. In some embodiments, the pressure gradient is monitored in real time, and the dilation force is continuously applied and pressure is continuously measured during the emission of energy to determine when the ablation procedure has sufficiently reduced neural activity, thereby pausing the energy emission. Preferably, the same expansion mechanism can be used to apply the first and second forces to the inner wall of the vessel. Furthermore, the same amount of force is preferably applied during the first and second vessel expansions.

[0187] In step 912, third pressure information may be measured within the target vessel while the second force is applied to the interior wall of the vessel. The third pressure information may be indicative of a second pressure gradient between the pressure within the vessel while the second force is applied to the interior wall, opening the vessel, and a pre-opening pressure within the vessel, which is associated with the first pressure information. The opening mechanism may then be actuated to cease application of the force to the interior wall of the vessel.

[0188] In step 914, the controller of the catheter system 100 may compare the second pressure information with the third pressure information to determine whether the emitted energy has reduced the neural activity of the nerves surrounding the blood vessel. Additionally or alternatively, both the second and third pressure information may be displayed on the display for the user to manually compare the second and third pressure information to determine whether the reduction in the neural activity of the nerves surrounding the blood vessel has been successful. Thus, the success of the ablation therapy may be measured by a substantial reduction in neural activity or a complete inactivation of the nerve, as indicated by a comparison of the second and third pressure information. For example, if the comparison of the second and third pressure information indicates that the second pressure gradient is above a predetermined threshold and less than the first pressure gradient, it may be determined that the emitted energy has successfully reduced the neural activity of the nerves surrounding the blood vessel. Furthermore, if the second pressure gradient is zero, e.g., post-ablation dilatation has not resulted in any increase in pressure in the blood vessel, it may be determined that the emitted energy has successfully reduced the neural activity of the nerves surrounding the blood vessel.

[0189] If the comparison of the second and third pressure information indicates that the neural activity of the nerve is not sufficiently reduced, e.g., the second pressure gradient is not above a predetermined threshold and less than the first pressure gradient, the above steps, e.g., steps 908-914, may be repeated. For example, the transducer 114 may be redeployed, if not already deployed, to emit additional energy within the target vessel. The target vessel may then be opened by applying a third force to an inner wall of the target vessel, and fourth pressure information may be measured within the target vessel while the third force is applied to the inner wall of the vessel, such that the fourth pressure information may indicate a third pressure gradient between the pressure within the vessel while the third force is applied to the inner wall, opening the vessel, and a pre-opening pressure within the vessel, which is associated with the first pressure information. The fourth pressure information may then be compared to the third pressure information and / or the second pressure information to confirm that the neural activity of the nerve surrounding the target vessel has been sufficiently reduced. The above method steps may be repeated until confirmation is received that neural activity in the nerve surrounding the target vessel has been sufficiently reduced.

[0190] To minimize the thickness of the outer diameter of the transducer, e.g., transducer 114, a conductive ring (e.g., copper) or tape may be used to extend the outer electrode connections and solder from the inner diameter of the transducer assembly. To optimize the radiation of the piezoelectric element of the transducer 114 and reduce the mass loading effect due to the outer connections, the copper ring or tape may cover the entire circumference of the outer electrode of the transducer 114. Furthermore, to control the directivity or uniformity of the emitted energy, e.g., acoustic beam, the inner diameter connections of the transducer assembly may be made from one or several connections spread over the inner electrode. Each solder spot over the inner electrode may generate a mass load and change the radiation pattern of the transducer. For example, a wide or thick solder spot may narrow the directivity to 50% from the maximum intensity at -6 dB, as shown in FIG. 10, while a thin solder spot may lead to 100% directivity from the maximum intensity at -6 dB.

[0191] In addition, the transducer 114 may be covered with a very thin sleeve, e.g., not meant to be a biocompatible material, to cover the piezoelectric surface, to provide electrical insulation for patient protection, and to define the thickness of the transducer cover depending on the drive voltage amplitude and material dielectric strength. The sleeve may also be thin enough to allow for thermal dissipation of the transducer in the bloodstream during ultrasonic vibration.

[0192] 11, an alternative distal region of a catheter system is provided. Distal region 104' may be constructed similarly to distal region 104, with like components having like primed reference numbers. However, distal region 104' differs from distal region 104 in that distal region 104' may include multiple guidewire ports, e.g., guidewire port 1102 disposed on the distal region of outer catheter 116' and guidewire port 1104 disposed on the distal region of sheath distal region 118b'. In addition, the inner catheter 110' may include a guidewire port (not shown) such that the proximal end of the guidewire may enter the lumen of the inner catheter 110' via the tip 111' and be fed through the guidewire port disposed on the inner catheter 110', through the guidewire port 1102, and through the guidewire port 1104, such that the guidewire may extend along the exterior of the elongated shaft of the catheter system as the distal region 104' is advanced over the guidewire to a target location within the blood vessel. Thus, the inner catheter 110' does not need to have a guidewire lumen extending through its entire length, which would allow the inner catheter 110' to have a smaller profile proximal to its guidewire port. Thus, the profile of all components of the elongated shaft proximal to the distal region 104' may be significantly reduced, reducing the stiffness of the elongated shaft and thus facilitating navigation and preventing cardiac compression during the procedure.

[0193] As described above, the anchor 200 may be laser cut, for example, from a metal hypotube. In some embodiments, the anchor may undergo an extensive electropolishing process to round all of the edges of its multiple struts, thereby making the anchor safe for contacting the patient anatomy during catheter delivery and / or during ablation site to ablation site transition. Thus, in this configuration, the catheter system would not require a sheath to be placed over the anchor during delivery and ablation site to ablation site transition. Furthermore, since a sheath would not be required, a separation sleeve may also not be required, since neither the transducer nor the anchor would need to be stabilized while the sheath is moved relative to the transducer and anchor. Thus, the profile of the elongated shaft of the catheter system would be significantly reduced, for example, by the thickness of the sheath and separation sleeve. In addition, the profile of the tip at the distal end of the inner catheter may also be reduced. Because there may be no need for a sheath or separate sleeve, the corresponding hub in the handle may be eliminated, thereby also reducing the profile of the handle.

[0194] Furthermore, since the profile of the distal region of the catheter system dictates the size of the puncture required in the patient, for example at a venous access point, a distal region having a smaller profile will be more favorable for healing and reduce the risk of infection, for example when the puncture is made in the groin area. To reduce the profile of the distal region formed by the transducer, anchor, and sheath, a frame may be positioned distal to the transducer in both the collapsed delivery state and the expanded deployed state. For example, the proximal end of the anchor may be coupled to the distal end of the transducer shaft, which extends through the transducer and the tip of the inner catheter.

[0195] 12, an alternative exemplary handle is provided. Handle 300' may be constructed similarly to handle 300, with similar components having similar primed reference numbers. Handle 300' differs from handle 300 in that handle 300' includes a pusher 1200. Pusher 1200 is operably coupled to a transducer in a distal region of the catheter system and configured to be actuated to transitionally move the transducer relative to the frame. Thus, in this configuration, the transducer may be moved longitudinally relative to the outer and inner catheters. Thus, the transducer may be coupled to a transducer catheter that is slidably disposed within the outer catheter such that the proximal end of the anchor remains coupled to the outer catheter. Additionally, the transducer catheter may have a lumen sized and shaped to slidably receive the transducer shaft therein, and instead of the outer catheter being sealed to the transducer shaft, the transducer catheter may be sealed to the transducer shaft, forming a fluidly sealed cavity between the transducer shaft and the transducer catheter.

[0196] Thus, the pusher 1200 may be operably coupled to a transducer assembly, e.g., a transducer shaft, transducer, and transducer catheter, such that actuation of the pusher 1200 causes translational movement of the transducer shaft, transducer, and transducer catheter relative to the anchor. Thus, the transducer assembly may move relative to the anchor to perform multiple ablations without collapsing and redeploying the anchor, as described in further detail below with respect to Figures 22A and 22B. As further shown in Figure 12, an inner catheter hub 308', operably coupled to the inner catheter, and an outer catheter hub 310', operably coupled to the outer catheter, may both be operably coupled to the knob 304' such that actuation of the knob 304' causes relative movement of the inner and outer catheters in equal and opposite directions.

[0197] It is noteworthy that denervation around the pulmonary artery may interfere with several adjacent anatomical structures, such as the aorta, vena cava, pulmonary veins, phrenic nerve, recurrent laryngeal nerve, trachea, bronchi, and lungs. The aorta, vena cava, and pulmonary veins are protected by blood flowing within these vessels, and thus heat generated by absorption of the acoustic beam by the vessel walls is dissipated by blood flow inside these vessels. However, this is not true for non-target nerves, such as the phrenic and recurrent laryngeal nerves, which are not in the vicinity of vascularized vessels, or the airways, such as the trachea and bronchi, which are filled with air and cause reflection of a large portion of the incident acoustic beam, thereby exposing the target vessels to the incident energy up to twice.

[0198] To ensure that non-targeted nerves are not damaged by the acoustic beam during ultrasound vibration, the transducer may be designed to be non-uniform, as described in more detail below with respect to Figures 19B-19D. For example, the transducer may be designed so that 50%-75% of the circumference of the transducer is non-uniform, e.g., 15-33 W / cm. 2 14, an angle of -180° to +45° is sufficient exposure to generate a lesion (zone 1402) while the remaining 50% to 25% are configured to emit half of this intensity. As shown in FIG. 14, an angle of -180° to +45° is sufficient exposure to generate a lesion (zone 1402) using direct targeting, while angles of +45° to +180° are not sufficiently exposed to generate a lesion unless they are reflected on the airway (zone 1404). The portion of the energy emitted at the reduced intensity may be referred to herein as a "dead zone." The dead zone may be angled / directed towards an anatomical structure sought to be avoided during the ablation procedure.

[0199] The method requires that the orientation of the transducer be carefully considered during the procedure. Under fluoroscopy, radiopaque marker bands may be placed on the transducer 114 to allow the user to determine the location of the dead zone. The radiopaque markers may have an axially asymmetric shape, such as an "L" or a "P", so that the operator can easily discern the orientation of the transducer. For example, one or more radiopaque markers may be placed in two perpendicular planes, respectively, relative to the positioning.

[0200] 15, an alternative exemplary catheter system is provided. The elongated shaft 101'' may be constructed similarly to the elongated shaft 101, with similar components having similar double primed reference numbers. However, the elongated shaft 101'' differs from the elongated shaft 101 in that the elongated shaft 101'' may include a torque shaft 1500. The torque shaft 1500 may be formed, for example, from a multifilar wire. A proximal region of the torque shaft 1500 may be operably coupled to a handle of the catheter system, and a distal region of the torque shaft 1500 may be coupled to the transducer 114'' such that the torque shaft 1500 may be actuated to rotate the transducer 114'' via the handle. Thus, the torque shaft 1500 may have a lumen sized and shaped to slidably receive the inner catheter 110'' therein, and may be disposed within the outer catheter 116''. Because the inner catheter 110'' is fixed to the tip 111'', the inner catheter 110'' can remain stationary as the torque shaft 1500 causes rotation of the transducer 114''. Preferably, rotation of the transducer 114'' is limited to 180° in both directions from a neutral configuration to avoid wrapping the cables / electrical wires around the torque shaft 1500.

[0201] 16, another alternative exemplary catheter system is provided. The distal region 104''' of the catheter system may be constructed similarly to the distal region 104, with similar components having similar triple primed reference numbers. However, the distal region 104''' differs from the distal region 104 in that the distal region 104''' may include one or more intravascular imaging transducers, such as an intravascular ultrasound (IVUS) transducer. The IVUS transducer 1600 is configured to provide intravascular imaging and enable a user to detect adjacent airways or other sensitive anatomical structures within the field of view of the IVUS transducer 1600, such as the trachea and bronchial airways, laryngeal and phrenic nerves, pericardium, aorta, etc. The IVUS transducer 1600 may be a solid-state ultrasound imaging transducer or a rotational piezoelectric ultrasound imaging transducer.

[0202] The IVUS transducer 1600 may generate data that is used to measure the distance between the pulmonary artery and the adjacent airway. The data may illustrate the airway as a lumen, but may also illustrate a "blind spot" reflected from the cartilage. Thus, the transducer 114''' may be rotated as described above with respect to FIG. 15 to align the blind spot with the dead zone of the energy emission as described above with respect to FIG. 14 to avoid ablating the airway, or otherwise direct the energy emission away from the airway. As shown in FIG. 16, a first IVUS transducer may be positioned on the inner catheter 110'''' between the distal end of the anchor 200''' and the tip 111''', a second IVUS transducer may be positioned on the outer catheter 116''' between transducer 114'''' and the proximal end of the anchor 200''', and / or a third IVUS transducer may be positioned on the outer catheter 116''' proximal to the proximal end of the anchor 200'''. As will be understood by one of ordinary skill in the art, more or fewer IVUS transducers may be integrated into the distal region 104''' of the catheter system or positioned at different locations along the distal region 104'''' than those illustrated in FIG.

[0203] As adjacent sensitive anatomical structures may be imaged via the IVUS transducer 1600, it is important for the user to know the direction in which the transducer's dead zone is currently pointing so that the transducer's dead zone may be oriented to avoid the anatomical structures. As shown in FIG. 17A, a shield 1702, e.g., a strip of metal or a section of cut metal hypotube, may be placed over the IVUS transducer 1600, thereby masking a portion of the image generated via the IVUS transducer 1600. Thus, the shield 1702 may be oriented, e.g., as described above with respect to FIG. 15, to align the shield 1702 with the dead zone of the transducer 114'''.

