Tissue treatment system and method of controlling sonication based on sensed bioimpedance

Abstract

A tissue treatment catheter (102) has a catheter shaft (202), an energy delivery device (208) mounted on the catheter shaft (202) and configured to deliver energy to a target tissue (302), and an expandable member (112) mounted on the catheter shaft (202). The expandable member (112) has an outer surface (318) surrounding the energy delivery device (208). The expandable member (112) includes a plurality of electrodes (320) on the outer surface (318). The plurality of electrodes (320) is configured to probe the target tissue (302) at depth.

Description

POMD00004630SECWQ01 PATENTTISSUE TREATMENT SYSTEM AND METHOD OF CONTROLLING SONICATION BASED ON SENSED BIOIMPEDANCEPRIORITY

[0001] This application claims the benefit of priority to U.S. Provisional Application Nos. 63 / 733,979, filed December 13, 2024, of which is incorporated herein by reference in its entirety to provide continuity of disclosure.FIELD OF INVENTION

[0002] This application relates generally to medical apparatuses, systems, and methods that deliver energy to target an anatomical location of a subject. More specifically, this application relates to apparatuses, systems, and methods for the treatment of tissue, such as nerve tissue, using ultrasound energy.BACKGROUND

[0003] High blood pressure, also known as hypertension, commonly affects adults. Left untreated, hypertension can result in renal disease, arrhythmias, and heart failure. In recent years, the treatment of hypertension has focused on interventional approaches to inactivate the renal nerves surrounding a renal artery. Autonomic nerves tend to follow blood vessels to the organs that they innervate. Intraluminal devices, such as catheters, may reach specific structures, such as the renal nerves, which are proximate to the lumens in which the catheters travel. Accordingly, catheter-based systems can deliver energy from within the lumens to denervate the renal nerves in or in proximity to the vessel walls.

[0004] One approach to renal denervation uses radio frequency (RF) energy. The RF energy is delivered to a catheter having multiple electrodes placed against the intima of the renal artery to create an electrical field in the vessel wall and surrounding tissue. The electrical field results in resistive (ohmic) heating of the tissue to ablate the tissue and the renal nerve passing through that tissue. To treat all the renal nerves surrounding the renal arteries, the RF electrodes are repositioned several times around the inside of the renal artery.SUMMARY

[0005] According to an aspect of the present disclosure, a tissue treatment catheter is provided. The tissue treatment catheter includes a catheter shaft, an energy delivery devicemounted on the catheter shaft and configured to deliver energy to a target tissue, and an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of electrodes on the outer surface. The plurality of electrodes is configured to probe the target tissue at depth.

[0006] According to another aspect of the present disclosure, a tissue treatment system is provided. The tissue treatment system includes a tissue treatment catheter including a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of electrodes on the outer surface. The plurality of electrodes is configured to probe the target tissue at depth. The tissue treatment system includes a controller coupled to the tissue treatment catheter. The controller comprises a processing device configured to drive the energy delivery device to deliver energy to a target tissue, sense an electrical signal from the plurality of electrodes, and determine, based on the sensed electrical signal, whether the target tissue is ablated by the delivered energy. The processing device may in particular be configured to determine, based on the sensed electrical signal, whether the target tissue is ablated by the delivered energy to a predetermined depth.

[0007] According to another aspect of the present disclosure, a method is provided. The method includes advancing a tissue treatment catheter to a target tissue. The tissue treatment catheter includes a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of electrodes on the outer surface. The method includes deploying the expandable member against the target tissue. The method includes driving the energy delivery device to deliver energy to the target tissue. The method includes sensing an electrical signal from the plurality of electrodes. The method includes determining, by a processing device of a controller coupled to the tissue treatment catheter, based on the sensed electrical signal, whether the target tissue is ablated by the ultrasonic energy, in particular ablated to a predetermined depth.

[0008] According to another aspect of the present disclosure, a method is provided. The method includes retrieving records from a storage unit configured to communicate with a processing device of a controller coupled to a tissue treatment catheter. The tissue treatment catheter includes a catheter shaft, an energy delivery device mounted on the catheter shaft, and2 POMD04630SEC_WO01an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of electrodes on the outer surface. The records are indicative of an electrical signal from the plurality of electrodes sensed by the processing device. The method includes determining, by the processing device and based on the records indicative of the sensed electrical signal, whether the target tissue is ablated by the energy, in particular ablated to a predetermined depth.

[0009] According to another aspect of the present disclosure, a tissue treatment catheter is provided. The tissue treatment catheter includes a catheter shaft, an energy delivery device mounted on the catheter shaft and configured to deliver energy to a target tissue, and an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of ring electrodes on the outer surface. The plurality of ring electrodes are spaced at least 3 mm apart from each other and are positioned longitudinally beyond proximal and distal ends of the energy delivery device.

[0010] According to another aspect of the present disclosure, a tissue treatment system is provided. The tissue treatment system includes a tissue treatment catheter including a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of electrodes on the outer surface. The tissue treatment system includes a controller coupled to the tissue treatment catheter. The controller comprises a processing device configured to measure impedance from the plurality of electrodes, inflate the expandable member based on the measured impedance, determine whether the expandable member is in opposition with a vessel wall based on the measured impedance, pre-cool the expandable member before energy delivery based on the measured impedance, deliver energy to a target tissue based on the measured impedance, and post-cool the expandable member after energy delivery based on the measured impedance.

[0011] According to another aspect of the present disclosure, a tissue treatment catheter is provided. The tissue treatment catheter includes a catheter shaft, an energy delivery device mounted on the catheter shaft and configured to deliver energy to a target tissue, and an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of electrodes on the outer surface. The plurality of electrodes is configured to sense an electrical3 POMD04630SEC_WO01signal indicative of a bioimpedance of the target tissue for determining whether the target tissue is ablated by the energy delivery device.

[0012] According to another aspect of the present disclosure, a tissue treatment system is provided. The tissue treatment system includes a tissue treatment catheter including a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft. The expandable member has an outer surface surrounding the energy delivery device. The expandable member includes a plurality of electrodes on the outer surface. The tissue treatment system includes a controller coupled to the tissue treatment catheter. The controller comprises a processing device configured to deliver a sensing signal to the plurality of electrodes at a first frequency, deliver a driving signal to the energy delivery device at a second frequency higher than the first frequency, sense an electrical signal from the plurality of electrodes indicative of a bioimpedance of a target tissue, and determine, based on a change in the bioimpedance, whether the target tissue is ablated by the energy delivery device.

[0013] According to another aspect of the present disclosure, a method of confirming tissue ablation is provided. The method includes measuring, by a controller coupled to a tissue treatment catheter, a baseline bioimpedance of a target tissue using a plurality of electrodes on an outer surface of an expandable member of the tissue treatment catheter. The expandable member surrounds an energy delivery device of the tissue treatment catheter. The method includes delivering energy from the energy delivery device to the target tissue. The method includes measuring, by the controller, a post-treatment bioimpedance of the target tissue using the plurality of electrodes. The method includes determining, by the controller, that the target tissue is ablated when a difference between the baseline bioimpedance and the post-treatment bioimpedance meets a threshold criteria.

[0014] The foregoing general description of the illustrative embodiments and the following detailed description thereof are merely exemplary aspects of the teachings of this disclosure and are not restrictive.

[0015] Each of the method aspects presented herein can also be implemented by a computer program product comprising program code portions (e.g., instructions) configuring one or more processers (e.g., of a controller) of a tissue treatment system to implement the method aspect.

[0016] In each of the aspects presented herein, the energy delivery device may selected from an ultrasound transducer, one or more antennas, and one or more lasers.4 POMD04630SEC_WO01BRIEF DESCRIPTION OF FIGURES

[0017] Non-limiting and non-exhaustive examples are described with reference to the following figures.

[0018] FIG. 1 is a perspective view of a tissue treatment system 100, in accordance with an embodiment.

[0019] FIG. 2 is a perspective view of a tissue treatment catheter 102, in accordance with an embodiment.

[0020] FIG. 3 is a perspective view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen, in accordance with an embodiment.

[0021] FIG. 4 is a longitudinal cross-sectional view of a distal portion of a tissue treatment catheter 102, in accordance with an embodiment.

[0022] FIG. 5 is a block diagram of a tissue treatment generator 120 of a tissue treatment system 100, in accordance with an embodiment.

[0023] FIG. 6 is a flowchart of a method of controlling sonication based on sensed bioimpedance, in accordance with an embodiment.

[0024] FIG. 7A is a perspective view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen, in accordance with an embodiment.

[0025] FIG. 7B is a perspective view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen, in accordance with an embodiment.

[0026] FIG. 8 is a perspective view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen with input electrodes 702 and output electrodes 802, in accordance with an embodiment.

[0027] FIG. 9 A is a schematic view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen, in accordance with an embodiment.

[0028] FIG. 9B is a schematic view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen, in accordance with an embodiment.

[0029] FIG. 10 is a block diagram of a treatment confirmation system 100, in accordance with an embodiment.5 POMD04630SEC_WO01

[0030] FIG. 11 is a flowchart of a method 900 of positioning a catheter at a target site, in accordance with an embodiment.

[0031] FIG. 12 is a flowchart of a method 1000 of ablating target tissue by ultrasonic energy, in accordance with an embodiment.

[0032] FIG. 13 is a diagram showing determined impedance over time during tissue ablation, in accordance with an embodiment.

[0033] FIGS. 14A to 14C are schematic views of a coaxial cable 1100 connecting respective antennas for microwave thermal ablation to a generator, in accordance with respective embodiments.

[0034] FIG. 15 is a schematic view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen, in accordance with an embodiment.

[0035] FIGS. 16A to 16C are schematic views of different distal portions of a tissue treatment catheter 102 delivered into a body lumen, in accordance with respective embodiments.

[0036] FIG. 17 is a flowchart of a method 1700 of automating a tissue treatment procedure based on sensed impedance, in accordance with an embodiment.DETAIEED DESCRIPTION

[0037] The following description sets forth exemplary aspects of the present disclosure. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure. Rather, the description also encompasses combinations and modifications to those exemplary aspects described herein.

[0038] Many of the problems associated with RF systems are solved by a system having an ultrasound transducer that emits one or more therapeutic doses of unfocused ultrasound energy. The ultrasound transducer can be mounted at a distal end of catheter, and the unfocused ultrasound energy can heat tissue adjacent to a body lumen within which the catheter (and the transducer) is disposed. Such unfocused ultrasound energy may, for example, ablate target nerves surrounding the body lumen, without damaging non-target tissue such as the inner lining of the body lumen or unintended organs outside of the body lumen. The unfocused ultrasound energy system may also include a balloon mounted at the distal end of the catheter around the ultrasound transducer. A cooling fluid can be circulated through the balloon to cool the body lumen during ultrasound energy delivery. Such a design enables creation of one or more6 PGMD04630SEC_WG01ablation zones sufficient to achieve long-term nerve inactivation at different locations around the circumference of the blood vessel.