[0204] As shown in FIG. 17B, the IVUS transducer 1600 may provide imaging of the airway 1706 within a field of view 1708. Rotating the IVUS transducer 1600 and transducer 114''' will rotate the blind spot on the image as well as the dead zone of the transducer 114'''. Thus, the blind spot and the dead zone may be aligned with the airway 1706 to avoid ablation of the airway 1706. In this configuration, both the IVUS transducer 1600 and transducer 114''' are positioned on a torque shaft as described above with respect to FIG. 15.

[0205] 18, another alternative exemplary catheter system is provided. The distal region 104'''' of the catheter system may be constructed similarly to the distal region 104, with similar components having similar triple primed reference numbers. However, the distal region 104'''' differs from the distal region 104 in that the distal region 104'''' includes one or more pacing electrodes 1800 disposed thereon. As shown in FIG. 18, the pacing electrodes 1800 may be disposed on the anchor 200'''' such that the pacing electrodes 1800 may contact the inner wall of a blood vessel. Additionally or alternatively, the pacing electrodes 1800 may be disposed on one or more expandable members proximal and / or distal to the anchor 200''''. The phrenic nerve runs along the main pulmonary artery and controls diaphragmatic movements, e.g., hiccups. The pacing electrode 1800 may prevent damage to the phrenic nerve by pacing the blood vessel, detecting the location of the phrenic nerve, and / or cutting off the ablation energy by the generator's control loop in response to detecting the phrenic nerve. For example, the pacing electrode 1800 may pace the blood vessel prior to ablation to determine whether the phrenic nerve is within the target ablation location in the blood vessel. This may be indicated by a physiological response from the patient, e.g., a hiccup, corresponding to the pacing pulse of the electrode 1800 if the phrenic nerve is located around the blood vessel being paced. The physiological response may be measured by the clinician, e.g., by palpating the patient's diaphragm during pacing. Thus, this portion of the blood vessel may be avoided (not ablated) to avoid damaging the phrenic nerve. Additionally, the pacing electrode 1800 may pace the blood vessel during ablation with the transducer 114'''' and detect any abnormalities during pacing that may be indicative of damage to the phrenic nerve. For example, if the phrenic nerve is detected via pacing by the pacing electrode 1800, the clinician may palpate a physiological response by the patient during the ablation procedure such that changes in frequency and / or intensity of the physiological response may be indicative of damage to the phrenic nerve.Thus, the user may stop the ablation if such a change in physiological response due to pacing is detected during the ablation. As will be understood by one skilled in the art, more or less than four pacing electrodes may be integrated with the distal region 104'''', as shown in FIG.

[0206] 19A illustrates an exemplary transducer 1900. The transducer 1900 may be positioned at or near a distal portion of a catheter system (e.g., catheter system 100). The transducer 1900 may be separate from any anchor (e.g., as described herein). The transducer 1900 may be coupled to a shaft (e.g., elongated shaft 101). The transducer 1900 may include a hole 1902 extending therethrough, for example, for coupling to a wire or tube of a catheter. A guidewire or sensor wire may extend through the hole 1902. In some embodiments, the transducer 1900 is an arc-shaped ultrasound transducer that includes a piezoelectric element.

[0207] For example, the outer diameter of the transducers described herein, including transducer 1900, may be about 3 mm to about 10 mm (e.g., about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, and ranges between such values). The transducer may have a length of about 5 mm to about 30 mm (e.g., about 5 mm, about 10 mm, about 15 mm, about 20 mm, about 25 mm, about 30 mm, and ranges between such values). A longer and / or thicker transducer may generally provide more power. A shorter and / or thinner transducer may be easier to navigate through the vasculature. A thinner transducer may be used in conjunction with a smaller incision, which may reduce scar size, infection site size, and / or healing time. The ratio between the diameter of the transducer and the length of the transducer may be from about 1 / 20 to about 2 / 1 (e.g., about 1 / 20, about 1 / 15, about 1 / 10, about 1 / 5, about 1 / 3, about 1 / 1, about 3 / 2, about 2 / 1, and ranges between such values).

[0208] FIG. 19B illustrates another exemplary transducer 1910. The transducer 1910 may comprise a first half cylinder 1912a and a second half cylinder 1912b. The first half cylinder 1912a and the second half cylinder 1912b may be joined to form a cylindrical shape. The first half cylinder 1912a may be activated for ablation while the second half cylinder 1912b is inactive. Partial activation can provide partial circumferential ablation, for example, to protect sensitive structures within the area around the second half cylinder 1912b. The first half cylinder 1912a may be activated for ablation and the second half cylinder 1912b may also be activated for ablation. Coordinated activation can provide full circumferential ablation, for example, to treat tissue all around a vessel. Circumferential ablation, such as may be provided by the transducer assemblies provided herein, can reduce or eliminate rotation at the ablation site. In some embodiments, the transducer 1910 is an arc-shaped ultrasound transducer that includes a piezoelectric element.

[0209] FIG. 19C illustrates another example transducer 1920. The transducer 1920 may comprise multiple angle or wedge-shaped arcuate regions 1922. Although eight angle regions 1922 are depicted in FIG. 19C, any number of regions may be used (e.g., two regions (e.g., as shown in FIG. 19B), three regions, four regions, five regions, six regions, seven regions, eight regions (e.g., as shown in FIG. 19C), nine regions, ten regions, eleven regions, twelve regions, and ranges of these values). The regions 1922 may all be identical, e.g., including the same material, shape, dimensions, and / or equivalents. Alternatively, at least one of the regions 1922 may differ from at least one other of the regions 1922. For example, the differences may include materials, shapes, dimensions, and / or equivalents.

[0210] In another embodiment, the transducer may be asymmetrically divided into two independently actuatable regions, e.g., the circumference of the transducer may be divided between 10-90%, 15-85% or 25-75%, etc. For example, when divided between 10-90%, one region will occupy 10% of the circumference of the transducer while the other region will occupy 90% of the circumference of the transducer. Thus, the 90% region may be actuated to emit energy during an ablation procedure while the 10% region will not emit energy, thereby forming a "dead zone" of the transducer where no energy is emitted. As explained above, the transducer may be rotated via a torque shaft such that the dead zone may be angled / directed towards sensitive anatomical structures to avoid damaging nearby anatomical structures.

[0211] The angular regions 1922 may be activated through multiple wires 1926, each connected to an ultrasound system and one or more of the regions 1922. In some embodiments, a user may determine the regions 1922 to activate during ablation. For example, the angular regions 1922 in FIG. 19C that are shaded are activated for ablation, while the non-shaded angular regions are not activated for ablation. The regions 1922 facing sensitive structures may not be activated to spare those sensitive structures from being ablated. A larger number of regions 1922 may provide more activation flexibility in some such embodiments. A smaller number of regions 1922 may provide lower manufacturing complexity. In some embodiments, each angular region 1922 includes a spring contact pad that may allow power to flow through the disk when the disk is across the region 1922.

[0212] FIG. 19D illustrates an example transducer connection implementation in which stacked disks 1924, which rotate on the edge of the transducer 1920, can electrically connect to or disconnect from the angular regions 1922. As shown in FIG. 19D, the angular regions 1922, which are shaded, can be electrically connected through the stacked disks 1924 and collectively activated for ablation. The angular regions 1922 that are not connected through the stacked disks 1924 cannot be activated for ablation. In some embodiments, the stacked disks 1924 may be rotated independently through push and pull wires. In some embodiments, the stacked disks 1924 comprise a single half disk 1924, two stacked half disks 1924, a single two-thirds disk 1924, a single three-quarters disk 1924, etc. The disks 1924 can provide an ablation profile that inhibits or prevents ablation in areas where sensitive structures or other structures that are not desired to be ablated are located. The rotation of the disk 1924 can be controlled from the proximal side of the catheter, for example, through a wheel that rotates the shaft with appropriate torque transmission. Two radiopaque symbols located on the actuation shaft can inform the operator about the positioning of the disk 1924 and thus about the ablation profile that is or will be created.

[0213] Referring again to FIG. 8 , the elongated shaft 101 may need to navigate a generally tortuous anatomy, including, for example, a U-turn in the right ventricle immediately followed by a right turn into the right atrium. If any portion of the elongated shaft 101 is too stiff or not flexible enough to make such a turn, the distal region 104 may not be able to be delivered to the target location. FIG. 19E diagrammatically illustrates an exemplary transducer 1950 comprising multiple longitudinal segments 1952. The transducer 1950 may comprise any suitable quantity of longitudinal segments 1952 (e.g., two segments, three segments, four segments (e.g., as shown in FIG. 19E ), five segments, six segments, and ranges between such quantities). More segments 1952 are also possible. The segments 1952 can be abutting or spaced apart by a distance. The segments 1952 may be spaced apart during navigation, and then an actuator (e.g., controlling a pull wire and / or push rod) may abut the segments during ablation. The transducer 1950 may facilitate bending of the distal portion of the catheter during navigation to the target location, as the catheter is able to bend between the segments 1952. In some embodiments, the segments 1952 may provide electronic focusing of the ultrasound beam using phase wave generation. The segments 1952 may be partially activated, for example, similar to the semi-cylindrical segments 1912a, 1912b and / or angular regions 1922 described herein. For example, one, some, or all of the segments 1952 may be activated for ablation, depending on where the nerve targeted for ablation is located and where sensitive structures may be located.

[0214] 20A-20D illustrate exemplary outer surface shapes of exemplary transducers. FIG. 20A is an end or cross-sectional view of a transducer 2020 having a rounded outer shape 2022. The outer surface of the transducer 2020 need not be a perfect circle. For example, the transducer 2020 may be oval, elliptical, egg-shaped, etc. A transducer 2020 having a rounded or arcuate outer surface shape can provide an ultrasound beam that projects in all directions, for example, as shown diagrammatically in FIG. 20A. An ultrasound beam that projects in all directions can allow ablation to occur around the entire area surrounding the vessel wall at the ablation site, which optionally reduces or eliminates rotation of the transducer 2020 since the entire circumferential area can be treated with one ablation. Using only one ablation can reduce procedure time. Reduced procedure time for a target location can be particularly important, for example, when multiple target locations (e.g., multiple locations within the RPA, LPA, and PT) are treated and / or when anchors are collapsed and then re-expanded between ablations.

[0215] 20B-20D illustrate additional exemplary outer shapes of transducers. FIG. 20B is an end view or cross-section of a transducer 2024 having an octagonal outer shape. FIG. 20C is an end view or cross-section of a transducer 2026 having a decagonal outer shape. FIG. 20D is an end view or cross-section of a transducer 2028 having a dodecagonal outer shape. Transducers having any number of polygonal sides, preferably more than 5 and less than 32, are also possible. Although not a perfect circle, a more numerous polygonal outer shape can function similarly to a rounded outer shape in that the projected ultrasound beam is in all directions from the transducer, producing a large coverage. The transducer does not have an overall flat shape. For example, the transducer is a two-sided, non-flat triangle, square, trapezoid, parallelogram, or rectangle. Flat geometry transducers such as those listed herein may not be able to provide a complete projection of the ultrasound energy and / or may require rotating the transducer to ablate all of the targeted nerves.

[0216] Transducers 2022, 2024, 2026, 2028 may include multiple half-piece or wedge-shaped regions (e.g., as described with respect to Figures 19B and / or 19C), multiple longitudinal segments (e.g., as described with respect to Figure 19E), and such regions and / or segments may be individually, partially, and / or collectively activated as desired.

[0217] Any one of the transducers described herein or other transducers may be optionally coupled to a lens to focus or out-focus the ultrasonic energy. For example, energy from a cylindrical transducer may be focused by a lens to produce a toroidal or doughnut-shaped treatment area around the transducer. Other shapes are also possible (e.g., spherical, elliptical, ovoid, arcuate, hemispherical, cigar-shaped, disk-shaped, plate-shaped, bulging versions thereof, etc.). The transducer may be acoustically coupled to the lens using a piezoelectric material. The combination of the transducer and lens may be referred to as a transducer assembly, which may include a coupling material. In certain embodiments where the device does not include a lens, references to the transducer assembly herein may refer to the transducer itself, and optionally associated components such as conductor wires, materials coupling the transducer to the shaft, etc. The focal length may be affected by the lens geometry, the energy applied to the transducer, the efficiency of the components and / or the assembly, and / or other parameters. In some embodiments, the efficiency of the assembly is tested by the manufacturer or a testing laboratory, and the known efficiency is used during treatment.

[0218] FIG. 21A illustrates an exemplary Fresnel lens 400. The lens 400 is acoustically coupled to the transducer. The Fresnel lens 400 comprises a plurality of prisms configured to redirect acoustic energy from the transducer such that the energy is generally focused in a common longitudinal area. The Fresnel lens can reduce the overall diameter of the catheter system, e.g., the catheter system 100 and / or a portion thereof (e.g., a distal portion) because the prisms can redirect the energy while maintaining a low profile (e.g., compared to a convex surface, which may have an increasing diameter toward the longitudinal edges). FIG. 21B diagrammatically illustrates an exemplary energy beam emanating from the prisms and longitudinally focusing and concentrating the acoustic energy into a smaller section 2102 around the transducer assembly. In practice, the section 2102 can be tissue surrounding a vessel in which the transducer is positioned. In some embodiments, for a 22 mm focal spot, measured radially outward from the center of the transducer, the lesion may be created by the energy pre-focal (e.g., approximately 1.5-5 mm from the vessel wall, depending on vessel diameter and other parameters). A larger amount of energy delivery and / or a longer delivery duration can increase the focal depth. A smaller amount of energy delivery and / or a shorter delivery duration can decrease the focal depth. The focal point of the energy does not need to be a very precise location or band. FIG. 21C illustrates an example portion of an energy application shape. A portion of the toroid area 2105 is illustrated. The energy application shape may be a full toroid, but for clarity is shown in FIG. 21C as only a portion of a toroid. In some embodiments, a partial toroid, as shown in FIG. 21C, may be created, for example, by activation of less than the entire transducer (e.g., one, two, or several wedges). The energy produced by the transducer may be absorbed, at least in part, by tissue within and / or surrounding the vessel, which can create a toroid ablation site 2105.Other energy application shapes are also possible (eg, spherical, elliptical, oval, arcuate, hemispherical, cigar-shaped, disk-shaped, plate-shaped, inflated versions thereof, etc.).

[0219] The lens preferably comprises one or more materials that are acoustically conductive, good thermal conductors, good electrical insulators, and / or biocompatible. No material may possess all of these properties, and thus multiple layers may be used (e.g., the outermost layer may be biocompatible to protect the body from inner layers that are not biocompatible). In some embodiments, the lens comprises aluminum that has been anodized or otherwise treated to have a coating of aluminum oxide (alumina). Both aluminum and alumina are good thermal conductors, aluminum is acoustically conductive (e.g., the speed of sound through aluminum is about four times that through blood), and alumina is biocompatible and a good electrical insulator. In some embodiments, the lens comprises silicon dioxide. Silicon dioxide is a good thermal conductor and biocompatible, and may be suitably acoustically conductive, e.g., with some doping.

[0220] FIG. 21D illustrates an exemplary transducer assembly. The assembly includes another example of a lens 2110 coupled to a transducer (e.g., as described herein). The lens 2110 may be an ultrasonic lens. FIG. 21D is a cross-sectional view through a longitudinal axis L depicting a transducer assembly including a cylindrical transducer 2130 and an ultrasonic lens 2110. The lens 2110 has an inner cylindrical surface and an outer surface that is shaped with a concave profile. The lens 2110 is acoustically coupled to the transducer 2130. The transducer assembly also includes a piezoelectric element 2112. The lens 2110 can focus energy from the transducer 2130 (e.g., as described herein). Because the lens 2110 does not include multiple prisms, the lens 2110 can have a larger diameter than the Fresnel lens 400. Lens 2110 may be easier to manufacture than Fresnel lens 2100. Lens 2110 may be easier to clean with saline prior to insertion into the vasculature than Fresnel lens 2100.

[0221] The lens 2110 or Fresnel lens 2100 increases the surface area in contact with the blood inside the vessel, which can improve the transducer's ability to cool by acting as a heat sink. To act as a heat sink, the lens material is preferably a thermal conductor (e.g., aluminum, alumina, silicon dioxide). The multiple prisms of the Fresnel lens 2100 can act as fins for the heat sink. In some embodiments, the lens 2100, 2110 comprises a biocompatible layer 2114. The lens covers the piezoelectric material 2112 of the transducer 2130 and inhibits or prevents contact between the blood and the outer surface of the transducer. In some embodiments, the lens comprises an electrical insulator layer 2116. The insulator layer 2116 isolates the patient from the high voltage used to drive the transducer energy. The lens material may support dielectric properties to protect the patient from the high voltage.

[0222] The devices described herein may lack or be without a cooling system, which can advantageously significantly reduce device costs. For example, blood flow through the pulmonary artery may be sufficient to cool the transducer assembly. In contrast, a transducer assembly positioned in the renal artery may not be exposed to sufficient blood flow to provide sufficient cooling, and such devices may include a cooling system (e.g., a saline lumen pumped through the transducer before, during, and / or after ablation).

[0223] The size of the lens may depend, for example, at least in part, on the material and / or frequency (e.g., the natural frequency and / or the frequency applied from the ultrasound beam generator). Frequency adjustments may be made, for example, during calibration or setup of the transducer, and thus such adjustments do not need to be made during the procedure. Different frequencies may be used to ablate different depths outside the vessel. The material selected for the lens may affect the frequency required for ablation. For example, if an acoustically poor material such as glass is used, the lens will be thinner to account for losses caused by the acoustically poor material. For example, if the material used has good acoustic properties, the lens may be thinner. For example, for a 25 mm focal length at 3 MHz across a 4 mm outer diameter transducer, an aluminum lens (c=6,500 m / sec) may have a 5.4 mm outer diameter, while an epoxy lens (c=2,430 m / sec) may have a 7 mm outer diameter for the same focal length.

[0224] Each transducer and lens combination has an associated data sheet that characterizes the transducer assembly and accounts for the differences between transducer and lens combinations. Because the absorption of acoustic energy by tissue is a function of the frequency of the ultrasound beam, the transducer assembly should be carefully designed to meet the desired specifications. In one exemplary implementation, a 4 mm outer diameter transducer is coupled to a 5 mm outer diameter aluminum Fresnel lens with a 25 mm focal length for operation at 4.5 MHz. In another exemplary implementation, a 4 mm outer diameter transducer is coupled to a 6 mm outer diameter epoxy Fresnel lens with a 25 mm focal length for operation at 4.5 MHz. In another exemplary implementation, a 1.5 mm outer diameter transducer is coupled to a 2.15 mm outer diameter aluminum Fresnel lens with a 10 mm focal length for operation at 6 MHz. In another exemplary implementation, a 1.5 mm outer diameter transducer is coupled to a 2.8 mm outer diameter epoxy Fresnel lens with a 10 mm focal length for operation at 6 MHz. The catheter may include one or more irrigation ports to inhibit or prevent the introduction of bubbles inside the patient (eg, bubbles that may otherwise become trapped within the prisms of the Fresnel lens).

[0225] As explained above, during ablation, the transducer assembly (e.g., as described herein) may be anchored within the vessel, e.g., via anchor 200. If the transducer assembly is not anchored, it may float or rotate in the blood flow, especially in high blood flow such as in the pulmonary artery, which may cause highly unpredictable or at least blurry and inefficient ablation. Thus, the position of the transducer may be stabilized by the anchor.

[0226] The anchors described herein may be configured to preserve blood flow through the vessel, including when the anchor is in a deployed state. Methods including the anchor may include allowing blood to flow through the vessel when the anchor is in a deployed state. In some embodiments, the anchor does not include a balloon. For example, the prismatic edges of the lens (e.g., Fresnel lens 2100) may damage the balloon anchor. In some embodiments, the anchor is not occlusive and allows blood to continue to flow to downstream vessels and organs (e.g., lungs). For example, renal denervation devices including balloons are typically occlusive because they are capable of ceasing blood flow to the kidney without negative systemic effects. In some embodiments, devices configured for use in the pulmonary branch vessels (RPA and / or LPA) may include anchors that occlude blood flow to one lung at a time, since the other lung may be sufficient to oxygenate the blood for a short duration.

[0227] 22A illustrates an exemplary embodiment of an anchor 2200 comprising multiple struts 2204 in a collapsed or delivery state. The anchor 2200 is navigated into the vessel in the delivery or collapsed state. In some embodiments, the anchor 2200 may be covered with a sheath during delivery or at other times in the delivery state. The anchor 2200 is deployable toward a deployed state.

[0228] Figure 22B illustrates anchor 2200 in a deployed state. Depending on the diameter of the vessel, it may not be possible to achieve the delivery state shown in Figure 22B, however, expansion of anchor 2200 such that anchor 2200 is capable of maintaining a substantially constant position of transducer assembly 2201 within the vessel may be considered the deployed state. Ablation preferably occurs when anchor 2200 is in the deployed state, or not in the delivery state.

[0229] The struts 2204 may be cut (e.g., laser cut) from a hypotube or sheet, for example. Cutting the struts 2204 from a tube or sheet may provide for rapid and repeatable manufacturing, for example. In some embodiments, the struts 2204 are discrete wires. The wires may optionally not be cut from a tube or sheet, or may be cut from a tube or sheet in a manner that allows at least some of the struts 2204 to be discrete from the start (e.g., not directly bonded to another strut by the strut material). Using discrete wires may provide flexibility in determining the shape and configuration of the struts 2204. For example, the struts 2204 may comprise wires that are straight, twisted, flat, rounded, combinations thereof, etc. (e.g., as shown in FIGS. 22A-22D). The wire may have a polygonal cross-section (e.g., rectangular, square, diamond, trapezoidal, bulged versions thereof, etc.), rounded or arcuate cross-section (e.g., circular, oval, elliptical, etc.), combinations thereof, and the like.

[0230] The struts 2204 may be coupled (e.g., individually coupled) distally and proximally to the transducer assembly 2201 (e.g., glued, soldered, welded, not separated when cut from the tube or sheet, combinations thereof, and the like). As shown in FIG. 22A , a distal portion of the struts 2204 is coupled to a distal shaft 2202 and a proximal portion of the struts 2204 is coupled to a proximal shaft 2212. The distal shaft 2202 may comprise an atraumatic tip. The distal portion of the struts 2204 may be coupled to the distal shaft 2202 distal to the transducer assembly 2201. The proximal portion of the struts 2204 may be coupled to the proximal shaft 2212 proximal to the transducer assembly 2201. The transducer assembly 2201 may be substantially radially centered between the struts 2204 in the delivery state and / or the deployed state. The distal shaft 2202 is longitudinally movable relative to the proximal shaft 2212. Such longitudinal movement may be permitted during self-expansion of the anchor 2200 and / or may be used to expand the anchor 2200. As the struts 2204 recurve radially outward, the longitudinal distance between the distal portion of the struts 2204 and the proximal portion of the struts 2204 is reduced. The transducer assembly 2201 may be substantially radially centered between the struts 2204 in the delivery state and / or in the deployed state.

[0231] In some embodiments, the anchor 2200 is deployed by pushing the proximal and distal portions of the struts 2204 together (e.g., retracting the distal shaft 2202 proximally and / or advancing the proximal shaft 2212 distally), as shown in FIG. 22B, causing the struts 2204 to bend radially outward. In the deployed state, the struts 2204 expand to contact or adhere to the vessel wall. The anchor 2200 may maintain the longitudinal position of the transducer assembly 2201. This umbrella type deployment method may provide better control of the radial force being applied by the anchor 2200 to the vessel wall. If the movement is manual by the user's hand, for example, the user could feel when the struts 2204 contact the vessel wall and stop the expansion of the struts 2204 at the appropriate deployed state. If the movement is motorized, for example, a sensor may be used to measure the force and stop the movement upon reaching a certain force. To return to the delivery state, the struts 2204 are pulled apart (e.g., by advancing the distal shaft 2202 distally and / or retracting the proximal shaft 2212 proximally), causing the struts 2204 to collapse back to the delivery state. The anchor 2200 is configured to expand to fit into any suitable sized vessel. For example, the LPA, RPA, and PT do not have the same or uniform intravascular diameter as one another, and the anchor 2200 is configured to expand to contact the vessel wall at all suitable locations of the LPA, RPA, and PT. In implementations such as ablation around the renal arteries, the anchor 2200 is configured to expand to contact the vessel wall at all suitable locations within the left and right renal arteries.

[0232] The struts 2204 may be self-expanding. For example, the anchor 2200 may be collapsed and deployed by retracting and advancing the outer sheath 2210 to expose or cover the struts 2204. The outer sheath 2210 is retracted proximally in the direction of arrow 2208 to allow the struts 2204 to at least partially self-expand. The anchor 2200 is returned to a collapsed state by advancing the outer sheath 2210 distally in the direction of arrow 2209 to apply a radially inward force to the struts 2204, collapsing them. In some embodiments, the outer sheath 2210 may be advanced distally, deploying the struts 2204, and retracted proximally to collapse the struts (e.g., using a push-pull mechanism, such as a pull wire, extending through the distal portion 502).

[0233] In some embodiments, the outer sheath 2210 may be used in conjunction with an umbrella type extension. For example, the outer sheath 2210 may protect the vasculature from the struts 2204 during navigation to the target location, and vice versa. For another example, the outer sheath 2210 may have a lubricious surface to aid in navigation. For another example, the outer sheath 2210 may carry one or more sensors useful for measuring parameters in the vicinity of the transducer assembly 2201. For another example, the outer sheath may include a Swan-Ganz balloon to float the catheter to the target location (without the use of a separate Swan-Ganz catheter).

[0234] The outer diameter of the distal portion of the catheter, including the transducer assembly 2201, anchor 2200, and optionally the outer sheath 2210, is about 3 mm to about 12 mm (e.g., about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 10 mm, about 12 mm, and ranges between such values). A smaller diameter distal portion can allow for insertion through a smaller incision. A smaller incision can reduce scar size, potential infection site size, and / or healing time.

[0235] In some embodiments, a combination of partial self-expansion and umbrella type expansion is used. For example, the outer sheath 2210 may be retracted proximally, which can allow the struts 2204 to be partially self-expanding. This partial self-expansion may be sufficient to seal against the vessel wall. In some alternative implementations in which anchoring is not desired, but spacing between the transducer assembly 2201 and the vessel wall may be provided by the struts being partially self-expanded, this partial self-expansion may be sufficient. If partial self-expansion is not sufficient (e.g., to seal against the vessel wall sufficiently), umbrella type expansion may be used to further expand the struts 2204, for example, as described herein.