[0039] Systems that use unfocused ultrasound energy to treat tissue, and methods of using the same, are provided herein. In certain embodiments, acoustic-based tissue treatment transducers, apparatuses, systems, and portions thereof, are provided. The systems may be catheter-based. The systems may be delivered intraluminally (e.g., intravascularly) so as to place a transducer within a target anatomical region of the subject, for example, within a suitable body lumen such as a blood vessel. Once properly positioned within the target anatomical region, the transducer can be activated to deliver unfocused ultrasonic energy radially outward so as to suitably heat, and thus treat, tissue within the target anatomical region. The transducer or piezoelectric material can be activated at a frequency, duration, and energy level suitable for treating the ablation target, e.g., the targeted tissue. In one nonlimiting example, unfocused ultrasonic energy generated by the transducer or piezoelectric material or radio frequency (RF) energy transmitted by the electrodes may target select nerve tissue of the subject, and may heat such tissue in such a manner as to neuromodulate (e.g., fully or partially ablate, necrose, or stimulate) the nerve tissue.

[0040] Neuromodulating renal nerves may be used to treat various conditions, e.g., hypertension, chronic kidney disease, atrial fibrillation, autonomic nervous system for use in treating a variety of medical conditions, arrhythmia, heart failure, end stage renal disease, myocardial infarction, anxiety, contrast nephropathy, diabetes, metabolic disorder, and insulin resistance, etc. It should be appreciated, however, that tissue treatment catheters suitably may be used to treat other nerves and conditions, e.g., sympathetic nerves of the hepatic plexus within a hepatic artery responsible for blood glucose levels important to treating diabetes, or any suitable tissue, e.g., heart tissue triggering an abnormal heart rhythm, and is not limited to use in treating (e.g., neuromodulating) renal nerve tissue. In another example, a tissue treatment catheter is used to ablate sympathetic nerves of the renal arteries and a hepatic artery to treat diabetes or other metabolic disorders. In certain embodiments, the tissue treatment catheters are used to treat an autoimmune and / or inflammatory condition, such as rheumatoid arthritis, sepsis, Crohn’s disease, ulcerative colitis, and / or gastrointestinal motility disorders by neuromodulating sympathetic nerves within one or more of a splenic artery, celiac trunk, superior or inferior mesenteric artery. In certain embodiments, the tissue treatment catheter is used to ablate nerve fibers in the celiac ganglion and / or renal arteries to treat hypertension. In certain embodiments, the transducers are used to treat pain, such as pain associated with7 POMD04630SEC_WO01pancreatic cancer, by, e.g., neuromodulating nerves that innervate the pancreas. Ultrasound or RF energy may also be used to ablate nerves of both the pulmonary vein and the renal arteries to treat atrial fibrillation. In other examples, ultrasound or RF energy may additionally or alternatively be used to ablate nerves innervating a carotid body in order to treat hypertension and / or chronic kidney disease.

[0041] In various embodiments, description is made with reference to the figures. However, certain embodiments may be practiced without one or more of these specific details, or in combination with other known methods and configurations. In the following description, numerous specific details are set forth, such as specific configurations, dimensions, and processes, in order to provide a thorough understanding of the embodiments. In other instances, well-known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the description. Reference throughout this specification to “one embodiment,” “an embodiment,” or the like, means that a particular feature, structure, configuration, or characteristic described is included in at least one embodiment. Thus, the appearance of the phrase “one embodiment,” “an embodiment,” or the like, in various places throughout this specification are not necessarily referring to the same embodiment. Furthermore, the particular features, structures, configurations, or characteristics may be combined in any suitable manner in one or more embodiments.

[0042] The use of relative terms throughout the description may denote a relative position or direction. For example, “distal” may indicate a first direction relative to a reference point, such as a user. Similarly, “proximal” may indicate a second direction relative to the reference point, opposite to the first direction. Such terms are provided to establish relative frames of reference, however, and are not intended to limit the use or orientation of tissue treatment system components, e.g., a tissue treatment catheter, to a specific configuration described in the various embodiments below.

[0043] Existing hypertension treatment systems include generators to generate and deliver energy, e.g., RF or ultrasound energy. The treatment systems may also include components that engage with the generators to facilitate treatment. For example, a catheter-based intraluminal device can be coupled to a generator to deliver the energy to target tissue and thereby ablate the target tissue. Tissue ablation, however, is typically not detected by existing hypertension treatment systems. More particularly, there is no feedback mechanism to monitor or confirm that tissue ablation has occurred. Accordingly, tissue treatment systems used to8 POMD04630SEC_WO01deliver energy to target tissue would benefit from functionality allowing for monitoring of ablation progress and / or confirmation of effective tissue treatment by tissue ablation.

[0044] In an aspect, a tissue treatment system includes a tissue treatment catheter and a controller to deliver energy to target tissue based on sensed bioimpedance. The tissue treatment catheter includes an ultrasound transducer or other energy delivery device through an expandable member to the target tissue. Electrodes mounted on the expandable member can sense an electrical signal indicative of a target tissue characteristic. For example, the electrical signal can be used to measure bioimpedance of the target tissue to determine whether denervation of the target tissue is successfully achieved. The energy delivery can be controlled based on the sensed electrical signal and / or measured tissue characteristic. Accordingly, a user can confidently treat the target tissue with the tissue treatment system and have a clear understanding of the efficacy of the tissue treatment system.

[0045] Referring to FIG. 1 , a perspective view of a tissue treatment system is shown in accordance with an embodiment. A tissue treatment system 100 is shown as including a tissue treatment catheter 102 connected to a tissue treatment generator 120 by a connection cable 140. In certain embodiments, the tissue treatment catheter 102 includes an ultrasound transducer (FIG. 2) or other energy delivery device within an expandable member 109. For example, the expandable member 109 can include a balloon 112 containing the ultrasound transducer or other energy delivery device.

[0046] The tissue treatment system 100 can include a fluid reservoir 110 to store an inflation fluid 111. The inflation fluid 111 may be a cooling fluid. The tissue treatment system 100 can include, e.g., integrated within the generator 120, a fluid transfer unit 130 to transfer or move the inflation fluid 111 into and out of the balloon 112. More particularly, the fluid transfer unit 130 of the tissue treatment system 100 may deliver the inflation fluid 111 to the tissue treatment catheter 102. The tissue treatment system 100 may also include a cooling unit, e.g., integrated within the generator 120, to cool the inflation fluid 111. Accordingly, the inflation fluid 111 can be delivered to the balloon 112 by the fluid transfer unit 130 at a temperature below ambient temperature.

[0047] In an embodiment, the tissue treatment system 100 includes an energy delivery unit, e.g., an ultrasonic energy source as described below, configured to control activation, e.g., energize, the ultrasound transducer to deliver energy to a target tissue of the target9 PGMD04630SEC_WG01anatomy. More particularly, the ultrasonic energy source can deliver ultrasound energy to the tissue treatment catheter 102, e.g., through the connection cable 140.

[0048] In the embodiment shown in FIG. 1, the generator 120 is connected to the tissue treatment catheter 102 through an inflation tubing 138 for fluid transfer. In certain embodiments, the generator 120 interfaces with the fluid transfer unit 130 to provide the inflation fluid 111 to the tissue treatment catheter 102 for selectively inflating and deflating the balloon 112. The balloon 112 can be made from, e.g., nylon, a polyimide film, a thermoplastic elastomer (such as those marked under the trademark PEBAX™), a medical-grade thermoplastic polyurethane elastomer (such as Pellethane®, Isothane®, or other suitable polymers or any combination thereof), but is not limited thereto.

[0049] Referring to FIG. 2, a perspective view of a tissue treatment catheter is shown in accordance with an embodiment. The tissue treatment catheter 102 of the tissue treatment system 100 can include a catheter shaft 202 having an elongated body extending from a proximal catheter end 204 to a distal catheter end 206. The expandable member 109, e.g., the balloon 112, may be mounted on the catheter shaft 202, e.g., at the distal catheter end 206. One or more energy transducers, such as an ultrasound transducer 208, may be mounted on the catheter shaft 202. For example, the ultrasound transducer 208 may be positioned on the catheter shaft 202 within an interior defined by the expandable member 109.

[0050] The catheter shaft 202 can define one or more lumens such as: fluid lumen(s) to deliver an inflation / cooling fluid to the balloon 112, cable lumen(s) to provide electrical cable passageways to deliver energy to the ultrasound transducer 208, and guidewire lumens for exchanging guidewires, etc. The lumen(s) may be connected to corresponding connectors and / or terminal features, such as at the proximal catheter end 204. For example, the fluid lumens may connect to one or more fluid ports 210, which receive inflation / cooling fluid from the fluid transfer unit 130 of the tissue treatment system 100. Similarly, the electrical cables can connect to an external connector 212, which receives energy from the generator 120 of the tissue treatment system 100 through the connection cable 140.

[0051] Referring to FIG. 3, a perspective view of a distal portion of a tissue treatment catheter delivered into a body lumen is shown in accordance with an embodiment. A distal portion of the tissue treatment catheter 102 may be inserted into a body lumen of a subject. The body lumen may be a vessel 300, e.g., a blood vessel such as a renal artery, which has a target tissue 302, e.g., tissue layers or nerves surrounding the body lumen. Accordingly, the vessel10 PGMD04630SEC_WG01300 can be a target vessel of an ablation procedure. More particularly, the target tissue 302, such as a nerve 303, can be an ablation target. The target tissue 302 can surround the body lumen. For example, the nerve 303 may run in and around the blood vessel 300, such as through an outer layer, e.g., adventitia layer, of the vessel.

[0052] The distal portion of the tissue treatment catheter 102 may include the ultrasound transducer 208, the balloon 112 filled with the inflation fluid 111, a catheter shaft 202, and / or a guide wire support tip 304 configured to receive a guide wire 306. The transducer 210 may be disposed partially or completely within the balloon 112, which may be inflated with the inflation fluid 111. The inflation fluid 111 can include a liquid. The liquid may have a relatively high, as compared to gases, thermal capacity. For example, the liquid may include water, dextrose, or saline, and have a corresponding heat capacity. When the inflation fluid 111 is transferred into an interior 308 of the balloon 112, e.g., through a fluid lumen of the tissue treatment catheter 102 that is in fluid communication with the interior, the balloon can inflate into contact with a vessel wall 310 of the blood vessel 300. The vessel wall 310, and / or the nerves 302 extending within and around the vessel wall, can be the target tissue, e.g., an ablation target. In certain embodiments, the transducer 208 may be used to output acoustic energy to ablate the ablation target. Accordingly, the inflation fluid 111 can act as a heat sink to absorb heat generated by the ultrasound transducer 208 and / or delivered to the ablation target from the ultrasound transducer.