[0236] The plurality of struts 2204 preferably comprise a shape memory material (e.g., Nitinol, Chrome Cobalt, MP35N, 35NPT, Elgiloy, etc.). Even in embodiments where the anchor 2200 is not completely self-expanding, the shape memory material may help the plurality of struts 2204 to maintain their shape, respond to external forces (including device-based expansion forces), etc. Other strut materials are also possible (e.g., stainless steel).

[0237] In some embodiments, the struts 2204 are not aligned with the transducer. For example, even if the transducer comprises four wedge-shaped pieces and the anchor 2200 comprises four struts 2204, the struts 2204 do not necessarily have to be aligned with the transducer pieces (e.g., at their intersections). Rather, the struts 2204 can be independent of the transducer pieces.

[0238] The transducer assembly 2201 may be substantially radially centered between the struts 2204. If the struts expand uniformly, the transducer assembly 2201 may be substantially centered within the vessel. Centering the transducer assembly 2201 within the vessel may help ensure that tissue all around the vessel is treated. For example, if the transducer assembly 2201 has a penetration radius of 20 mm and is centered within a vessel where the vessel diameter is 18 mm, the penetration depth all around the vessel is approximately 11 mm. If the same transducer assembly 2201 were not centered within the same vessel, the penetration depth may be 3 mm in one direction and 19 mm in the opposite direction, either or both of which may affect undesired tissue. It should be understood that these numbers are for illustrative purposes and the real numbers would take into account, for example, ultrasound absorption, diffraction at interfaces, Snell-Descartes law, etc.

[0239] 22A and 22B diagrammatically illustrate the locations of several exemplary radiopaque markers 2270, 2272, 2274, 2276. Marker 2270 is at the distal tip of the distal portion. Marker 2270 may be spaced slightly away from the distal tip of the distal portion. Marker 2272 is at the distal end of the outer sheath 2210. Marker 2272 may be spaced slightly away from the distal end of the outer sheath 2210. Marker 2274 is at the distal end of the anchor 2200. Marker 2274 may be spaced slightly away from the distal end of the anchor 2200. Marker 2276 is at the proximal end of the anchor 2200. Marker 2276 may be spaced slightly away from the proximal end of the anchor 2200. In some embodiments, the material of anchor 2200 may be radiopaque such that marker 2274 and / or marker 2276 are the visible ends of anchor 2200 (e.g., no separate marker material is used).

[0240] Marker 2270 can be used to control the distal tip of the device, for example, to inhibit or prevent distal perforation of the treatment site and / or inhibit or prevent application of pressure on small vessels. Marker 2272 can be used, for example, to determine the position of outer sheath 2210 relative to other components. If marker 2272 is distal to marker 2274, the user knows that anchor 2200 is covered by outer sheath 2210. If marker 2272 is proximal to marker 2276, the user knows that anchor 2200 is not covered by outer sheath 2210. The user may observe the relative positions of markers 2274, 2276 to gauge the expansion of anchor 2200. For example, as can be seen in Figures 22A and 22B, when the markers 2274, 2276 are further apart, the anchor 2200 is closer to the collapsed position, and when the markers 2274, 2276 are closer together, the anchor 2200 is closer to the deployed or expanded position. In some embodiments, the distance between the markers 2274, 2276 may be measured (e.g., using fluoroscopy measurements directly (e.g., using the length of the transducer 2201 for scale), using markings on the device, etc.) to determine the range of expansion, which may include the diameter of the vessel at the deployment site. The range of expansion and / or the diameter of the vessel at the deployment site may be used to set neuromodulation (e.g., ablation) parameters. The radiopaque markers described herein may be implemented in other catheter systems described herein, e.g., catheter system 100.

[0241] The transducer assembly 2201 may be longitudinally movable relative to the distal shaft 2202 and / or the proximal shaft 2212 (e.g., by being coupled to an independent transducer shaft). For example, although the transducer assembly 2201 is illustrated as being large relative to the anchor 2200, the transducer assembly 2201 may extend over a much smaller longitudinal extent of the anchor 2200. The transducer assembly 2201 may move relative to the anchor 2200 to perform multiple ablations without collapsing and redeploying the anchor. For example, the transducer assembly 2201 may be at a first distal position within the anchor 2200 to perform a first ablation, then retracted proximally to a second intermediate position within the anchor 2200 without moving the anchor 2200 to perform a second ablation, and then retracted further proximally to a third proximal position within the anchor 2200 without moving the anchor 2200 to perform a third ablation. In some embodiments, the transducer assembly 2201 may be at a first proximal position within the anchor 2200 to perform a first ablation, then advanced distally to a second intermediate position within the anchor 2200 without moving the anchor 2200 to perform a second ablation, and then advanced further distally to a third distal position within the anchor 2200 without moving the anchor 2200 to perform a third ablation. In some embodiments, the transducer assembly 2201 may be at a first intermediate position within the anchor 2200 to perform a first ablation, then advanced distally to a second distal position within the anchor 2200 to perform a second ablation without moving the anchor 2200, and then retracted proximally to a third proximal position within the anchor 2200 to perform a third ablation without moving the anchor 2200. The mobility of the transducer assembly 2201 within the anchor 2200 is generally more important than the precise implementation of the movement.While this may be mechanically more complex (e.g., in contrast to the transducer assembly 2201 being mounted between the distal shaft 2202 and the proximal shaft 2212), such movement may reduce operation time by reducing or eliminating anchor collapse, repositioning, and redeployment after each of the first and second ablations.

[0242] The struts 2204 may have a thickness of about 30 μm to about 500 μm (e.g., about 30 μm, about 40 μm, about 50 μm, about 60 μm, about 70 μm, about 80 μm, about 90 μm, about 100 μm, about 110 μm, about 120 μm, about 130 μm, about 140 μm, about 150 μm, about 500 μm, and any range between these values). This thickness is measured in the radial direction of each individual strut 2204. The thinner the struts 2204, the less likely they are to cause interference or scattering in the ultrasound signal. For example, the struts 2204 may cast an ultrasound shadow, resulting in an area covered by the shadow that is not ablated.

[0243] The plurality of struts 2204 may comprise between about 4 struts and about 64 struts (e.g., about 4 struts, about 6 struts, about 8 struts, about 10 struts, about 12 struts, about 16 struts, about 20 struts, about 30 struts, about 40 struts, about 50 struts, about 64 struts, and ranges between such values).

[0244] Applicants have discovered that strut thicknesses of less than about 100 μm do not significantly affect the ultrasound signal. In embodiments having thin struts (e.g., about 30 μm to about 100 μm), a larger number of struts (e.g., about 100 μm) may be used to increase the amount of total adhesion force onto the vessel wall and provide suitable anchoring.

[0245] Some embodiments may include thicker struts (e.g., about 110 μm to about 500 μm). For example, interference or shadowing caused by thicker struts can be advantageously used to protect portions of the vessel wall while ablating targeted tissue (e.g., including nerves) beyond the vessel wall. Thicker struts may provide higher radial forces on the vessel wall for more secure anchoring.

[0246] A balance between reducing interference or shadowing produced by the struts 2204 and sufficient radial force may be desirable. The number or quantity of struts 2204 may be varied to counter any interference or shadowing and / or to increase radial force, as may be appropriate. Fewer struts 2204 may reduce potential interference and shadowing. A greater number of struts 2204 may increase radial force.

[0247] FIG. 22C illustrates another embodiment of the anchor 2220. FIG. 22C illustrates the anchor 2220 in a collapsed or delivered state. FIG. 22D illustrates the anchor 2220 in a deployed state. The anchor 2220 comprises a plurality of struts 2224 that are twisted around the transducer 2221. The plurality of struts 2224 may be collapsed and deployed via any of the methods described herein (e.g., self-expanding, umbrella-type, and combinations thereof). The twisted configuration of the plurality of struts 2224 can reduce the overall interference or ultrasound shadow that the plurality of struts 2224 may create across the transducer assembly 2221. For example, there is little interference produced in the longitudinal direction by each strut 2224 because the twisted configuration will only cover a portion of the transducer assembly 2221 in the longitudinal direction instead of the entire section of the transducer assembly 2221 in the longitudinal direction.

[0248] As shown in FIG. 22D, there may be portions of one or several struts 2224 along any longitudinal line, but no longitudinal line is entirely a strut. The twisted configuration allows coverage by struts 2224 to be positioned within various sections of the transducer assembly 2221 such that the entire longitudinal section is not covered. Combined with the application of power to the length of the transducer assembly 2221 and the focusing provided by the lens, the twisted configuration of multiple struts 2224 may increase the probability that all targeted tissue (e.g., including nerves) is ablated due to the reduction in potential interference or shadowing caused by the struts 2224. The twisted struts 2224 may provide a partial lateral dimension to the anchor 2220, which may help provide better vessel wall adhesion, e.g., provide a counter force against longitudinal blood flow. Straight struts 2204 may be less likely to cause blood turbulence. The various strut configurations described herein may be implemented within the other catheter systems described herein, for example, catheter system 100.

[0249] 23A and 23B illustrate an example transducer assembly including a transducer 2240 configured to slide across the inner shaft 2212 as the anchor is deployed. As the anchor 2260 is deployed, the transducer 2240 is translated across the inner shaft 2212 to ablate several ablation sites (e.g., first ablation site 2242a and second ablation site 2242b) at one anchoring location. The transducer 2240 may be translated to one, two, three, four, five, or more ablation sites or as many as desired at one anchoring location. This method of translating the transducer 2240 can reduce treatment time by reducing the amount of time the anchor 2260 is collapsed and moved and then redeployed within the vessel. In some embodiments, the anchor 2260 may be only partially collapsed or uncollapsed prior to movement (e.g., it may be worth incurring possible vessel wall damage in order to reduce procedure time by moving an at least partially expanded anchor). The transducer 2240 may be connected to a pull and / or push wire 2244 to move the transducer 2240 along the inner shaft 2212.

[0250] 23C-23E illustrate an exemplary method of rotating the anchor 2250 between ablations. Rotation of the anchor 2250 may counter or account for any interference caused by a shadow created by the anchor 2250. After a first ablation is performed in the deployed state as shown in FIG. 23C, the anchor 2250 may be collapsed to a delivery state as shown in FIG. 23D. The anchor 2250 may then be rotated as shown by arrow 2254. The anchor 2250 is preferably not moved longitudinally during rotation. The anchor 2250 is then redeployed with the struts touching a different portion of the vessel wall as shown in FIG. 23E. The struts of anchor 2250 are in a different position than in Fig. 23C, which results in any interference or shadowing occurring in a different area of ​​the vessel, which allows transducer 2252 to ablate the tissue that is shadowed in Fig. 23C, thereby providing a more complete ablation. This process will be repeated as many times as desired to account for interference or shadowing.

[0251] 24A diagrammatically illustrates an exemplary embodiment of a catheter 2400 comprising a handle 2404 and an elongated shaft 2402. A distal portion of the elongated shaft 2402 may comprise a transducer assembly, an anchor, etc. The handle comprises an actuator 2406. The actuator 2406 may be used to collapse and / or deploy the anchor 2400. The actuator 2406 may comprise, for example, a thumb wheel or a slider. In some embodiments, the actuator 2406 comprises a slider, and the actuator 2406 can slide along a path 2410 in either direction, as indicated by arrow 2408. In some embodiments, the actuator 2406 can inform the operator of the inner diameter of the vessel. For example, as described herein, the longitudinal distance between the distal shaft 2402 and the proximal shaft 2412 is related to the radial expansion of the struts 2404. When the actuator 2406 retracts the distal shaft 2402 proximally a certain distance, the corresponding extent of radial expansion of the struts 2404, and therefore the diameter of the vessel at which the struts 2404 stopped expanding, can be determined. The handle 2404 may include markings along the path 2410. The vessel diameter information may be used to select energy values ​​(e.g., time and / or modulation) to increase the safety and effectiveness of the treatment.

[0252] In some embodiments, the handle 2404 may include a button 2412 configured to initiate ablation. A foot switch, a software button located on the instrument touch screen, a mouse click, and / or other ablation-inducing input are also possible.

[0253] In embodiments that include an outer sheath, the handle 2404 may include a mechanism for retracting the outer sheath proximally and / or advancing it distally (e.g., a second actuator). In some embodiments, the outer sheath may be directly manipulated by the user (e.g., distal to the handle 2404 and / or proximal to the handle 2404).

[0254] In some embodiments, the handle 2404 may comprise components for retracting the distal portion of the elongate shaft a controlled distance between ablation sites, as described in further detail herein. For example, the handle 2404 may comprise a third actuator. If the handle 2404 comprises multiple actuators, the actuators may be labeled with indicia (e.g., letters or numbers), comprise different colors, etc. Preferably, the actuators are each at least partially different. For example, multiple actuators, each configured to slide within a path, may have different shapes, surface textures, colors, etc. In some embodiments, the actuators are distinguishable by being different types of actuators (e.g., thumb wheels for movement of the outer sheath, sliders for deployment of anchors, knobs for controlled retraction of the distal portion, etc.).