[0053] In certain embodiments, e.g., suitable for renal denervation, the balloon 112 is inflated while inserted in the body lumen of the patient during a procedure at a working pressure of about 10 to about 30 psi using the inflation fluid 111. The balloon 112 may be or include a compliant, semi-compliant, or non-compliant medical balloon. The balloon 112 is sized for insertion in the body lumen and, in the case of insertion into the renal artery, for example, the balloon 112 may be selected from available sizes including outer diameters of 3.5, 4.2, 5, 6, 7, or 8 mm, but not limited thereto. When activated, the transducer 208 can deliver the acoustic energy to the vessel wall 310 of the target vessel 300. The delivered energy can ablate and raise a temperature of the ablation target. The cooling fluid within the balloon 112, however, can be static and absorb heat to passively cool the ablation target and protect the target tissue and the transducer 210. The target tissue may therefore be treated by the delivered acoustic energy.

[0054] It will be appreciated that the expandable member 109 can be the balloon 112, however, the expandable member 109 may alternatively include a scaffold, cage, or another11 POMD04630SEC_WO01articulable structure capable of expanding from a collapsed state to an expanded state. For example, the expandable member 109 can include interconnected struts that articulate when a compressive load is applied to the structure, causing a diameter of the structure to increase. Accordingly, a surface of the expandable structure can move outward into contact with the vessel wall 310. In any case, the expandable member 109 can perform the functions described below, including deploying into contact with the vessel wall 310 to allow several electrodes 320 to sense characteristics of the target tissue 302, e.g., a bioimpedance of the target tissue 302.

[0055] The expandable member 109 can include an outer surface 318. For example, the outer surface 318 can be an outward facing surface of the balloon 112 or an outward facing surface of interconnected struts. In any case, the outer surface 318 can support one or more electrodes 320 used to sense bioimpedance of the target tissue 302, as described below. More particularly, the expandable member 109 can have the outer surface 318 surrounding the ultrasound transducer 208, and several electrodes 320 can be mounted on the outer surface 318 radially outward from the transducer 208, relative to a longitudinal axis of the catheter shaft 202. The electrodes 320 can, when the outer surface 318 is expanded into apposition with the vessel wall 310, contact the vessel wall 310. Accordingly, the electrodes 320 can become positioned to deliver and sense an electrical signal useful for monitoring tissue impedance before, during, or after tissue ablation by the transducer 208, in a method of controlling sonication based on sensed bioimpedance, as described below.

[0056] Referring to FIG. 4, a longitudinal cross-sectional view of a distal portion of a tissue treatment catheter is shown in accordance with an embodiment. The ultrasound transducer 208 may include a cylindrical hollow tube made of a piezoelectric material 400 (e.g. , lead zirconate titanate (PZT), etc.), with inner and outer electrodes 402, 404 disposed on the inner and outer surfaces of the cylindrical tube, respectively. Such a cylindrical hollow tube of piezoelectric material 400 is an example of, and thus can be referred to as, a piezoelectric transducer body. The piezoelectric transducer body can have various other shapes and need not be hollow. In certain embodiments suitable, e.g., for renal denervation, the piezoelectric material 400, of which the piezoelectric transducer body is made, is lead zirconate titanate 8 (PZT8), which is also known as Navy III Piezo Material. Raw PZT transducers may be plated with layers of copper, nickel, and / or gold to create electrodes 320 on surfaces (e.g., the inner and outer surfaces) of the piezoelectric transducer body. Application of a voltage and alternating current across inner and outer electrodes 402, 404 causes the piezoelectric material 400 to12 PGMD04630SEC_WO01vibrate transverse to the longitudinal direction of the cylindrical tube and radially emit ultrasonic waves.

[0057] In an embodiment, the ultrasound transducer 208 can be positioned within the interior 308 of the balloon 112. The balloon 112 can have the interior 308 in fluid communication with a fluid lumen 406 of the catheter shaft 202. The fluid lumen 406 can be the inflation lumen used to convey cooling fluid from the fluidic port to the balloon 112. The fluid lumen 406 can convey cooling fluid into the interior 308 to cool the transducer 208 and the vessel wall 310 (through contact with the balloon 112) during a treatment process. More particularly, the balloon 112 can contain the transducer 208 within the interior 308 such that the transducer 208 and the balloon 112 is contacted and cooled by cooling fluid that passes into the interior 308 from the fluid lumen 406.

[0058] As shown in FIG. 4, the ultrasound transducer 208 can be generally supported via a backing member 408 or post. In certain embodiments, the backing member 408 comprises stainless steel coated with nickel and gold. Nickel can be used as a bonding material between the stainless steel and gold plating. In certain embodiments suitable, e.g. , for renal denervation, an outer diameter of the transducer 208 is about 1.5 mm, an inner diameter of the transducer 208 is about 1 mm, and the transducer 208 has a length of about 6 mm. Transducers 208 having other inner diameters, outer diameters, and lengths, and more generally dimensions and shapes, are also within the scope of the embodiments described herein. Further, it is noted that the drawings in the figures are not necessarily drawn to scale, and often are not drawn to scale.

[0059] In order to permit liquid cooling along both the inner and outer electrodes 404, the backing member 408 may include one or more stand-off assemblies 410. The stand-off assemblies 410 may define one or more annular openings through which cooling fluid may enter the space of the transducer 208 (which may be selectively insulated) between the backing member 408 and the inner electrode 402. Accordingly, the backing member 408 may serve as a fluid barrier between the cooling fluid circulated within the balloon 112 and the lumen of the backing member 408 that receives the guidewire 306.

[0060] In accordance with certain embodiments, the stand-off assemblies 410 are electrically conductive, so as to electrically couple the inner electrode 402 of the ultrasound transducer 208 to the backing member 408. One or more conductors of the electrical cabling may be electrically coupled to the backing member 408. Thus, as the controller is activated, current may be delivered from the electrical cabling to the inner electrode 402 of the ultrasound13 POMD04630SEC_WO01transducer 208 via the backing member 408 and the stand-off assemblies 410, which advantageously eliminates the need to couple the cabling directly to the inner electrode 402 of the transducer 208. In other embodiments, the backing member 408 and the stand-off assemblies 410 are made of one or more electrical insulator material(s), or if made of an electrically conductive material(s) are coated with one or more electrical insulator material(s). In certain embodiments, one or more electrical conductors of the cabling are directly coupled (e.g., soldered) to the inner electrode 402 of the transducer 208.

[0061] The backing member 408 may have an isolation tube 420 disposed along its interior surface so as to prevent or reduce the likelihood of electrical conduction between the guidewire 306 and the backing member 408, for use in embodiments where such an electrical conduction is not desired. The isolation tube 420 can be formed of a non-electrically conductive material e.g., a polymer, such as polyimide), which can also be referred to as an electrical insulator. As illustrated in FIG. 4, the isolation tube 420 may extend through the lumen of the backing member 408 within the transducer 208 toward the catheter tip. In this manner, the ultrasound transducer 208 is mounted on the catheter shaft 202. More particularly, the isolation tube 420 can be an inner member of the catheter shaft 202, and the transducer 208 can be mounted on the inner member. The inner member can extend through an outer member that contains the fluid lumen 406. More particularly, the fluid lumen 406 may be a lumen between the outer member and the inner member.

[0062] The balloon 112 can be mounted on the catheter shaft 202 such that the balloon contains the ultrasound transducer 208 and the interior 308 of the balloon 112 is in fluid communication with the fluid lumen 406. For example, the outer surface 318 of the balloon 112 can surround the transducer 208. The balloon interior 308 can be a fluid chamber formed by seals between the balloon 112 and the catheter shaft 202. More particularly, the balloon 112 can include a distal balloon neck 422 mounted on the guidewire support tip 304 of the catheter shaft 202, and a proximal balloon neck 424 mounted on the outer member of the catheter shaft 202. The balloon necks may be sealed against the respective catheter shaft components to form a fluid chamber within the interior 308 longitudinally between the balloon necks. Each of the balloon necks can include respective ends of the balloon 112. For example, the distal balloon neck 422 can have a distal end of the balloon 112. Similarly, the proximal balloon neck 424 can have a proximal end of the balloon 112. The balloon necks 422, 424 can be bonded to or otherwise joined with the catheter shaft components, and thus, an interior14 POMD04630SEC_WO01surface of the balloon necks can be a same dimension as the components, e.g. , an outer diameter of the catheter tip or an outer diameter of the outer member.

[0063] The balloon 112 can include a balloon body 430 longitudinally between the balloon necks. The balloon body 430 can be a working section of the balloon 112. More particularly, the balloon body 430 may be a portion of the balloon 112 that has a largest diameter when the balloon 112 is inflated by cooling fluid. The balloon body 430 can be a portion of the balloon 112 that apposes the vessel wall 310 when such inflation is performed with the balloon 112 positioned within the target vessel 300.

[0064] The balloon body 430 can extend longitudinally between a proximal body end 432 and a distal body end 434. The body ends can define a length of the balloon body 430. The length may alternatively be defined as a section of the balloon 112 that, when the balloon 112 is inflated within the target vessel 300, is apposed to the vessel wall 310. The balloon body 430 may be defined independently from the target vessel 300 as being a section of the balloon 112 that, when the balloon 112 is inflated to a nominal inflation diameter, has a diameter greater than or equal to 95% of the nominal diameter.

[0065] The balloon 112 can include balloon shoulders extending between the balloon body 430 and respective balloon necks. In an embodiment, a distal balloon shoulder 436 extends from the distal balloon neck 422 to the balloon body 430. Similarly, a proximal balloon shoulder 438 extends from the proximal balloon neck 424 to the balloon body 430. The balloon shoulders 436, 438 may be portions of the balloon 112 that slope radially outward to the balloon body 430 when the balloon 112 is inflated within the target vessel 300. The balloon shoulders 436, 438 may be defined by inflection points between the various balloon sections. More particularly, an inflection point may be identified at which a slope of the balloon shoulder substantially decreases from a substantially outward direction to a substantially longitudinal direction. The balloon shoulders 436, 438 may also be defined in relation to the target vessel 300 or the nominal inflation diameter of the balloon 112. For example, the balloon shoulders 436, 438 may be sections of the balloon 112 that do not contact the vessel wall 310 when the balloon 112 is inflated within the target vessel 300. Alternatively, the balloon shoulders 436, 438 may be sections of the balloon 112 that have a diameter of 95% or less than the nominal inflation diameter of the balloon 112.