[0255] 24B diagrammatically illustrates another exemplary embodiment of a catheter 2420 comprising a handle 2424 and an elongated shaft 2402. The handle 2424 may comprise features of the handle 2404. The handle 2424 comprises a proximal portion 2426 and a distal portion 2428. The proximal portion 2426 may be rotated relative to the distal portion 2428, as indicated by arrow 2422, to advance or retract the distal portion of the catheter 2420 within the vessel. Rotation of the proximal portion 2426 is translated into linear motion, for example, using a helix, worm gear, rack and pinion, or the like, to advance or retract the distal portion of the catheter 2420 within the vessel. Rotating the proximal portion 2426 in one direction advances the distal portion of the catheter 2420, and rotating the proximal portion 2426 in the opposite direction retracts the distal portion of the catheter 2420. The handle 2424 may include detents to help the user determine the appropriate amount of rotation and thus movement of the distal portion of the catheter 2420. For example, each controlled turn of the proximal portion 2426 may retract the distal portion of the catheter proximally a set distance, for example, about 0.25 cm to about 2 cm (e.g., about 0.25 cm, about 0.5 cm, about 1 cm, about 1.5 cm, about 2 cm, and ranges between such values). Distal advancement of the distal portion is also possible.

[0256] In some embodiments, the distal portion of the catheter 2420 is advanced to a first target location, such as a distal location in the LPA. The anchor is deployed and tissue surrounding the first target location is ablated. The anchor is then collapsed and the proximal portion 2424 is rotated, retracting the distal portion of the catheter 2420 proximally, for example, by 0.5 cm, to a second target location. The handle 2424 may include an interlock that inhibits or prevents rotation of the proximal portion 2426 when the anchor is in the deployed state. The anchor is redeployed and tissue surrounding the second target location is ablated. This collapse, retract (or otherwise moved), redeploy, ablate sequence can be repeated over the length of the LPA and then the length of the PT. The distal portion of the catheter 2420 is then advanced to an Nth target location, such as a distal location in the RPA (e.g., after user manipulation of the guidewire). The anchor is redeployed and tissue surrounding the Nth target location is ablated. The collapse, retract (or otherwise move, such as distal advance), redeploy, ablate sequence can be repeated over the length of the RPA. The handle configurations described herein may be implemented within other catheter systems described herein, for example, catheter system 100.

[0257] Any sequence of treatment of the pulmonary artery is possible, for example: LPA, then PT, then RPA; RPA, then PT, then LPA; LPA, then RPA, then PT; RPA, then LPA, then PT; PT, then RPA, then LPA; PT, then LPA, then RPA. Preferably, the PT is ablated after the LPA or RPA to reduce navigation. In some embodiments, the PT may be ablated after the LPA and after the RPA.

[0258] 25A and 25B illustrate another exemplary embodiment of an anchor 2500. FIG. 25A illustrates the anchor 2500 in a collapsed state. In some embodiments, an outer sheath 2510 inhibits or prevents the anchor 2500 from expanding while in the collapsed state. FIG. 25B illustrates the anchor 2500 in a deployed state. The anchor 2500 comprises components on each side of a transducer assembly 2501. The anchor 2500 comprises two braid configurations 2502. Additional braid configurations 2502 are also possible. A first braid configuration 2502 is distal to the transducer assembly 2501 and a second braid configuration 2502 is proximal to the transducer assembly 2501. For example, a braid configuration 2502 with a high braid angle can provide superior radial force compared to multiple struts with similar thickness, etc.

[0259] 26A and 26B illustrate another embodiment of the anchor 2600. FIG. 26A illustrates the anchor 2600 in a collapsed state. In some embodiments, an outer sheath inhibits or prevents the anchor 2600 from expanding while in the collapsed state. FIG. 26B illustrates the anchor 2600 in a deployed state. The anchor 2600 comprises a plurality of struts 2602 on each side of the transducer assembly 2601. The anchor 2600 comprises two plurality of struts 2602. Additional plurality of struts 2602 are also possible. The plurality of struts 2602 may be configured and operate in any of the manners as the plurality of struts 2204 described herein. For example, the size and shape of the struts 2602 may be any of the embodiments described herein, and the deployment and collapse of the anchor 2600 may occur in any of the manners described herein. The multiple struts 2602 can provide simpler and / or more reproducible manufacturing as compared to the braided configuration 2502, for example, in terms of attachment to the proximal and / or distal shafts.

[0260] In some embodiments, the anchors 2500, 2600 are deployed by pushing the braided configuration 2502 or the plurality of struts 2602 together, causing the braided configuration 2502 or the plurality of struts 2602 to recurve radially outward, as shown in FIGS. 25B and 26B. In some embodiments, the anchors 2500, 2600 are self-expanding. The anchors 2500, 2600 may be collapsed and deployed by moving the outer sheath 2510 (FIGS. 25A and 25B) to cover or expose the anchors 2500, 2600. The outer sheath 2510 is moved in the direction of arrow 2506 to deploy the anchors 2500, 2600. Additionally or alternatively, the anchors 2500, 2600 may be collapsed and deployed via a pull wire connected to one, some, or all of the braided configuration 2502 or the plurality of struts 2602. The anchors 2500, 2600 deploy when the pull wire is pulled, and the anchors 2500, 2600 collapse when the pull wire is advanced. In addition to or as an alternative to the pull wire, a shaft or tube may be used to push and / or pull the proximal and / or distal portions of the anchor to deploy and / or collapse the anchor. In some embodiments, the pull wire may be biased toward a collapsed state for a fail-to-act collapse configuration. In some embodiments, the fail-to-act collapse configuration may be achieved by thermoforming the anchor in a collapsed configuration. In one such embodiment, a pushing mechanism may be used to achieve the deployed configuration. The anchor may be actuated and / or left actuated by a wheel locker in the handle. Fail-to-act collapse can collapse the anchor upon a failure (e.g., of the wire, shaft, etc.) while deployed in a subject.

[0261] 27A-27D illustrate another embodiment of the anchor 2700. FIG. 27A illustrates the anchor 2700 in a collapsed state. In the embodiment illustrated in FIG. 27A, the outer sheath 2710 inhibits or prevents the anchor 2700 from expanding radially, e.g., causing stress-induced martensite. FIG. 27B illustrates the anchor 2700 in an deployed state. When the petal configurations 2702 are not confined by the outer sheath 2710, the anchor 2700 can self-expand due to a phase change to austenite. The anchor 2700 comprises a petal configuration 2702 on each side of the transducer assembly 2701. The anchor 2700 comprises two petal configurations 2702. Additional petal configurations 2702 are also possible.

[0262] The petal configuration 2702 comprises one or more wires shaped as a flower with multiple petals 2706. The petals 2706 may overlap circumferentially. The wires may be shaped in the deployed state such that the petal configuration 2702 is self-expanding. In some embodiments, the anchor 2700 includes float sections (e.g., sections generally parallel to the longitudinal axis) at the tips of the petals to increase the contact surface between the anchor 2700 and the vessel wall. The increased contact surface may reduce the radial force applied to the vessel wall while still achieving the same anchoring (e.g., providing a substantially constant transducer assembly 2701 position under the same force, such as blood flow).

[0263] The anchor 2700 may be configured in multiple orientations. The petal configurations 2702 may be oriented to open facing a distal portion of the catheter, for example, as shown in FIG. 27B. The petal configurations 2702 may be configured to face a handle of the catheter (e.g., as described herein), for example, as shown in FIGS. 27A-27D. The petal configurations 2702 may be configured to face each other. The petal configurations 2702 may be configured to face away from each other.

[0264] The anchor 2700 may be self-expanding. The anchor 2700 may be collapsed and deployed by moving the outer sheath 2710 to cover or expose the petal configuration 2702. In some embodiments, the anchor 2700 is collapsed and deployed via a pull wire. If the petal configuration 2702 faces the handle, the pull wire may be used to collapse the petal configuration 2702 that is not collapsible by the outer sheath 2710 due to the direction in which the petal configuration 2702 faces.

[0265] Figure 27C is a top view of an exemplary petal configuration for the anchor 2700 of Figure 27A. The petals may have a circumferential width 2720 of about 5 mm to about 15 mm (e.g., about 5 mm, about 7 mm, about 9 mm, about 11 mm, about 13 mm, about 15 mm, and ranges between such values). The base of the petal configuration may be configured to create an angle 2722 of about 10 degrees to about 20 degrees (e.g., about 10 degrees, about 12 degrees, about 14 degrees, about 16 degrees, about 18 degrees, about 20 degrees, and ranges between such values).

[0266] FIG. 27D is a side view of the exemplary petal configuration of FIG. 27A. The top portion of the petal may have a radius 2724 of about 1 mm to about 8 mm (e.g., about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, and ranges between such values). The distance 2726 between the base of the petal configuration and the center of the petal diameter may be about 12 mm to about 20 mm (e.g., about 12 mm, about 14 mm, about 16 mm, about 18 mm, about 20 mm, and ranges between such values). The distance 2728 between the base of the petal configuration and the beginning of the petal may be about 2 mm to about 8 mm (e.g., about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, and ranges between such values). The distance 2730 between the angle of the petal and the beginning of the arc of the petal may be from about 0.5 mm to about 2.5 mm (e.g., about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, and ranges between such values).

[0267] The anchors 2500, 2600, 2700 can apply a radial force on the vessel wall and anchor the transducer assemblies 2501, 2601, 2701 within the vessel. The anchors 2500, 2600, 2700 are configured to conform to different diameters of the vessel as described herein. For example, the PT is typically larger than the diameter of the LPA and RPA, and the anchors 2500, 2600, 2700 expand according to the diameter of the ablation site. Depending on the diameter of the vessel, it may not be possible to achieve the delivery state shown in Figures 8B, 9B, and 10B, but the expansion of the anchors 2500, 2600, 2700 such that the anchors 2500, 2600, 2700 are able to maintain a substantially constant position of the transducer assemblies 2501, 2601, 2701 within the vessel may be considered as a deployed state. Ablation preferably occurs when the anchors 2500, 2600, 2700 are not in a deployed or delivered state.

[0268] Anchors 2500, 2600, 2700 are proximal and distal to transducer assemblies 2501, 2601, 2701, respectively. Anchors 2500, 2600, 2700 do not overlap longitudinally with transducer assemblies 2501, 2601, 2701, do not cast a cast shadow, scatter acoustic energy, or otherwise block ablation energy. Anchors 2500, 2600, 2700 can enable single ablation without rotation, since the ablation energy is circumferential and cannot be blocked.

[0269] 25A and 25B illustrate two braided configurations 2502, Figures 26A and 26B illustrate two struts 2602, and Figures 27A-27D illustrate two petal configurations 2702, some embodiments of the anchor may comprise any number of braided configurations, struts, petal configurations, combinations thereof, and / or the like. For example, an anchor may comprise one braided configuration and one strut, one braided configuration and one petal configuration, or one strut and one petal configuration, e.g., providing certain benefits of each type of anchor.

[0270] 28A-28D illustrate another embodiment of an anchor 2800. FIG 28A illustrates the anchor 2800 in a collapsed state. FIG 28B illustrates the anchor 2800 in a deployed state. The anchor 2800 comprises one petal configuration 2802. The petal configuration 2802 may be configured in any of the described embodiments of the petal configuration 2702.

[0271] The anchor 2800 can be configured with a petal configuration 2802 that faces proximally. When the petal configuration 2802 is proximal to the transducer assembly 2801, the petal configuration 2802 faces away from the transducer assembly 2801 (e.g., as shown in FIG. 28B ). When the petal configuration 2802 is distal to the transducer assembly 2801, the petal configuration 2802 faces toward the transducer assembly 2801. The anchor 2800 may be deployed and collapsed via an outer sheath 2810 and / or a pull wire 2804 that is connected to one, some, or all of the petals of the petal configuration 2802. If the pull wire 2804 is not connected to all the petals, the overlap of the petals may cause all the petals to collapse when the pull wire 2804 is pulled. 28C and 28D illustrate the use of an outer sheath 2810 to deploy and collapse the anchor 2800. The outer sheath 2810 is positioned over a distal portion of the catheter. The outer sheath 2810 is advanced distally in the direction of arrow 2808, allowing the anchor 2800 to expand to a deployed state. The outer sheath 2810 is then retracted proximally, collapsing the anchor 2800.

[0272] 29A and 29B illustrate another embodiment of an anchor 2900. FIG. 29A illustrates the anchor 2900 in a collapsed state. In the embodiment illustrated in FIG. 29A, an outer sheath 2910 inhibits or prevents the anchor 2900 from radially expanding. For example, the anchor 2900 may include a ring balloon 2902 coupled to a number of self-expanding struts 2904. The struts 2904 may be coupled to the ring balloon 2902 at equally spaced locations along the circumference of the ring balloon 2902. FIG. 29B illustrates the anchor 2900 in a deployed state. When the ring balloon 2902 and struts 2904 are not confined by the outer sheath 2910, the struts 2904 may self-expand. In addition, the ring balloon 2902 may be inflated, for example, via an inflation lumen extending through one of the struts of the plurality of struts 2904, to fully deploy the anchor 2900 such that the ring balloon 2902 contacts the inner wall of the blood vessel, thereby centering the transducer 2901 within the vessel. Thus, the distance between the tip 2911 and the transducer 2901 may be minimized, and the transducer 2901 may further be visually located without additional movement during anchor deployment. Furthermore, the anchor 2900 coincides with the location of the transducer 2901.

[0273] 30A and 30B illustrate another embodiment of an anchor 3000. FIG. 30A illustrates the anchor 3000 in a collapsed state. The anchor 3000 includes a plurality of individually inflatable balloons 3002, each coupled to an individual strut of a plurality of struts 3004. Each of the struts 3004 may include an inflation lumen for inflating the balloon 3002. Additionally, the anchor 3000 includes a sleeve 3006 that is wrapped circumferentially around the balloon 3002. FIG. 30B illustrates the anchor 3000 in a deployed state. For example, the anchor 3000 may be delivered to a target vessel within a delivery sheath such that upon retraction of the sheath to expose the anchor 3000, the balloon 3002 may be inflated, as shown in FIG. 30B, thereby centering the transducer 3001 within the vessel. In the deployed state, the sleeve 3006 contacts the inner wall of the blood vessel and blood is allowed to flow across the anchor 3000 between the balloon 3002 and the transducer 3001. Furthermore, the transducer 3001 can be visually positioned without additional movement during anchor deployment, with the anchor 3000 coinciding with the location of the transducer 3001.

[0274] 31A and 31B illustrate another embodiment of an anchor 3100. FIG. 31A illustrates the anchor 3100 in a collapsed state. The anchor 3100 includes a coil 3102 that is wrapped circumferentially around a longitudinal axis of the anchor 3100. A distal end of the coil 3102 may be coupled to a tip 3111 disposed at an end of an inner catheter 3104, and a proximal end of the coil 3102 may be coupled to a distal end of an outer catheter 3110, the inner catheter 3104 being slidably movable within the outer catheter 3110. Thus, relative movement between the inner catheter 3104 and the outer catheter 3110 may transition the coil 3102 between a collapsed state, as shown in FIG. 31A, and a deployed state, as shown in FIG. 31B, by moving the proximal and distal ends of the coil 3102 toward and away from one another. In some embodiments, the coil 3102 may be self-expanding, for example, biased toward the deployed state. Additionally, the transducer 3101 may be visually positioned without additional movement during anchor deployment, where the anchor 3100 coincides with the location of the transducer 3101.

[0275] 32A and 32B illustrate another embodiment of an anchor 3200. FIG. 32A illustrates the anchor 3200 in a collapsed state. In the embodiment illustrated in FIG. 32A, the outer sheath 3210 inhibits or prevents the anchor 3200 from radially expanding. For example, the anchor 3200 may include a proximal coil 3202a disposed between the catheter 3204 and the transducer 3201 and a distal coil 3202b disposed between the tip 3211 and the transducer 3201. The proximal coil 3202a and the distal coil 3202b may be formed from a shape memory metal, for example, Nitinol, such that the proximal coil 3202a and the distal coil 3202b are biased toward the expanded state. In response to retraction of the sheath 3210, the proximal coil 3202a and the distal coil 3202b may transition to an expanded state, as shown in FIG. 32B, thereby centering the transducer 3201 within the blood vessel.

[0276] 33A-33D illustrate another embodiment of an anchor 3300. The anchor 3300 comprises a loop wire 3302. The anchor 3300 may comprise one, two, or more loop wires 3302. FIGS. 33C and 33D illustrate the loop wire 3302. FIG. 33A illustrates the anchor 3300 in a collapsed state. An outer sheath as described herein may be used to inhibit or prevent the anchor 3300 from expanding. FIG. 33B illustrates the anchor 3300 in a deployed state.

[0277] The loop wire 3302 may be positioned distal and proximal to the transducer assembly 3303 to anchor the transducer assembly 3303 within the vessel. In embodiments comprising a single loop wire 3302, the loop wire 3302 may be located distal or proximal to the transducer assembly 3303. In some embodiments, the loop wire 3302 is self-expanding and can be actuated by pushing the wire (e.g., one or both legs) from the proximal side of the catheter. The loop wire 3302 is then collapsed by pulling the wire.

[0278] All of the anchor embodiments described herein may be modified and combined to produce additional embodiments. For example, all of the embodiments may consist of one, two, three, or four anchors. In embodiments with more than one anchor, the anchors may be of different types. For example, an anchor embodiment may include multiple struts and a braided configuration. Any combination of the disclosed embodiments may be possible. All methods of deploying and collapsing the different anchor embodiments may be applied to any of the anchor embodiments, including, but not limited to, the umbrella method, moving an outer sheath, using a pull wire, using an actuation shaft (e.g., a telescoping shaft), and using a self-expanding material. In embodiments in which neuromodulation is provided by, for example, acoustic energy (e.g., ultrasound), microwave energy, radio frequency (RF) energy, thermal energy, electrical energy, infrared energy, laser energy, phototherapy, plasma energy, ionization energy, mechanical energy, cryoablation, chemical energy, combinations thereof, and the like, the anchor may optionally push a transducer or other element against the vessel wall.

[0279] As explained above, the distal portion of the catheter system (e.g., the distal region 104 of the catheter system 100) is flexible enough to navigate various vessels and cavities such as the ventricles, and stiff enough to be advanced through valves such as the tricuspid and pulmonary valves. This combination of flexibility and stiffness can cause undesirable effects when the distal portion is tethered ablation. FIG. 34A illustrates an example catheter in a vessel 3401 that is not properly tethered. As shown in FIG. 34A, the transducer assembly 3420 is assumed to be tethered for ablation. The curvature of the catheter proximate to the anchor pushes the transducer assembly 3420 to the right as the radial force of the anchor cannot overcome the force of the catheter.

[0280] FIG. 34B illustrates an exemplary embodiment of a catheter in which the stiffness of the shaft 3400 proximate the distal portion can be virtually eliminated. To reduce the effect of the shaft 3400 stiffness, some embodiments include a suspension 3402. The suspension 3402 may include a coil or other type of flexible shaft portion configured to relieve some of the constraint forces due to the shaft 3400 stiffness and curvature proximate the distal portion. The suspension 3402 is more flexible than the shaft 3400, which can allow the distal portion to virtually ignore the forces of the shaft 3400, which are absorbed by the suspension 3402. The suspension 3402 can provide better anchoring and centering of the transducer assembly 3420. The suspension 3420 may include any suitably flexible material.

[0281] A distal portion of the catheter system (e.g., distal region 104 of catheter system 100) may be navigated through the vessel to multiple ablation sites. The distance between the ablation sites may be controlled (e.g., as described with respect to handle 2424 and / or handle 300') and / or monitored. The movement (e.g., retract, advance) features described herein may be used to monitor the distance between the ablation sites. FIG. 35A illustrates a distal portion of the catheter comprising a shaft 3510 and a transducer assembly 3520. The catheter is configured to enter the patient at a venous access point 3502. Venous access points include, but are not limited to, femoral, jugular, and radial artery access points. Any suitable venous access point may be used.

[0282] The shaft 3510 may include electrodes 3504 located along a proximal portion of the shaft 3510. The electrodes 3504 are configured to sense electrical conduction between each electrode to determine the distance the transducer assembly 3520 has been pulled or pushed from the ablation site. In some embodiments, conduction between the first set of electrodes is high impedance while conduction between the rest of the electrodes is low impedance. The difference between the low high impedance and high impedance may be used to account for the electrical conductivity of blood in contact with the electrodes positioned within the body. For example, the electrodes 3504 outside the venous access point 3502 in FIG. 35A will have high impedance while the electrodes 3504 within the vein will have a lower impedance.

[0283] In some embodiments, the electrodes 3504 are located at fixed points along the shaft 3510. The fixed locations allow software running on the instrument (e.g., as described herein) to detect the number of electrodes 3504 that are moved into or out of the body. Tracking the movement of the electrodes 3504 may be used to determine the approximate distance between the position of the transducer assembly 3520 and different ablation sites. In some embodiments, data about the transducer assembly position, the diameter of the deployed anchor, and / or the ablation parameters can be stored. Reports can be produced. Reports from the treatment of various subjects can be combined with data about the effectiveness of the treatment for those subjects to improve the system (e.g., determine ideal ablation intervals, ablation parameters, etc.). An embodiment with electronics may include an interlock, for example, to block or prevent ablation until the catheter is moved to a different ablation site.

[0284] FIG. 35B illustrates another exemplary embodiment of a movement (e.g., retract, advance) feature. The shaft 3510 includes a mark or indicia 3506. Any number of marks 3506 can be used along the shaft 3510. The marks 3506 can be separated by any distance, for example, every half centimeter. The marks 3506 allow the operator to control and monitor the distance between two ablation sites when pulling or pushing the catheter. For example, the marks 3506 can be compared to a stationary object (e.g., an access point). Some embodiments may include additional and / or alternative methods for controlling the distance between two ablation sites when pulling or pushing the catheter. For example, the actuator (e.g., actuator 2406 and / or pusher 1200) may be configured to push or pull the catheter a defined distance with each actuation. For another example, a magnetic beacon can be used. For another embodiment, wheels, with appropriate gearing, can be used.

[0285] In some embodiments, the movement (e.g., retract, advance) features may comprise radiopaque markers on the distal portion of the catheter that may be observed under fluoroscopy. Such movement features may provide the ability to confirm that movement of the catheter (e.g., by manipulating the handle) translates into expected or desired movement within the vessel. Fluoroscopy may also, or alternatively, be used in combination with any of the movement features described herein.

[0286] 36 is a schematic diagram of an exemplary ablation instrument 3600. The instrument 3600 serves as a user interface and provides power to a catheter 3608, e.g., catheter system 100. The instrument 3600 includes a display screen 3602, an ultrasound beam generator 3604, a power monitor 3605, a control computer 3606, a removable catheter connector 3607 between the control computer 3606 and the catheter 3608, and a foot pedal 3610 that may be used to trigger the ablation. The display screen 3602 may be a touch screen. The instrument 3600 may also include other inputs (e.g., a mouse, keyboard, trackball, etc.).

[0287] The ultrasonic beam generator 3604 includes a power amplifier with a 1.5 MHz to 11 MHz output, allowing 200 watts or more of power in continuous wave or pulsed wave mode. The ultrasonic beam generator 3604 supports a programmatic interface, for example, through an internal USB to serial port interface. The interface allows the control computer 3606 to start or stop ultrasonic emission. The ultrasonic beam generator 3604 has embedded firmware that manages the pulse emission communication with the control computer 3604 and can check internal devices such as temperature sensors, fans, etc. (e.g., as described herein).

[0288] Tissue surrounding the pulmonary artery, which may include nerves, can be ablated by applying ultrasonic energy to a transducer, which is focused by a lens. The energy can be applied for a duration of about 0.5 seconds to about 1 minute (e.g., about 0.5 seconds, about 1 second, about 2 seconds, about 3 seconds, about 4 seconds, about 5 seconds, about 6 seconds, about 7 seconds, about 8 seconds, about 9 seconds, about 10 seconds, about 15 seconds, about 30 seconds, about 45 seconds, about 1 minute, and ranges between such values).

[0289] The energy can be from about 20 watts (W) to about 80 W acoustic (e.g., about 20 W, about 30 W, about 40 W, about 50 W, about 60 W, about 70 W, about 80 W, and ranges between such values). The acoustic wattage is based, at least in part, on the power applied and the efficiency of the system, such as the transducer assembly. For example, if the system is 50% efficient, the application of 40 W electricity will result in 20 W acoustic. If the transducer assembly is about 50% to about 80% efficient, the power applied can be from about 25 W to about 160 W to produce about 20 W to about 80 W acoustic.

[0290] Although described herein with respect to ultrasound, other energy modalities are also provided, for example, unfocused ultrasound, focused ultrasound such as high or low intensity focused ultrasound, microwave energy, radio frequency (RF) energy (e.g., monopolar, bipolar, etc.), thermal energy (e.g., cryoenergy, hot or cold provided by a fluid (e.g., water, saline, liquid chemicals, etc.) or gas (e.g., steam), electrical energy (e.g., non-RF electrical energy), infrared energy, laser energy, phototherapy or photodynamic therapy (e.g., in combination with one or more activating agents), plasma energy, ionizing energy delivery (e.g., x-rays, proton beam, gamma rays, electron beam, alpha light, etc.), ablation or The energy modalities may be mechanical energy delivered by abrasive elements, cryoablation, chemical energy or modulation (e.g., chemical ablation), or a combination thereof. In some embodiments, nerve destruction or blocking is accomplished by chemicals or therapeutic agents (e.g., via drug delivery), either alone or in combination with an energy modality. In some embodiments, pharmaceutical agents are combined with neuromodulation (e.g., ablation) as described herein to reduce the dosage or duration of pharmacological therapy and thus reduce side effects. In various embodiments, different energy modalities may be used in combination (either simultaneously or sequentially).

[0291] The power monitor 3605 measures the power using a directional coupler. The directional coupler comprises two coils with ferrites to measure the power without inducing losses due to the measurement. The power monitor 3605 measures the power being sent to the transducer (forward power) and the power being reflected back (reverse power). The forward or reverse power is measured through an analog-to-digital converter that is read in real time by the control computer through an internal USB interface.

[0292] The efficiency and natural frequency of each catheter, transducer, and / or transducer assembly may be measured prior to use, for example, by the manufacturer, another facility, an independent company, and / or the like.

[0293] During the ablation procedure, the user inputs the efficiency and inherent frequency of the transducer being used. Each system can include an indicator of the efficiency of that particular system so that the ultrasound beam generator can account for losses and deliver the appropriate acoustic energy. The indicator may be a fact sheet, input by the user. The fact sheet may be a sticker on the box, on the instructions for use, on the sterile wrapper, on the insert, and / or the like. The indicator may be a bar code or QR code that can be read by an appropriate device. The indicator may be embedded in a flash memory, such as an EPROM, that can be automatically read by the ultrasound beam generator when the catheter 3608 is coupled to the connector 3607. The memory may be a USB stick, SD card, or other hard media that may be required to be inserted into the control computer 3606 for the system to function. The beam generator can use information from the indicator to ensure that the catheter is not reused for multiple procedures (e.g., not at all, unless the user indicates proper sterilization, etc.). Simpler indicators may reduce costs. More complex indicators may reduce the risk of user error.