[0066] The several electrodes 320 can be located on the balloon body 430 of the balloon 112. For example, each of the electrodes 320 can be located longitudinally between the distal15 POMD04630SEC_WO01balloon shoulder 436 and the proximal balloon shoulder 438 to ensure that the electrodes 320 contact the vessel wall 310 when the balloon 112 is inflated to appose the vessel wall 310. As described below, an electrical signal may therefore pass from one of the electrodes 320 to another of the electrodes 320, through the target tissue 302. The electrodes 320 may be ring electrodes, as shown in FIG. 3. For example, one or more of a proximal electrode 470 and a distal electrode 472 can be ring electrodes that extend circumferentially around the outer surface 318 of the balloon 112. Cross-sections of the ring electrodes are shown in FIG. 4, and it will be appreciated that the section of the proximal electrode 470 can be continuous around the balloon circumference. Similarly, the distal electrode 470 can include a ring electrode continuously around the circumference. The ring electrodes can be longitudinally separated from each other along the balloon body 430.

[0067] Ring electrodes 320 are provided by way of example; however, the electrodes 320 may have other form factors. For example, the proximal electrode 320 and the distal electrode 320 can include discrete electrical pads. The pads may, for example, be longitudinally aligned along the outer surface 318 of the balloon 112 such that electrical current passing between the electrodes 320 travels in a longitudinal direction through the target tissue 302. Such electrode pads may be arranged as a broken ring or rings, as an array, or in any other suitable configuration.

[0068] The electrodes 320, whether structured as ring electrodes 320, electrical pads, or other form factors, can be fabricated and mounted on the outer surface 318 in a variety of ways. For example, the electrodes 320 may be applied using a metal deposition process to build the ring or pad structures on the balloon 112 surface. Alternatively, the conductive structures can be fabricated and then bonded to the outer surface 318 using an adhesive.

[0069] Notably, a portion of the balloon 112 can be electrically insulative to reduce a likelihood that electrical current will pass between the electrodes 320 through the balloon 112. For example, the various balloon 112 materials described above can have dielectric strengths that insulate against an electrical path passing through the balloon 112 from a proximal electrode 320 to a distal electrode 320. Isolating the electrical pathway may include insulating the pathway from the vessel 300 lumen. For example, by positioning the electrodes 320 within a length of the balloon body 430, e.g., on the working section, the electrodes 320 can be sandwiched between the balloon 112 and the vessel wall 310 when the balloon 112 is inflated. The balloon 112 can seal against the vessel wall 310 around the electrodes 320. Therefore, the electrical signal may not pass radially inward from the vessel wall 310 into16 PGMD04630SEC_WO01the vessel 300 lumen, which is blocked by the balloon 112. Accordingly, the insulative balloon 112 can reduce a likelihood of electrical path leakage that could degrade the electrical signal sensed to determine the bioimpedance of the target tissue 302.

[0070] Referring to FIG. 5, a block diagram of a tissue treatment generator 120 of a tissue treatment system 100 is shown in accordance with an embodiment. The block diagram represents an example implementation of the tissue treatment generator 120, which was introduced above. The generator 120 is shown as including a controller 502 having one or more processing devices 504, a memory 506, a user interface 508, and an ultrasound excitation source 510, but can include additional and / or alternative components. While not specifically shown, a processing device 504 can be located on a control board, or more generally, a printed circuit board (PCB) along with additional circuitry of the generator. The processing device 504 can communicate with the memory 506, which can include a non-transitory computer- readable medium storing instructions. The processing device 504 can execute the instructions to cause the tissue treatment system 100 to perform methods, such as controlling sonication based on sensed bioimpedance.

[0071] The user interface 508 can interact with the processing device 504 to cause transmission of electrical signals at selected actuation frequencies to the ultrasound transducer 208 via wires of the connection cable 140 and the cabling that extends through the catheter shaft 202. These wires electrically couple the generator to the transducer 208 so that the generator can send electrical signals to the transducer 208, and receive electrical signals from the transducer 208. The processing device 504 can control the ultrasound excitation source 510 to control the amplitude and timing of the electrical signals so as to control the power level and duration of the ultrasound signals emitted by transducer 208. More generally, the generator 120 can control one or more ultrasound treatment parameters that are used to perform sonication. Accordingly, the controller 502 of the generator 120, which is coupled to the tissue treatment catheter 102, can drive the ultrasound transducer 208 to deliver ultrasonic energy to the target tissue 302.

[0072] In certain embodiments, the excitation source can also detect electrical signals generated by the transducer 208 and communicate such signals to the processing device 504 and / or circuitry of a control board. While the ultrasound excitation source 510 is shown as being part of the controller 502, it is also possible that the ultrasound excitation source 510 is external to the controller 502 while still being controlled by the controller 502, and more specifically, by the processing device 504 of the generator controller 502.17 PGMD04630SEC_WO01

[0073] The user interface 508 can include a touch screen and / or buttons, switches, etc., to allow for an operator (user) to enter patient data, select treatment parameters, view records stored on a storage / re trieval unit (not shown), and / or otherwise communicate with the processing device 504. The user interface 508 can include a voice-activated mechanism to enter patient data or may be able to communicate with additional equipment so that control of the generator is through a separate user interface 508, such as a wired or wireless remote control. In some embodiments, the user interface 508 is configured to receive operator-defined inputs, which can include, e.g., a duration of energy delivery, one or more other timing aspects of the energy delivery pulses (e.g., frequency, duty cycle, etc.), power, body lumen length, mode of operation, patient parameter, such as height and weight, and / or verification of artery diameter, or a combination thereof. Example modes of operation can include (but are not limited to): system initiation and set-up, catheter preparation, balloon inflation, verification of balloon apposition, pre-cooling, sonication, post-cooling, balloon deflation, and catheter removal, but are not limited thereto. In certain embodiments, the user interface 508 provides a graphical user interface (GUI) that instructs a user how to properly operate the treatment system. The user interface 508 can also be used to display treatment data for review and / or download, as well as to allow for software updates, and / or the like.

[0074] The generator 120 can also control a cooling fluid supply subsystem 520, which can include the fluid transfer unit 130 and fluid reservoir 110, and can also include components such as fluid pumps and / or the like. The cooling fluid supply subsystem 520 is fluidically coupled to one or more fluid lumens 406 within the catheter shaft 202 which in turn are fluidically coupled to the balloon 112. The cooling fluid supply subsystem 520 can be configured to circulate a cooling liquid through the catheter to the transducer 208 in the balloon 112. The cooling fluid supply subsystem 520 may include elements such as the fluid reservoir 110 for holding the cooling fluid, pumps, and / or a refrigerating device such as a coil (not shown), or the like for providing a supply of cooling fluid to the interior 308 space of the balloon 112 at a controlled temperature, desirably at or below body temperature. The processing device 504 interfaces with the cooling fluid supply subsystem 520 to control the flow of cooling fluid into and out of the balloon 112. For example, the processing device 504 can control motor control devices linked to drive motors associated with pumps for controlling the speed of operation of pumps.

[0075] Having described the tissue treatment system 100 above, a method of using the tissue treatment system 100 to control sonication based on sensed bioimpedance will now be18 PGMD04630SEC_WO01described. The human body comprises cells, which can be modeled as electrical components. For example, groups of cells can contain fluids, such as intracellular and extracellular fluids, and the fluids contain ions that can conduct electrical signals. The electrical characteristics of the groups of cells (tissue), e.g., a resistivity or capacitance of the tissue, can depend on a cellular makeup of the tissue. A bioimpedance of the tissue depends on such electrical characteristics, and can vary based on whether the tissue is muscle or fat, benign or malignant, alive or dead, etc. Measuring the bioimpedance can therefore be used to determine the quality of the tissue. For example, ablation can destroy or distort cells, altering the electrical behavior of the cells. Unablated tissue may have more intercellular or extracellular fluid than ablated tissue, and can have a correspondingly lower impedance than the ablated tissue. Accordingly, measuring the bioimpedance of tissue that is being sonicated can be used to determine whether ablation of the tissue has occurred.

[0076] As described below, the electrodes 320 of the tissue treatment catheter 102 can be controlled by the controller 502 to sense bioimpedance of the target tissue 302. The sensed bioimpedance can then be used by the controller 502 to adjust sonication of the target tissue 302. The method can be performed using a variety of electrode configurations, as illustrated in FIGS. 7-8. Accordingly, FIGS. 6-8 are described in combination below.

[0077] Referring to FIG. 6, a flowchart of a method of controlling sonication based on sensed bioimpedance is shown in accordance with an embodiment. At operation 602, the tissue treatment catheter 102 is advanced to the target tissue 302. The distal portion of the tissue treatment catheter 102 can be delivered over the guidewire 306 through the vessel 300 to the target tissue location, e.g., within a renal artery adjacent to the nerve 303 in or around the vessel wall 310. The tissue treatment catheter 102 can undergo a preparation cycle before or after being tracked to the target site. For example, the fluid lines of the catheter shaft 202, and optionally the balloon 112, can be evacuated and filled with the inflation fluid 111 in preparation for balloon inflation.

[0078] At operation 604, the expandable member 109 is deployed against the target tissue 302. Inflation fluid 111 can be delivered into the interior 308 of the balloon 112 to cause the balloon 112 to expand. Alternatively, a compressive force can be applied to a scaffold to cause the scaffold to expand (or the scaffold can self-expand). In any case, the electrodes 320 on the outer surface 318 of the expandable member 109 can contact the vessel wall 310. In an embodiment, the expandable member 109 is configured to isolate the electrodes 320 against the vessel wall 310. For example, the balloon 112 can seal the electrodes 320 against the vessel19 PGMD04630SEC_WO01wall 310 to limit the electrical pathway of an electrical signal traveling between the electrodes 320 to the target tissue 302 (and not to the blood flowing through the vessel lumen).

[0079] At operation 606, ultrasonic energy is delivered to the target tissue 302. More particularly, the controller 502 can drive the ultrasound transducer 208, e.g., under control of the processing device 504, to generate and deliver the ultrasonic energy radially outward into the target tissue 302. Driving parameters can be used by the controller 502 to operate the ultrasound transducer 208. For example, driving the ultrasound transducer 208 can include delivering a driving signal to the transducer 208 to cause sonication to begin. The driving signal may have a driving parameter. For example, the driving signal can have a frequency of 5 MHz or more. The MHz scale frequency can excite the transducer 208 to generate ultrasonic energy. The ultrasonic energy can propagate from the transducer 208 through the expandable member 109, e.g., the balloon 112, into the target tissue 302. The ultrasonic energy delivered by the transducer 208 is mechanical energy, e.g., a vibration, which is different from electromagnetic radiation that is a quantized radiative phenomenon at a frequency. The mechanical vibrations can produce tissue heating, and the tissue characteristics, e.g., bioimpedance, may change as a result of ablation caused by the application of ultrasonic energy to that tissue.