[0294] During use, the power monitor 3605 will monitor the reverse power (back-reflected, unused power) and compare it to the expected results from the entered data. If the reverse power loss is calculated as too high or indicates a broken transducer (or any problem with the transducer), the procedure can be stopped. For example, if there is too much reverse power, the energy is not being converted to sound and therefore the system is in some variety of fault condition (e.g., a broken cable linking the generator and transducer, a solder break, too many bubbles reflecting power back to the source, parasitic capacitance, etc.).

[0295] The control computer 3606 is configured to assist the user during the procedure. The control computer 3606 controls the user interface, drives the power generator, and controls the power output. For example, the control computer 3606 may be loaded with data from a planning tool to assist in the ablation. This data may include ablation site locations, vessel diameters, distances between ablation sites, etc. The pre-loaded data may include data previously collected via a patient's CT scan images, MRI, IVUS, or other medical scans, images, tests, etc. By knowing this information prior to the procedure, the user may use the control computer 3606 to define the arterial diameter at the ablation site and set or optimize the acoustic power and pulse duration. After the initial phase of positioning the catheter, the treatment may then be automatically monitored using the electrodes described herein to generate a treatment report.

[0296] The treatment report may include a report of the power delivered at each ablation site. Reporting the delivered power will increase the user's overall efficiency and performance per procedure. The report may also indicate different sizes of toroid ablation based on vessel size. For example, the smaller the vessel, the smaller the toroid ablation site should be. If the reported size varies from the expected size, the user may adapt the power or time of ablation based on vessel size. In some embodiments, the anchor may be configured to measure vessel size to be included in the treatment report.

[0297] Sensors (e.g., sensor 3700) may be used to monitor different values ​​during ablation. Figure 37A illustrates an example catheter 3702 with a sensor 3700 located on a distal portion of the catheter 3702. The sensor 3700 may be positioned distal to the transducer 3704 as shown, proximal to the transducer 3704, or in any other suitable configuration. The sensor 3700 may be configured to monitor temperature and track the safety and efficiency of the ablation procedure.

[0298] FIG. 37B is a graph depicting temperature measurements 3710 and pulsed emissions 3708 during ablation. As shown in FIG. 37B, the temperature measurements 3710 should be consistent during ablation. The pulsed emissions 3708 should also be consistent during ablation. The sensor may be configured to indicate if there is a change in temperature or an unexpected temperature. For example, a temperature that is too high may indicate that some anomaly exists and the procedure should be stopped. The temperature measurement sample between two pulsed emissions 3708 may address the viscous heating effect of the thermocouple measurements while the thermocouple is located inside the ultrasound beam. This viscous heating effect may be an artifact that may raise the temperature value and lead to an erroneous measurement. The sensor 3700 may also be configured to measure other values ​​such as blood pressure, flow rate, heart rate, and / or any measurement that may be related to the procedure or patient safety. Any measurements obtained, such as blood pressure, may be used to synchronize the measurements obtained with the ultrasound emissions.

[0299] In some embodiments, the transducer assembly can be used to measure efficiency by measuring the signal returned during neuromodulation. For example, during pulse emission, some energy is reflected back to the transducer as the ultrasound travels through the interface between the media. When tissue is heated, the properties of the medium change, and the change in the energy reflected back from the interface, including the medium, can be detected using the transducer as a sensor. The reflected energy can change the impedance of the transducer assembly, which can induce a modification of the reflected power returned back to the generator. Reflected power signal analysis can be used to detect the threshold when the pulse starts to be efficient enough to, for example, ablate the tissue. This information can be used to stop the pulse emission when the heating is sufficient for neuromodulation. In some embodiments, a multi-element ultrasound probe having a cylindrical shape can be added to the system, separate from the transducer used for neuromodulation, to perform ultrasound thermometry from inside the lumen and inform on the procedure effectiveness.

[0300] 37C illustrates an exemplary catheter system including a second catheter 3724 embodiment that includes a sensor 3722. The second catheter 3724 is separate from the catheter 3726 that includes the transducer. The sensor 3722 on the second catheter 3724 can increase the flexibility of where measurements can be taken. For example, the second catheter 3724 may be positioned in a different vessel than the first catheter 3726, or in a different location in the same vessel as the first catheter 3726. In some embodiments, the first catheter 3726 may include a lumen to help induce the second catheter 3724 to approach its intended location (e.g., have an exit port proximal to the lanceur).

[0301] 37D illustrates a sensor 3730 coupled to the interior of the lens 3732. The sensor 3730 is configured to measure the lens temperature. The sensor 3730 may be a thermocouple sensor. This temperature may be monitored to inhibit or prevent overheating of the transducer 3734 and protect the transducer 3734 from being damaged. The temperature of the lens 3732 may be monitored because a lens with a very high temperature may cause blood clots to form in the patient.

[0302] 37E illustrates multiple sensors 3740 located on the anchor 3742. The sensors 3740 may be thermocouple sensors. One sensor 3740 may be used. In some embodiments, one, some, or all of the struts or other components (e.g., petals) include a sensor 3740. In some embodiments, several struts include a sensor 3740. The sensor 3740 may be used to measure the temperature next to the vessel wall.

[0303] Ablation using any embodiment of the device described herein may occur at multiple ablation sites using the collapse and deploy method. FIG. 38A illustrates the positioning of a first catheter 3804 into a vein 3808 at an insertion site or venous access point 3806. The first catheter 3804 may include a balloon 3802. The first catheter 3804 may be positioned within the vein 3808 and the balloon 3802 may then be inflated. The inflated balloon 3802 may then be carried by blood in the venous vasculature through the right heart and into the first pulmonary artery. A guidewire 3812 may then be navigated to the first pulmonary artery as described above with respect to step 704 of method 700, and the first catheter 3804 may be removed. FIG. 38B illustrates a treatment catheter 3804 positioned over the guidewire 3812. The treatment catheter 3804 is tracked over the guidewire 3812 into the first pulmonary artery as described above with respect to step 710 of method 700. The treatment catheter 3804 may be any of the embodiments described above.

[0304] FIG. 38C illustrates a distal portion of the shaft of a treatment catheter 3804 positioned within a right pulmonary artery (RPA) 3820. An anchor 3822 is positioned and deployed within the RPA 3820 at a first ablation site according to any of the methods described herein, e.g., step 712 of method 700. The anchor 3822 anchors a transducer 3826 within the RPA 3820. The anchor 3822 deploys, contacts the arterial wall 3824, and applies a radial force. After deploying the anchor 3822, tissue (e.g., including nerves) surrounding the first ablation site is ablated as described above with respect to step 714 of method 700. Blocking the nerves around the RPA 3820 can reduce pulmonary hypertension. In some embodiments, neuromodulation is performed (e.g., via ablation, denervation, which may or may not be reversible, stimulation, etc.). Ablation may occur in one location while in the deployed state, or the transducer 3826 may be translated while in a single deployed anchor position to perform multiple ablations, as described herein.

[0305] The ablation site may be ablated for about 0.5 seconds to about 1 minute (e.g., about 0.5 seconds, about 1 second, about 5 seconds, about 30 seconds, about 1 minute, and ranges between such values). During ablation, the frequency used may be about 1.5 MHz to about 11 MHz (e.g., about 1.5 MHz, about 2 MHz, about 2.5 MHz, about 3.5 MHz, about 4.5 MHz, about 6 MHz, about 7.5 MHz, about 9 MHz, about 11 MHz, and ranges between such values). During ablation, the acoustic power used may be about 20 W to about 80 W (e.g., about 20 W, about 30 W, about 40 W, about 50 W, about 60 W, about 70 W, about 80 W, and ranges between such values). This translates to a power range of about 25 W to about 160 W, and ranges between such values.

[0306] Each ablation site may be of different diameter. As shown in Figs. 38C-38I, not all of the diameters of the pulmonary arteries are the same. The anchors 3822 may be deployable to accommodate different diameters as described herein. The locations being ablated may be at different depths or focal points within the vessel wall. The ablation power and time or frequency of the ultrasound beam may be varied to accommodate the varying diameters and depths of the locations to be ablated. In some embodiments, a single set of ablation parameters (e.g., power, duration, frequency) may be used to accommodate various artery diameters. For example, the parameters (e.g., power, duration, frequency) may be set to a target range of lesion depth and may be set to exclude tissue where ablation should not occur. In some embodiments, each ablation may include 50W for 1 minute, followed by 100W for at least 30 seconds, with optional additional pulses at 100W for specific locations.

[0307] After the first ablation site is ablated, the anchor 3822 is collapsed by any of the methods described herein, for example, step 716 of method 700. The distal portion may then be retracted (or advanced) a distance within the RPA 3820, as shown by arrow 3810 in FIG. 38C, and positioned and deployed at the second ablation site, as shown in FIG. 38D. The deploying, ablation, collapsing, and retracting steps may be repeated until a desired amount of tissue around the RPA 3820 (e.g., the entire length of the RPA, 3 / 4, 2 / 3, 1 / 2, 1 / 3, 1 / 4, and ranges between such values) is covered by ablation. Because nerves may act like wires, where a cut at any point along the length may be sufficient to disable the nerve, shorter lengths or segments of the RPA may be ablated to have beneficial effects. Longer lengths may be used to beneficial effect since nerves are not necessarily straight and may branch, start or stop along the length of the RPA, etc. Ablation may be repeated at some or all ablation sites, as discussed herein, to account for any interference or shadowing caused by the anchors.

[0308] FIG. 38E illustrates a distal portion of the shaft of the treatment catheter 3804 positioned within the left pulmonary artery (LPA) 3830. An anchor 3822 is positioned and deployed within the LPA 3830 at a first ablation site according to any of the methods described above. The anchor 3822 anchors the transducer 3826 within the LPA 3830. The anchor 3822 deploys, contacts the arterial wall 3832, and applies a radial force. After deploying the anchor 3822, tissue (e.g., including nerves) surrounding the first ablation site is ablated. Blocking the nerves around the LPA 3822 can reduce pulmonary hypertension. Ablation may occur at one location while in the deployed state, or the transducer 3826 may be translated as described herein to perform multiple ablations while in a single deployed anchor position.

[0309] Once the first ablation site has been ablated, the anchor 3822 may be collapsed by any of the methods described herein. The distal portion may then be retracted (or advanced) a distance within the LPA 3830 as shown by arrow 3812 in FIG. 38E, and positioned and deployed at the second ablation site as shown in FIG. 38F. The deploying, ablation, collapsing, and retracting steps may be repeated until a desired amount of tissue around the LPA 3830 (e.g., the entire length of the LPA, ¾, ⅔, ½, ⅓, ¼, and ranges between such values) has been covered by ablation. Since nerves may act like wires, where a cut at any point along the length may be sufficient to disable the nerve, shorter lengths or segments of the LPA may be ablated to have beneficial effects. Since nerves are not necessarily straight and may branch, start or stop along the length of the LPA, etc., longer lengths may be used to have beneficial effects. Ablation may be repeated at some or all ablation sites, as discussed herein, to account for any interference or shadowing caused by the anchors.

[0310] FIG. 38G illustrates the transducer 3826 positioned within the pulmonary trunk 3840 at a first ablation site. The anchor 3822 may be deployed by any of the methods described above to anchor the transducer 3826 within the pulmonary trunk 3840. The anchor 3822 may be deployed to contact the pulmonary trunk wall 3842 and apply a radial force to center the transducer 3826. The first ablation site may be ablated. Blocking the nerves around the pulmonary trunk 3840 may reduce pulmonary hypertension. The anchor 3822 may be collapsed by any of the methods described herein. The transducer 3826 may then be retracted (or advanced) a distance within the pulmonary trunk 3820 as indicated by arrow 3814 in FIG. 38H and positioned and deployed at a second ablation site as shown in FIG. 38I. The second ablation site may be ablated. The deployment, ablation, collapse, and retraction steps may be repeated until a desired amount of tissue around the pulmonary trunk 3840 (e.g., the entire pulmonary trunk, 3 / 4, 2 / 3, 1 / 2, 1 / 3, 1 / 4, and ranges between such values) is covered by ablation. A shorter length or segment of the PT may be ablated to have beneficial effects, since the nerve may act like a wire, where a cut at any point along the length may be sufficient to disable the nerve. A longer length may be used to have beneficial effects, since the nerve is not necessarily straight, but may branch, start or stop along the length of the PT, etc. Ablation may occur at one location while in the deployed state, or the transducer 3826 may be translated as described herein to perform multiple ablations while in a single deployed anchor position. Ablation may be repeated at some or all ablation sites, as discussed herein, to account for any interference or shadowing caused by the anchor. The treatment catheter may then be removed from the patient.

[0311] This method of ablation may be performed in any order. For example, as described above, the right pulmonary artery (RPA) may be ablated first, followed by the left pulmonary artery (LPA), followed by the pulmonary trunk. Alternatively, the LPA may be ablated first, followed by the RPA, followed by the pulmonary trunk. Any possible order may be used. If required, but not necessarily, ablation sites may be repeated in each vessel. For example, the pulmonary trunk may be ablated twice, and / or one or both of the pulmonary arteries may be ablated twice.