[0080] At operation 608, an electrical signal from the electrodes 320 of the tissue treatment catheter 102 is sensed. The electrical signal can have an electrical power of less than 10 mW, for example, and may be delivered as a direct current or alternating current signal over short pulses, e.g., 100 times per second. The electrode 320 configuration that allows for sensing may vary, as described below. More particularly, a number, orientation, and / or spacing of the electrodes 320 can be varied to influence the signal measurement.

[0081] Referring to FIG. 7 A, a perspective view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen is shown in accordance with an embodiment. The several electrodes 320 on the outer surface 318 can include two or more input electrodes 702. The electrodes 320 can be termed input electrodes 702 because the electrodes 320 can actively conduct an electrical signal 704 into the target tissue 302. More particularly, the electrical signal 704 can include an electrical current delivered to the target tissue 302 when the outer surface 318 is in contact with the vessel wall 310. Accordingly, the input electrodes 702 can conduct the electrical signal 704 through the target tissue 302 in contact with the outer surface 318. It will be appreciated that the delivery of the electrical current through the target tissue 302 allows the tissue to be probed at depth, and not just along an inner surface of the20 POMD04630SEC_WO01vessel wall 310 or within the blood of the vessel 300. More particularly, the electrical signal 704 can be measured to understand bioimpedance of deep tissue, such as the nerve 303 around the vessel 300.

[0082] As described above, the input electrodes 702 can be ring electrodes 320 extending circumferentially around the outer surface 318 of the balloon 112. The ring electrodes 320 can be spaced apart from each other by a distance along the balloon body 430, e.g., at least 3 mm apart, e.g., 3 to 8 mm, e.g. 6 mm apart. A sensed bioimpedance may correspond to the spacing. More particularly, the electrical current that flows between the two electrodes 702, 320 can result in a measured voltage between the spaced electrodes 702, 320, and the voltage can be measured, e.g., by the processing device 504 of the controller 502, to determine the bioimpedance as described below. The depth of the bioimpedance measurement depends on the spacing of the electrodes. For example, as illustrated in FIG. 7B, the transducer may be longer (resulting in a greater ablation depth / volume) and the ring electrodes 702, 320 may be further apart, resulting in a deeper impedance measurement.

[0083] Referring to FIG. 8, a perspective view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen is shown in accordance with an embodiment. The expandable member 109, e.g., the balloon 112, can have the two or more input electrodes 702 and, additionally, two or more output electrodes 802. The output electrodes 802 can be so- termed because, unlike the input electrodes 702, the output electrodes 802 may not actively conduct the electrical signal 704 into the target tissue 302. Rather, the output electrodes 802 can be located within the path of the electrical signal 704 to receive the signal only.

[0084] In an embodiment, the output electrodes 802 are positioned between the two or more input electrodes 702 to sense the electrical signal 704. For example, the output electrodes 802 can include ring electrodes 320 positioned longitudinally between the input electrodes 702. Accordingly, when the electrical signal 704 traverses the distance between a proximal input electrode 702 and a distal input electrode 702, e.g. , when the electrical signal 704 is input as an electrical signal 704 passing through the target tissue 302, the signal can pass a proximal output electrode 802 and then a distal output electrode 802. As in the embodiment of FIG. 7, the voltage across the output electrodes 802 corresponding to the electrical signal 704 can be measured. The measured voltage can be used to determine the bioimpedance of the target tissue 302, as described below.21 PGMD04630SEC_WO01

[0085] The expandable member 109 may have more than two output electrodes 802. Output electrodes 802 may segment the measurable area into several zones. For example, a medial output electrode (not shown) can be located between the proximal most output electrode 802 and the distalmost output electrode 802 to form two zones. A first zone can be a space between the proximal most output electrode 802 and the medial output electrode. A second zone can be a space between the medial output electrode and a distalmost output electrodes 802. The first zone can measure bioimpedance of, for example, a proximal portion of the target tissue 302. The second zone can measure bioimpedance of a distal portion of the target tissue 302. Accordingly, any number of output electrodes 802 may be used to measure different lengths of target tissue 302 along the vessel 300. The spacing of the output electrodes 802 can determine a spatial resolution of the bioimpedance measurements that are used to control sonication of the target tissue 302.

[0086] An advantage of having a combination of input electrodes 702 and output electrodes 802 is that the configuration separates the active electrodes from the sensing electrodes. Stable electrical current demands a high impedance set of source electrodes, and reliable measurement requires a low impedance set of measurement electrodes. Accordingly, the two or more input electrodes 702 can have a higher impedance than the two or more output electrodes 802 to provide a stable electrical signal 704 by the input electrode 702 and an accurate bioimpedance measurement by the output electrode 802.

[0087] Sensing the electrical signal 704 can include delivering several sensing signals of various frequencies. More particularly, the sensing signals delivered to the electrodes 320 and into the target tissue 302 can be electrical signals 704 having respective frequencies. The various frequencies can be in a kHz range. For example, the electrical signal 704 may be any frequency of 500 kHz or less.

[0088] Monitoring tissue impedance between the two ends of the expandable member 109, across the target tissue 302 and between the input electrodes 702, at several frequencies can provide confidence in the measurement by creating different data points that can be combined or analyzed to determine the bioimpedance. More particularly, several samples can be measured, e.g., at 2-5 different frequencies over the 500 kHz range, to obtain measurements corresponding to the bioimpedance. The different samples may be averaged or used to detect measurement outliers to statistically determine a bioimpedance value. Alternatively, the measurements at different frequencies can be used to solve for different unknown variables in the governing bioimpedance models to obtain the bioimpedance value. In any case, delivering22 POMD04630SEC_WO01and measuring several electrical signals 704 having discrete frequencies from direct current to 500 kHz can provide data to determine bioimpedance of the target tissue 302 for use in controlling sonication, as described below.

[0089] Notably, a frequency of the electrical signal 704 can differ from a frequency of the driving signal used to generate sonication. For example, as described above, the electrical signal 704 frequency may be less than 500 kHz and the driving signal may be 5 MHz or more. Each of the electrodes of the tissue treatment catheter 102, e.g., the electrodes of the transducer 208 and the electrodes 320 on the outer surface 318, can be electrically connected to wires that send or receive signals. The signals traveling through the wires may interfere with each other if they are overlapping. Accordingly, in an embodiment, the use of acoustic frequencies in the MHz range and electrical measurement frequencies in the kHz range can avoid cross-talk between signals that may otherwise cause inaccuracies in measurements.

[0090] At operation 610, the processing device 504 of the controller 502 determines, based on the sensed electrical signal 704, whether the target tissue 302 is ablated by the ultrasonic energy. Applying and sensing the electrical signal 704 can be used to observe how reactance of the tissue changes. More particularly, the electrical signal 704 can be used to determine bioimpedance, which can be used to identify tissue and understand how the tissue changes before and after ablation, e.g., as a lesion is formed. The measurement of bioimpedance can be made before, during, and / or after sonication.

[0091] In an embodiment, tissue properties can be measured using the electrical signal 704 sensed prior to sonication (operation 606). For example, the bioimpedance may be sensed and determined prior to delivering ultrasonic energy to the target tissue 302. The measured bioimpedance may be used as a baseline impedance value. The baseline impedance value can be used to determine an initial state of the tissue, e.g., a tissue type, temperature, density, etc. Subsequent bioimpedance measurements may be compared to the baseline impedance value to understand how the tissue has changed as a result of sonication.

[0092] In an embodiment, the tissue properties can be measured using the electrical signal 704 sensed during sonication (operation 606). More particularly, sensing the electrical signal 704 (operation 608) can be performed during driving the ultrasound transducer 208 (operation 606). The measured bioimpedance can therefore be representative of the target tissue 302 under sonication. Changes may be anticipated, as the tissue is heated and eventually23 POMD04630SEC_WO01ablated. Accordingly, the bioimpedance measurement taken during sonication can be used to control sonication.

[0093] Controlling sonication based on the measured bioimpedance can include adjusting the driving parameter, e.g., the frequency, time, voltage, etc. of the driving signal delivered to the transducer 208 by the controller 502. The adjustment may be based on the sensed electrical signal 704 to drive the ultrasound transducer 208 to form an ablated lesion. For example, sonication can continue until the target tissue 302 is ablated. Determining whether the target tissue 302 is ablated can include measuring the bioimpedance of the target tissue 302 and comparing the measured bioimpedance to a threshold criteria. For example, when the bioimpedance meets the threshold criteria, e.g., a predetermined impedance value indicative of ablation, the processing device 504 can determine that the target tissue 302 is ablated. The processing device 504 may then adjust, e.g., change or stop, sonication of the target tissue 302 in response to the determination that ablation is successfully achieved.

[0094] A determination of ablation may alternatively be made based on a change in the bioimpedance. For example, determining whether the target tissue 302 is ablated can include measuring a first impedance prior to driving the ultrasound transducer 208 (measuring the baseline impedance value) and then measuring a second impedance during or after driving the ultrasound transducer 208 (a second bioimpedance value). A difference between the second bioimpedance value and the baseline impedance value can be determined by the processing device 504. In an embodiment, when the difference between the first impedance value and the second impedance value meets a threshold criteria, e.g., a predetermined difference, then the processing device 504 can determine that the target tissue 302 is ablated. Accordingly, the controller 502 can adjust sonication, e.g., by changing or stopping sonication.

[0095] In an embodiment, the tissue properties can be measured using the electrical signal 704 sensed after sonication (operation 606). Measuring after sonication can include measuring during sonication, e.g., after sonication begins. Alternatively, sonication may be intermittently paused to allow for measurements to be taken when the transducer 208 is inactive. In any case, the measured bioimpedance can be used to control, e.g., resume, change, or stop, sonication of the target tissue 302 when ablation is determined to be successful based on the comparison of measured values to the threshold criteria.

[0096] The monitored impedance between the ends of the expandable member 109 can be used to determine whether ablation has occurred and to control sonication accordingly. The24 POMD04630SEC_WO01measurement may, however, be used to determine other characteristics. For example, the measured bioimpedance may correspond to a temperature of the target tissue 302, a water content of the target tissue 302, a density of the target tissue 302, or a confirmation that the balloon 112 is in contact with the target tissue 302. These characteristics may be determined and used to control sonication. More particularly, the generator can be controlled, based on bioimpedance analysis, to deliver ultrasound energy to the target tissue 302. When the desired characteristic, e.g., a predetermined tissue temperature, density, or ablative state, is achieved, sonication can be stopped.

[0097] Referring to FIG. 9A, a schematic view of a distal portion of a tissue treatment catheter 102 located in a vessel 300 such that a balloonl l2 abuts a target tissue 302 is shown. Two ring electrodes 320 located on the outer surface 318 of the balloon are configured to at least one of deliver and sense an electrical signal indicative of tissue impedance and thus usable for monitoring tissue impedance before, during, or after tissue ablation as described above. The balloon 112 is further configured to electrically insulate the electrodes 320 from fluid flowing in the vessel 300, when inflated. In other words, when pressed against the vessel wall, the balloon substantially prevents fluid in the vessel 300, i.e. blood, from reaching the electrodes 320. For example, the balloon 112 may be made of electrically nonconductive polymers. As a result, an electrical field may be generated in the target tissue 302 via the electrodes 320. Field lines of an exemplary electrical field that may be generated in the target tissue 302 using the electrodes 320 are indicated by the arrows. As can be seen, the schematically shown field lines extend through the target tissue 302 and not through the fluid in the vessel 300, in particular, since the balloon 112 electrically insulates the electrodes from the fluid in the vessel 300 (and also from fluid inside the balloon). As a result, the shown configuration allows to determine a bioimpedance of the target tissue 302 based on the sensed electrical signal as described above.

[0098] Referring to FIG. 9B , spacing electrodes 320 further apart will result in spaced field lines of an exemplary electrical field that may be generated in the target tissue 302 using the electrodes 320 penetrating a greater depth, as indicated by the arrows. The ring electrodes 320 may be positioned longitudinally beyond the proximal and distal ends of the ultrasound transducer 208 along the balloon body 430. In an embodiment, the ring electrodes 320 are spaced at least 3 mm apart from each other. Given this electrode spacing, the ultrasound transducer 208 may have a minimum length of 2 mm. The length of the ultrasound transducer 208 may be proportionate to the ablation depth achieved in the target tissue 302. For example, a longer ultrasound transducer 208 may result in deeper ablation of the target tissue 302, while25 PGMD04630SEC_WG01a shorter ultrasound transducer 208 may result in shallower ablation. In some embodiments, the transducer length may be selected to achieve ablation up to 6 mm in depth for treatment confirmation. In some embodiments, the energy delivery device has a length of up to 8 mm. In some embodiments, the energy delivery device has a length of between 3 mm and 8 mm. For example, an energy delivery device having a length of 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, or 8 mm may be selected based on the target ablation depth and the anatomy of the target vessel.

[0099] In certain embodiments, the target ablation, or lesion, for, e.g., renal denervation extends from an inner radius of one millimeter beyond the artery intimal surface to an outer radius of six millimeters beyond the artery intimal surface. Using a circumferential transducer, as disclosed herein, the lesion is circumferentially uniform and is approximately the length of the transducer (6mm) in the axial direction. The volume (V) for the target lesion can be represented by the following equation: V = nl(To — ) where 1 is the axial length of the lesion (approximately the length of the transducer) and n and r0are the inner and outer target lesion radii, respectively. If we define the difference between the inner and outer target lesion radii as rA= r0— Ti the volume can be rewritten as: V = nlrA+ 2nlrAri. In certain embodiments, the electrodes are placed proximal and distal to the transducer, and therefore the impedance of the entire volume of the ablation field (i.e., the entire impact volume) is measured.

[0100] The impedance measured between the ring electrodes 320 (as, e.g., illustrated in Fig. 13) may be determined in a circular fashion around the entire circumference of the balloon 112. The ring electrodes 320 measure impedance around the entire circumference simultaneously. In other embodiments, the impedance measurement may be performed in a rotational or sequential manner around the circumference. The impedance measured between the ring electrodes 320 on the outer surface 318 of the balloon 112 can be extrapolated to determine the impedance of the target tissue 302 at depth. Accordingly, the bioimpedance measurement may provide information regarding tissue characteristics beyond the inner surface of the vessel wall 310, such as the nerve 303 located in or around the adventitia layer of the vessel 300.

[0101] The ring electrodes 320 are positioned on the balloon 112 because the balloon 112 is electrically insulative. As described above, the balloon 112 may be made of electrically nonconductive polymers that insulate the electrodes 320 from fluid flowing in the vessel 300 and from fluid inside the balloon 112. By positioning the electrodes 320 on the insulative balloon 112, the electrical pathway of the electrical signal 704 is directed through the target26 POMD04630SEC_WO01tissue 302 rather than through blood in the vessel lumen or cooling fluid within the balloon interior 308. This configuration enables accurate bioimpedance measurement of the target tissue 302 at depth for treatment confirmation.

[0102] FIG. 10 is a block diagram of a treatment confirmation system 100, in accordance with an embodiment. The treatment confirmation system 100 comprises a controller 502 configured for controlling the generator 120 as shown and explained with reference to FIG. 5 herein (as explained above, the present disclosure is not limited to an ultrasound transducer as an energy delivery device, so that the generator 120 could also take other forms depending on the nature of the energy delivery device). The system 100 further comprises a processing device 504 configured to analyze sensed electrical signals for determining a bioimpedance of target tissue 302 as described herein. In the shown example, the bioimpedance analysis comprises data acquisition, i.e., sensing an electrical signal using the electrodes 320, 802. The sensed signals may be stored in a storage / re trieval unit (not shown) for later retrieval and analysis. The analysis of the acquired data, i.e., the determination of the bioimpedance of the target tissue 302 is performed by the processing device 504. The shown system 100 further comprises a user interface 508, e.g., a graphical user interface (GUI) or any display suited for information display. As described with reference to FIG.5, the user interface 508 can be used, e.g., to display treatment data for review and / or download, as well as to allow for software updates, and / or the like.

[0103] FIG. 11 is a flowchart of a method 900 of positioning a catheter 102 at a target site. The method 900 of positioning a catheter at a target site may be performed using a tissue treatment system 100 as described herein. In a first step 910 a catheter 102 of the system 100 is positioned within a vessel 300. In a second step 920, a balloon 112 of the system 100 is inflated as described herein, e.g., with reference to FIGS. 1 to 4. In a third step 930 the bioimpedance is measured, i.e. determined based on the sensed electrical signal as described above. In a fourth step 940, it is determined whether the impedance is an opposed impedance, i.e. whether the balloon 112 isolates the electrodes from the fluid in the vessel 300. For example, the determined impedance may be compared to one or more known impedance values indicative of an impedance through tissue and / or through fluid. In another example, the impedance may be monitored during inflation and the opposition of the balloon 112 may be determined based on a change in the monitored impedance. For example, the impedance may be indicative of a fluid impedance, when the balloon 112 fails to insulate the electrodes 320 from the fluid in the vessel 300. A progressing inflation of the balloon 112 may result in a27 PGMD04630SEC_WO01progressing insulation of the electrodes 320, and thus to a rise in the determined bioimpedance, until the balloon completely insulates the electrodes from the fluid in the vessel 300 and an “opposition” state is determined, as shown, e.g., in FIG. 13. In case the determined bioimpedance indicates that electrodes 320 are not isolated from the fluid in the vessel 300, the method may return to the second step 920 of (further) inflating the balloon. In a fifth step 950, the determined opposed bioimpedance may be compared to a predetermined opposed impedance, which may be an expected opposed bioimpedance of the target tissue 302 at the target site. In case the determined opposed bioimpedance is not within a target range of the expected opposed bioimpedance, i.e., the catheter is not located at the expected target site, the method may return to the first step 910, i.e., the catheter may be repositioned. In case the determined opposed bioimpedance is within the target range of the expected opposed bioimpedance, the catheter is determined to be located at the target site and the method may continue with treatment of the target tissue 302 at the target site.

[0104] FIG. 12 is a flowchart of a method 1000 of ablating target tissue by ultrasonic energy. In a first step 1010, a balloon 112 may be inflated to opposition, e.g., as described with reference to FIG. 11 above. In a second step, 1020, energy may be applied to the target tissue via the transducer 208, e.g., the target tissue may be sonicated via the transducer 208. Before, during and / or after the sonication, a bioimpedance of the target tissue 302 is determined and, optionally, displayed to, e.g., a surgeon or other medical staff as shown in the third step 1030 of method 1000. A temperature of the target tissue 302 may be associated with the bioimpedance of the target tissue 302, e.g., the higher the temperature of the target tissue, the lower the bioimpedance of the target tissue 302. Thus, alternatively or additionally to the bioimpedance, the temperature of the target tissue 302 may be determined based on the sensed electrical signal and may be displayed. In a fourth step 1040, the determined bioimpedance and / or the determined temperature may be compared to a target bioimpedance or target temperature. In case the determined bioimpedance or temperature has dropped to or below the respective target bioimpedance or temperature, or has fulfilled another thresholding condition, the method is completed and no further sonication is performed. Else, the method may return to the second step 1020 and further sonicate the target tissue 302.

[0105] FIG. 13 is a diagram showing the determined impedance over time during tissue ablation, e.g., as described with reference to FIG. 12. The determined, i.e. monitored, impedance rises during balloon inflation until an opposition state is determined. The impedance at the opposition state may be defined as a baseline impedance and may depend on at least one28 PGMD04630SEC_WG01of vessel size, blood conductivity, and periarterial tissue. The baseline impedance at the opposition state may be between 60 Ohm and 900 Ohm, for example. In the shown example, the baseline impedance at the opposition state is at ca. 290 Ohm. After inflation of the balloon 112, a cooling fluid can be circulated through the balloon for pre-cooling, i.e. cooling before sonication. Due to the cooling the impedance rises again. During sonication, tissue is ablated and the bioimpedance drops accordingly. In the shown example the target bioimpedance is 250 Ohm and the sonication is stopped when the determined bioimpedance drops to the target bioimpedance. After sonication, a post cooling may be applied, which may raise the bioimpedance again. As explained above, the baseline impedance at the opposition state may depend on a multitude of parameters, e.g., one or more of a vessel size, blood conductivity, and periarterial tissue. However, while the absolute values of the impedance may differ depending on the multitude of parameters, the general form of the impedance curve during ablation remains generally the same, i.e., the curve may only shift in the absolute values.