[0312] The devices used during the ablation method may include any of the embodiments described herein. Any of the collapse and deployment methods described herein may be utilized. The movement features described herein may also be utilized in monitoring the location of the distal portion of the catheter 3804 as it is retracted or otherwise moved within the vessel.

[0313] While various illustrative embodiments of the present invention are described above, it will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the invention. The appended claims are intended to cover all such changes and modifications that fall within the true scope of the invention.

Claims

1. 1. A system for reducing neural activity in a nerve surrounding a blood vessel of a patient, the system comprising: A handle and an inner catheter comprising a guidewire lumen extending through at least a portion of the length of the inner catheter; a proximal region of the inner catheter operably coupled to the handle; a transducer assembly comprising a transducer shaft having an ultrasound transducer coupled thereto, the ultrasound transducer configured to be activated to emit ultrasound energy within the blood vessel to reduce neural activity of nerves surrounding the blood vessel, the transducer shaft comprising a lumen sized and shaped to slidably receive the inner catheter therein and a proximal region operably coupled to the handle; an outer catheter comprising a lumen sized and shaped to receive the transducer shaft therein and a proximal region operably coupled to the handle; an expandable anchor comprising a distal end coupled to the inner catheter and a proximal end coupled to the outer catheter such that relative movement between the inner catheter and the outer catheter transitions the expandable anchor between a collapsed delivery state and an expanded deployed state, the expandable anchor being configured in the expanded deployed state to center the ultrasound transducer within the blood vessel of the patient; a sheath comprising a lumen sized and shaped to slidably receive therein the outer catheter and the expandable anchor in the collapsed delivery state, a distal region of the sheath having sufficient stiffness to facilitate transition of the expandable anchor from the expanded deployed state to the collapsed delivery state in response to movement of the distal region of the sheath relative to the expandable anchor without buckling the distal region of the sheath, and a proximal region of the sheath operably coupled to the handle; A system comprising:

2. 2. The system of claim 1, wherein the blood vessel is a pulmonary artery and the ultrasound transducer is configured to be operated to emit ultrasound energy within the pulmonary artery to reduce neural activity of nerves surrounding the pulmonary artery and treat pulmonary hypertension.

3. The system of claim 1 , further comprising a separation sleeve having a lumen sized and shaped to slidably receive the sheath therein, a proximal region of the separation sleeve fixedly coupled to the handle.

4. 4. The system of claim 3, further comprising an introducer having a lumen sized and shaped to slidably receive the sheath and separation sleeve therein, the introducer configured to be fixed relative to the patient and actuated to prevent relative movement between the separation sleeve and the introducer, such that the sheath is movable relative to the separation sleeve without relative movement between the transducer assembly and the patient.

5. 5. The system of claim 4, wherein the introducer includes a valve disposed within the lumen of the introducer such that the introducer is configured to be actuated to prevent relative movement between the separation sleeve and the introducer by actuating the valve relative to the separation sleeve when the separation sleeve is disposed within the lumen of the introducer.

6. The system of claim 1 , wherein the distal end of the inner catheter comprises an atraumatic tip.

7. 7. The system of claim 6, wherein the atraumatic tip comprises a tapered profile such that a cross-sectional area of ​​the atraumatic tip decreases from a proximal end of the atraumatic tip to a distal end of the atraumatic tip.

8. The system of claim 6 , wherein in a delivery configuration, the distal end of the sheath abuts the atraumatic tip.

9. 2. The system of claim 1, wherein the distal end of the expandable anchor is coupled to the inner catheter via a ring slidably disposed on the inner catheter, such that the distal end of the expandable anchor is slidably coupled to the inner catheter.

10. 10. The system of claim 1, wherein the outer catheter is fixedly coupled to the handle and the inner catheter is configured to move relative to the outer catheter and be actuated to transition the expandable anchor between the collapsed delivery state and the expanded deployed state.

11. 2. The system of claim 1, wherein the inner catheter is fixedly coupled to the handle and the outer catheter is configured to move relative to the inner catheter and be actuated to transition the expandable anchor between the collapsed delivery state and the expanded deployed state.

12. The system of claim 1 , wherein the expandable anchor comprises a plurality of posts.

13. The system of claim 12 , wherein the plurality of struts comprises a plurality of diamond shaped struts.

14. The system of claim 1 , wherein the expandable anchor comprises a shape memory material.

15. 10. The system of claim 1, wherein the expandable anchor, in the expanded deployed state, comprises a radial force that exceeds a stiffness force of the inner catheter, the transducer shaft, the outer catheter, and the distal region of the sheath.

16. The system of claim 1 , wherein a stiffness of the distal region of the sheath exceeds a stiffness of the proximal region of the sheath.

17. The system of claim 16 , wherein an outer diameter of the distal region of the sheath is greater than an outer diameter of the proximal region of the sheath.

18. 2. The system of claim 1, wherein the transducer shaft and the outer catheter are sealed to create a fluidically sealed cavity therebetween, and at least one cable is disposed within the fluidically sealed cavity to provide electrical energy to the ultrasound transducer for emitting the ultrasonic energy.

19. 10. The system of claim 1, further comprising a generator operably coupled to the ultrasonic transducer, the generator configured to be actuated to provide electrical energy to the ultrasonic transducer and cause the ultrasonic transducer to emit ultrasonic energy.

20. a sensor configured to measure a temperature of the ultrasonic transducer; 20. The system of claim 19, wherein the generator comprises a control loop configured to adapt the electrical energy provided to the ultrasonic transducer if a temperature of the ultrasonic transducer exceeds a predetermined threshold.

21. the transducer is configured to convert acoustic energy reflected from an adjacent anatomical airway structure into electrical energy; 20. The system of claim 19, wherein the generator comprises a control loop configured to stop emitting ultrasonic energy if the electrical energy exceeds a predetermined threshold, the electrical energy indicative of a level of acoustic energy reflected from the adjacent anatomical airway structure.

22. 10. The system of claim 1, further comprising one or more pacing electrodes disposed on the expandable anchor, the one or more pacing electrodes configured to pace the blood vessel and elicit a physiological response from the patient when a phrenic nerve is located about the blood vessel.

23. 10. The system of claim 1, further comprising an expansion mechanism configured to apply sufficient force to an inner wall of the blood vessel to expand the blood vessel and stimulate baroreceptors within the blood vessel.

24. 24. The system of claim 23, wherein the expansion mechanism comprises an expandable member configured to be expanded from a collapsed state to an expanded state, wherein in the expanded configuration, the expandable member applies the force to the interior wall of the blood vessel.

25. 24. The system of claim 23, wherein the expansion mechanism comprises a torque applying mechanism configured to bend an elongate shaft of the system within the blood vessel and apply the force to the inner wall of the blood vessel.

26. and a controller operably coupled to the one or more sensors configured to measure pressure in the blood vessel, the controller comprising: receiving first pressure information within the blood vessel from the one or more sensors at a first time; receiving second pressure information within the blood vessel from the one or more sensors at a second time while the expandable member is applying a first force to the interior wall to open the blood vessel; receiving third pressure information within the blood vessel from the one or more sensors at a third time after ultrasonic energy is emitted within the blood vessel via the ultrasonic transducer to reduce neural activity of nerves surrounding the blood vessel and during the expandable member applying a second force to the interior wall to open the blood vessel; comparing the second pressure information to the third pressure information to determine if the ultrasound energy is reducing neural activity of the nerve surrounding the blood vessel; 24. The system of claim 23, programmed to:

27. 27. The system of claim 26, wherein the second pressure information indicates a first pressure gradient between the pressure in the blood vessel while the first force is applied to the inner wall to open the blood vessel and a pre-opening pressure in the blood vessel associated with the first pressure information, and the third pressure information indicates a second pressure gradient between the pressure in the blood vessel while the second force is applied to the inner wall to open the blood vessel and a pre-opening pressure in the blood vessel associated with the first pressure information.

28. 28. The system of claim 27, wherein the ultrasound energy reduces neural activity of the nerve surrounding the blood vessel when the comparison of the second and third pressure information indicates that the second pressure gradient is less than the first pressure gradient by an amount greater than a predetermined threshold.

29. The system of claim 1 , further comprising one or more sensors configured to measure pressure in the blood vessel.

30. a transducer catheter having a lumen sized and shaped to receive the transducer shaft therein and a proximal region operably coupled to the handle, the transducer catheter being slidably disposed within the outer catheter; the transducer shaft and the transducer catheter are sealed to create a fluidly sealed cavity therebetween; At least one cable is disposed within the fluidly sealed cavity and provides electrical energy to the ultrasonic transducer for emitting ultrasonic energy. The system of claim 1 .

31. 31. The system of claim 30, wherein the handle is configured to be actuated to cause translational movement of the ultrasound transducer relative to the inner catheter and the outer catheter via the transducer shaft and the transducer catheter.

32. The system of claim 1 , wherein at least one of the inner catheter, the outer catheter, and the sheath comprises a guidewire port configured to receive the guidewire therethrough.

33. 2. The system of claim 1, further comprising one or more intravascular ultrasound (IVUS) transducers disposed on at least one of the inner catheter distal to the ultrasound transducer, the outer catheter between the ultrasound transducer and the proximal end of the expandable anchor, or the outer catheter proximal to the proximal end of the expandable anchor, the one or more IVUS transducers configured to generate data for detecting anatomical structures adjacent to the blood vessel within a field of view of the one or more IVUS transducers.

34. 2. The system of claim 1, further comprising a torque shaft, the torque shaft comprising a lumen sized and shaped to receive the inner catheter therein and a proximal region operably coupled to the handle, the torque shaft coupled to the ultrasound transducer and configured to be actuated to cause rotation of the ultrasound transducer relative to the inner catheter.

35. 35. The system of claim 34, wherein the one or more IVUS transducers comprise a shield configured to mask at least a portion of the one or more IVUS transducers.

36. 35. The system of claim 34, wherein the ultrasonic transducer comprises a plurality of transducer sections, each transducer section of the plurality of transducer sections configured to be independently operable to selectively emit ultrasonic energy.

37. 1. A system for reducing neural activity in a nerve surrounding a blood vessel of a patient, the system comprising: a catheter assembly comprising a proximal region operably coupled to a handle and a distal region sized and shaped to be positioned within the blood vessel, the distal region of the catheter assembly comprising an ablation device configured to be actuated to release energy within the blood vessel to reduce neural activity of nerves surrounding the blood vessel; an expansion mechanism configured to apply a force to an inner wall of the blood vessel sufficient to expand the blood vessel and stimulate baroreceptors within the blood vessel; one or more sensors configured to measure pressure within the blood vessel; A controller operably coupled to the one or more sensors, the controller comprising: receiving first pressure information within the blood vessel from the one or more sensors at a first time; receiving second pressure information within the blood vessel from the one or more sensors at a second time while the expansion mechanism is applying a first force to the interior wall to expand the blood vessel; receiving third pressure information within the blood vessel from the one or more sensors at a third time after ultrasonic energy is emitted within the blood vessel via the ultrasonic transducer to reduce neural activity of nerves surrounding the blood vessel and during the expansion mechanism applying a second force to the interior wall to expand the blood vessel; comparing the second pressure information to the third pressure information to determine if the ultrasound energy is reducing neural activity of the nerve surrounding the blood vessel; A controller programmed to A system comprising:

38. 38. The system of claim 37, wherein the expansion mechanism comprises an expandable member configured to expand from a collapsed state to an expanded state to apply the force to the interior wall of the blood vessel.

39. 38. The system of claim 37, wherein the expansion mechanism comprises a torque applying mechanism configured to bend a shaft of the catheter assembly within the blood vessel and apply the force to the inner wall of the blood vessel.

40. 38. The system of claim 37, further comprising an expandable anchor configured to transition between a collapsed delivery state and an expanded deployed state, wherein in the expanded deployed state, the expandable anchor centers the ablation device within the blood vessel.

41. 38. The system of claim 37, wherein the ablation device is configured to emit at least one of focused ultrasound, unfocused ultrasound, radio frequency, microwave, cryoenergy, laser, or pulsed field electroporation.

42. 1. A system for reducing neural activity in a nerve surrounding a pulmonary artery of a patient, the system comprising: A handle and an elongate shaft having a proximal region operably coupled to the handle and a distal region; an ultrasound transducer disposed on the distal region of the elongate shaft, the ultrasound transducer configured to be activated to emit ultrasound energy within the pulmonary artery to reduce neural activity of nerves surrounding the pulmonary artery; an expandable anchor disposed on the distal region of the elongate shaft, the expandable anchor configured to transition between a collapsed delivery state and an expanded deployed state, wherein in the expanded deployed state, the expandable anchor causes the ultrasound transducer to be centrally located within the pulmonary artery of the patient; A system comprising:

43. 43. The system of claim 42, wherein the expandable anchor comprises a plurality of struts having rounded edges configured to prevent injury to the pulmonary artery.

44. 43. The system of claim 42, further comprising a sheath having a lumen sized and shaped to slidably receive the elongate shaft and the expandable anchor in the collapsed delivery state therein, a distal region of the sheath having sufficient stiffness to facilitate transition of the expandable anchor from the expanded deployed state to the collapsed delivery state in response to movement of the distal region of the sheath relative to the expandable anchor without buckling the distal region of the sheath, and a proximal region of the sheath operably coupled to the handle.

45. 43. The system of claim 42, wherein the ultrasound transducer is configured to emit the ultrasound energy within a main pulmonary artery branch, a right pulmonary artery branch, or a left pulmonary artery branch, or any combination thereof.

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