[0106] FIG. 14A is a schematic view of a coaxial cable 1100 connecting an antenna 1150 for microwave thermal ablation to a generator, i.e., a power source (not shown). The antenna 1150 may be used in addition to or instead of the ultrasound transducer 208 described herein. In other words, energy may be applied to the target tissue via the antenna 1150. The shown coaxial cable 1100 comprises multiple layers as explained in the following, wherein the layers are explained from the outermost to the innermost layer. The outermost layer of the cable 1100 is a cable jacket 1110. An outer conductor 1120 is located adjacent to the cable jacket 1110. A dielectric 1130 is located adjacent to the outer conductor 1120, and a center conductor 1140 is located adjacent to the dielectric 1130 so that the dielectric 1130 is arranged between the outer conductor 1120 and the center conductor 1140. An outer diameter of the coaxial cable 1100 may be between 0,5 mm and 3 mm, e.g., between 1 mm and 2 mm. The generator is configured to provide sufficient power for microwave radiation via the antenna 1150. For example, the power may be between 1W and 150W, e.g., between 5W and 120W. The antenna 1150 shown in FIG. 14A is a monopole antenna 1150 formed by the center conductor 1140 extending from the coaxial cable 1100. The monopole antenna 1150 may have a length between 1 mm and 15 mm, e.g., between 2 mm and 12 mm. Since the antenna 1150 is configured to radiate microwaves, the antenna 1150 may also be referred to as microwave radiating tip 1150. While the antenna 1150 shown in FIG. 14A is an exposed antenna, other variants may comprise an antenna wrapped in insulation or dielectric materials.29 PGMD04630SEC_WO01

[0107] FIGS. 14B and 14C show different exemplary antennas 1160, 1170 compared to FIG. 14A. FIG. 14B shows a dipole antenna 1160 having two segments of different shape. For example, the first segment of the dipole antenna 1160 may extend from the coaxial cable 1100 and may have a length between 0,2 mm and 3 mm, e.g., between 0,5 mm and 2 mm. The second segment of the dipole antenna 1160 may extend from the first segment and may have a length between 1 mm and 10 mm, e.g., between 2 mm and 8 mm. FIG 14C shows a dual slot antenna having two exposed sections separated by an insulated section, wherein the insulated section is wrapped on a dielectric 1130, an outer conductor 1120 and a cable jacket 1110, i.e., the insulated section may be formed analogous to the coaxial cable 1100. The separated sections may have a similar shape, e.g., may be formed by the center conductor 1140 extending from the coaxial cable 1100 and may each have a length between 0,2 mm and 3 mm, e.g., between 0,5 mm and 2 mm. Further antenna configurations that are not shown are contemplated, e.g., helical, triaxial, choked, or sleeved antennas. A suitable antenna may be selected based on the planned ablation, and patient data, e.g., diagnosis. Utilizing different antennas allows for a wide range of use cases. A typical microwave frequency that may be generated via any of the antennas may be between 800 Mhz and 3 GHz, e.g., between 945 Mhz and 2,45 GHz. A treatment duration may be between 1 s to 40 s, e.g., between 2s to 30s. In other words, microwaves may be irradiated for 1 s to 40 s, e.g., 2s to 30s.

[0108] FIG. 15 shows a schematic view of a distal portion of a tissue treatment catheter 102 delivered into a body lumen. The distal portion of the tissue treatment catheter 102 may comprise any one of the antennas 1150, 1160, 1170 described above. When an antenna 1150, 1160, 1170 is used for microwave thermal ablation, a balloon 112 as described herein may separate the antenna 1150 from a vessel 300 and center the antenna 1150 inside the vessel 300. Moreover, a cooling fluid may be circulated within the balloon 112. For example, (sterile) water, air, or Saline may be circulated to cool the antenna and endothelium. Sterile water absorbs less of the emitted microwaves compared to Saline, which provides better cooling compared thereto. In another variant, carbon dioxide, CO2, can be used for cooling. CO2 does not absorb microwaves. As a result, less heat is generated inside the balloon. Moreover, CO2 is safe for a human compared to other known cooling fluids.

[0109] FIGS. 16A to 16C are directed at further variants of respective distal portions 1200, 1300, 1400 of a tissue treatment catheter 102 delivered into a body lumen. Instead of an antenna 1150, 1160, 1170 as shown in Figs 14A to 14C, different lasers with respective tips 1210, 1310,30 PGMD04630SEC_WG011410 are utilized for ablating tissue. The laser tips 1210, 1310, 1410 may be used in addition to or instead of an ultrasound transducer 208 and / or an antenna 1150, 1160, 1170 as described herein. Similar to the antenna tips, fluid may be circulated in a balloon 112 for cooling the laser tips 1150, 1160, 1170. The lasers may be configured to emit light with wavelengths ranging between 200 nm and 1500 nm, e.g., between 300nm to 1200 nm. A longer wavelength generates less heat in water, and has better tissue penetration. In some variants, a laser configured to emit light with a wavelength of 1030nm or 1064nm may be used. FIGS. 16A and 16B each show a schematic representations of laser tips 1210, 1310 using a diffusor to spread the emitted light in 360 degrees. In these variants, the tissue surrounding the catheter can be irradiated without the need for rotating the laser tip 1210, 1310. FIG. 16C shows a schematic representation of a variant configured for directed irradiation of light. In particular the laser tip 1410 comprises a side opening configured to allow light to be emitted therefrom, i.e., in a direction defined by the side widow. In this variant, the laser tip 1410 may be rotated around a longitudinal axis of the catheter shaft to achieve circumferential ablation, i.e., ablation in 360 degrees.

[0110] In an aspect, the tissue treatment system 100 may be configured to automate the tissue treatment procedure based on sensed impedance. The controller 502 may execute an algorithm that measures impedance from the electrodes 320 and automatically determines which step of the procedure to execute based on the measured impedance. Referring to FIG. 17, a flowchart of a method 8700 of automating a tissue treatment procedure based on sensed impedance (see Fig. 13) is shown in accordance with an embodiment. The method 1700 may be performed by the processing device 504 of the controller 502 executing instructions stored in the memory 506.

[0111] At step 1710, the controller 502 measures impedance from the electrodes 320. The impedance measurement may be performed continuously, at predetermined intervals, or in response to a trigger event. The measured impedance may be compared to one or more threshold values or analyzed to detect changes indicative of tissue or procedural state.

[0112] At step 1720, the controller 502 inflates the balloon 112 based on the measured impedance. For example, the controller 502 may control the fluid transfer unit 130 to deliver inflation fluid 111 into the balloon 112. The controller 502 may monitor the impedance during inflation to detect when the balloon 112 contacts the vessel wall 310.31 PGMD04630SEC_WO01

[0113] At step 1730, the controller 502 determines whether the balloon 112 is in opposition with the vessel wall 310 based on the measured impedance. As described with reference to FIG. 13, the impedance may rise during balloon inflation until an opposition state is reached. The controller 502 may detect the opposition state by identifying when the impedance reaches a threshold value, when the rate of impedance change decreases below a threshold, or when the impedance stabilizes. If the balloon 112 is not in opposition, the method 1700 may return to step 1720 to further inflate the balloon 112.

[0114] At step 1740, the controller 502 pre-cools the balloon 112 before sonication (or alternative energy delivery) based on the measured impedance. The controller 502 may control the cooling fluid supply subsystem 520 to circulate cooling fluid through the balloon 112. The impedance may rise during pre-cooling as the tissue temperature decreases. The controller 502 may monitor the impedance to determine when pre-cooling is complete, for example, when the impedance reaches a pre-cooling threshold or when the impedance stabilizes at a baseline value.

[0115] At step 1750, the controller 502 sonicates the target tissue 302 based on the measured impedance. The controller 502 may drive the ultrasound transducer 208 to deliver ultrasonic energy to the target tissue 302. During sonication, the impedance may drop as the tissue is heated and ablated. The controller 502 may monitor the impedance to control sonication parameters, such as power, duration, or frequency (of course, the parameters may differ for other energy delivery devices). The controller 502 may determine that ablation is complete when the impedance drops to a target impedance value or when the impedance change meets a threshold criteria, as described above.

[0116] At step 1760, the controller 502 post-cools the balloon 112 after sonication based on the measured impedance. The controller 502 may continue to circulate cooling fluid through the balloon 112 after sonication is complete. The impedance may rise during post-cooling. The controller 502 may monitor the impedance to determine when post-cooling is complete, for example, when the impedance stabilizes or when a predetermined post-cooling duration has elapsed. Upon completion of post-cooling, the method 1700 may end, or the controller 502 may deflate the balloon 112 and reposition the catheter 102 for treatment at another location.

[0117] The automated method 1700 may provide several advantages. By using impedance measurements to control each step of the procedure, the controller 502 may reduce variability in treatment outcomes and reduce reliance on operator judgment. The controller 502 may32 PGMD04630SEC_WO01automatically adapt to patient-specific anatomy and tissue characteristics based on the measured impedance. The controller 502 may also provide real-time feedback to the operator via the user interface 508, displaying the current procedural step, measured impedance, and other relevant information.

[0118] Embodiments of a tissue treatment system are described above. More particularly, embodiments of the treatment system are described, either explicitly or implicitly. The following paragraphs summarize some of the described embodiments. More particularly, embodiments are described in the following enumerated example clauses.

[0119] Example Clause A: A tissue treatment catheter, may include: a catheter shaft; an ultrasound transducer mounted on the catheter shaft; and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the ultrasound transducer, and wherein the expandable member includes a plurality of electrodes on the outer surface.

[0120] Example Clause B: The tissue treatment catheter of Example Clause A, wherein the plurality of electrodes include two or more input electrodes to conduct an electrical signal through a target tissue in contact with the outer surface.

[0121] Example Clause C: The tissue treatment catheter of Example Clause A or Example Clause B, wherein the plurality of electrodes include two or more output electrodes positioned between the two or more input electrodes to sense the electrical signal.

[0122] Example Clause D: The tissue treatment catheter of any one of Example Clauses A-C, wherein the two or more input electrodes have a higher impedance than the two or more output electrodes.

[0123] Example Clause E: The tissue treatment catheter of any one of Example Clauses A-D, wherein the expandable member is a balloon, and wherein the plurality of electrodes include ring electrodes extending circumferentially around the outer surface of the balloon.

[0124] Example Clause F: The tissue treatment catheter of any one of Example Clauses A-E, wherein the plurality of electrodes are located on a balloon body of the balloon longitudinally between a distal balloon shoulder and a proximal balloon shoulder of the balloon.

[0125] Example Clause G: The tissue treatment catheter of any one of Example Clauses A-F, wherein the balloon body of the balloon is electrically insulative.33 PGMD04630SEC_WO01

[0126] Example Clause H: A tissue treatment system, may include: a tissue treatment catheter including a catheter shaft, an ultrasound transducer mounted on the catheter shaft, and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the ultrasound transducer, and wherein the expandable member includes a plurality of electrodes on the outer surface; and a controller coupled to the tissue treatment catheter, the controller may include a processing device to drive the ultrasound transducer to deliver ultrasonic energy to a target tissue, sense an electrical signal from the plurality of electrodes, and determine, based on the sensed electrical signal, whether the target tissue is ablated by the ultrasonic energy.

[0127] Example Clause I: The tissue treatment system of Example Clause H, wherein the expandable member is a balloon, and wherein the plurality of electrodes include ring electrodes extending circumferentially around the outer surface of the balloon.

[0128] Example Clause J: The tissue treatment system of Example Clause H or Example Clause I, wherein driving the ultrasound transducer includes delivering a driving signal having a first frequency of 5 MHz or more to the ultrasound transducer, and wherein the electrical signal has a second frequency of 500 kHz or less.

[0129] Example Clause K: The tissue treatment system of any one of Example Clauses H-J, wherein sensing the electrical signal includes delivering a plurality of sensing signals having respective frequencies to the plurality of electrodes.

[0130] Example Clause L: The tissue treatment system of any one of Example Clauses H-K, wherein determining whether the target tissue is ablated includes: measuring a bioimpedance of the target tissue, and determining the target tissue is ablated when the bioimpedance meets a threshold criteria.

[0131] Example Clause M: The tissue treatment system of any one of Example Clauses H-L, wherein determining whether the target tissue is ablated includes: measuring a first impedance prior to driving the ultrasound transducer, measuring a second impedance during or after driving the ultrasound transducer, and determining the target tissue is ablated when a difference between the first impedance and the second impedance meets a threshold criteria.

[0132] Example Clause N: The tissue treatment system of any one of Example Clauses H-M, wherein sensing the electrical signal is performed during driving the ultrasound transducer.34 POMD04630SEC_WO01

[0133] Example Clause O: The tissue treatment system of any one of Example Clauses H- N further may include adjusting, based on the sensed electrical signal a driving parameter used to drive the ultrasound transducer.

[0134] Example Clause P: A method, may include: advancing a tissue treatment catheter to a target tissue, wherein the tissue treatment catheter includes a catheter shaft, an ultrasound transducer mounted on the catheter shaft, and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the ultrasound transducer, and wherein the expandable member includes a plurality of electrodes on the outer surface; deploying the expandable member against the target tissue; driving the ultrasound transducer to deliver ultrasonic energy to the target tissue; sensing an electrical signal from the plurality of electrodes; and determining, by a processing device of a controller coupled to the tissue treatment catheter, based on the sensed electrical signal, whether the target tissue is ablated by the ultrasonic energy.

[0135] Example Clause Q: The method of Example Clause P, wherein the expandable member is a balloon, and wherein the plurality of electrodes include ring electrodes extending circumferentially around the outer surface of the balloon.

[0136] Example Clause R: The method of Example Clause P or Example Clause Q, wherein driving the ultrasound transducer includes delivering a driving signal having a first frequency of 5 MHz or more to the ultrasound transducer, and wherein the electrical signal has a second frequency of 500 kHz or less.

[0137] Example Clause S: The method of any one of Example Clauses P-R, wherein sensing the electrical signal includes delivering a plurality of sensing signals having respective frequencies to the plurality of electrodes.

[0138] Example Clause T: The method of any one of Example Clauses P-S, wherein determining whether the target tissue is ablated includes: measuring a bioimpedance of the target tissue, and determining the target tissue is ablated when the bioimpedance meets a threshold criteria.

[0139] Example Clause U: The method of any one of Example Clauses P-T, wherein determining whether the target tissue is ablated includes: measuring a first impedance prior to driving the ultrasound transducer, measuring a second impedance during or after driving the ultrasound transducer, and determining the target tissue is ablated when a difference between the first impedance and the second impedance meets a threshold criteria.35 POMD04630SEC_WO01

[0140] Example Clause V: The method of any one of Example Clauses P-U, wherein sensing the electrical signal is performed during driving the ultrasound transducer.

[0141] Example Clause W: The method of any one of Example Clauses P-V further may include adjusting, based on the sensed electrical signal, a driving parameter used to drive the ultrasonic energy.

[0142] In the foregoing specification, the present disclosure has been described with reference to specific exemplary embodiments thereof. It will be evident that various modifications may be made thereto without departing from the broader spirit and scope of the present disclosure as set forth in the following claims. The specification and drawings are, accordingly, to be regarded in an illustrative sense rather than a restrictive sense.

[0143] A number of implementations have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the disclosure. Accordingly, other implementations are within the scope of the following claims.36 POMD04630SEC_WO01

Claims

CLAIMS1. A tissue treatment catheter, comprising: a catheter shaft; an energy delivery device mounted on the catheter shaft and configured to deliver energy to a target tissue; and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, wherein the expandable member includes a plurality of electrodes on the outer surface, and wherein the plurality of electrodes is configured to probe the target tissue at depth.

2. The tissue treatment catheter of claim 1, wherein the plurality of electrodes include two or more input electrodes to conduct an electrical signal through the target tissue in contact with the outer surface.

3. The tissue treatment catheter of claim 2, wherein the plurality of electrodes include two or more output electrodes positioned between the two or more input electrodes to sense the electrical signal.

4. The tissue treatment catheter of any of claims 2 to 3, wherein the two or more input electrodes have a higher impedance than the two or more output electrodes.

5. The tissue treatment catheter of any of claims 1 to 4, wherein the expandable member is a balloon.

6. The tissue treatment catheter of claim 5, wherein: the plurality of electrodes include at least a first and a second ring electrode extending circumferentially around the outer surface of the balloon, wherein the first ring electrode is proximal to the energy delivery device, and the second ring electrode is distal to the energy delivery device.

7. The tissue treatment catheter of any of claims 5 to 6, wherein the plurality of electrodes is located on a balloon body of the balloon longitudinally between a distal balloon shoulder and a proximal balloon shoulder of the balloon, wherein, as an option, the energy delivery device is at least 3 mm long and, as a further option, the plurality of electrodes is configured to probe the target tissue at depth of at least 3 mm.37 POMD04630SEC_WO018. The tissue treatment catheter of any of claims 5 to 6, wherein the plurality of electrodes is located on a balloon body of the balloon longitudinally between a distal balloon shoulder and a proximal balloon shoulder of the balloon, as and option, the energy delivery device is 3 to 8 mm long and, as a further option, the plurality of electrodes is configured to probe the target tissue at depth of 3 to 8 mm.

9. The tissue treatment catheter of claim 7 or 8, wherein the balloon body of the balloon is electrically insulative.

10. The tissue treatment catheter of any of claims 1 to 9, wherein the energy delivery device is selected from an ultrasound transducer, one or more antennas, and one or more lasers.

11. A tissue treatment system, comprising: a tissue treatment catheter including a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, and wherein the expandable member includes a plurality of electrodes on the outer surface, and wherein the plurality of electrodes is configured to probe the target tissue at depth; and a controller coupled to the tissue treatment catheter, the controller comprising a processing device configured to drive the energy delivery device to deliver energy to a target tissue, sense an electrical signal from the plurality of electrodes, and determine, based on the sensed electrical signal, whether the target tissue is ablated by the delivered energy, in particular to a predetermined depth.

12. The tissue treatment system of claim 11, wherein the sensed electrical signal is indicative of a bioimpedance of deep tissue beyond an inner surface of a vessel wall that is in contact with the expandable member, and wherein determining whether the target tissue is ablated is based on the sensed bioimpedance.

13. The tissue treatment system of claim 12, wherein the controller is configured to control energy delivery based on the bioimpedance indicated by the sensed electrical signal.

14. The tissue treatment system of any of claims 11 to 13, wherein the expandable member is a balloon.38 POMD04630SEC_WO0115. The tissue treatment system of claim 14, wherein the plurality of electrodes include ring electrodes extending circumferentially around the outer surface of the balloon and wherein, as an option, the ring electrodes are at least 3 mm apart.

16. The tissue treatment system of any of claims 14 to 15, wherein the plurality of electrodes is located on a balloon body of the balloon longitudinally between a distal balloon shoulder and a proximal balloon shoulder of the balloon.

17. The tissue treatment system of claim 16, wherein the balloon body of the balloon is electrically insulative and wherein the processing device is further configured to determine, based on the sensed electrical signal, an impedance throughout an impact volume of the energy delivery device.

18. The tissue treatment system of any of claims 11 to 17, wherein the energy delivery device is an ultrasound transducer, and wherein the processing device is further configured to deliver a driving signal having a first frequency of 5 MHz or more to the ultrasound transducer, and wherein the electrical signal has a second frequency of 500 kHz or less.

19. The tissue treatment system of any of claims 11 to 18, wherein the processing device is further configured to deliver a plurality of sensing signals having respective frequencies to the plurality of electrodes.

20. A method, comprising: advancing a tissue treatment catheter to a target tissue, wherein the tissue treatment catheter includes a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, and wherein the expandable member includes a plurality of electrodes on the outer surface; deploying the expandable member against the target tissue; driving the energy delivery device to deliver energy to the target tissue throughout an impact volume; sensing an electrical signal from the plurality of electrodes; and determining, by a processing device of a controller coupled to the tissue treatment catheter, based on the sensed electrical signal, whether the target tissue is ablated to a predetermined depth by the energy.39 POMD04630SEC_WO0121. The method of claim 20, wherein the expandable member is a balloon.

22. The method of claim 21, wherein the plurality of electrodes include at least a first and a second ring electrode extending circumferentially around the outer surface of the balloon, wherein the first ring electrode is proximal the energy delivery device and wherein the second ring electrode is distal the energy delivery device.

23. The method of any of claims 21 to 22, wherein the plurality of electrodes are located on a balloon body of the balloon longitudinally between a distal balloon shoulder and a proximal balloon shoulder of the balloon.

24. The method of claim 23, wherein the balloon body of the balloon is electrically insulative.

25. The method of any of claims 20 to 24, wherein energy delivery device is an ultrasound transducer, and driving the ultrasound transducer includes delivering a driving signal having a first frequency of 5 MHz or more to the ultrasound transducer, and wherein the electrical signal has a second frequency of 500 kHz or less.

26. The method of any of claims 20 to 25, wherein sensing the electrical signal includes delivering a plurality of sensing signals having respective frequencies to the plurality of electrodes.

27. The method of any of claims 20 to 26, wherein determining whether the target tissue is ablated includes: measuring a bioimpedance of the target tissue throughout the impact volume; and determining the target tissue is ablated to the predetermined depth when the bioimpedance meets a threshold criteria.

28. The method of any of claims 20 to 27, wherein determining whether the target tissue is ablated to the predetermined depth includes: measuring a first impedance prior to driving the energy delivery device; measuring a second impedance during or after driving the energy delivery device; and determining the target tissue is ablated to the predetermined depth when a difference between the first impedance and the second impedance meets a threshold criteria.

29. The method of any of claims 20 to 28, wherein sensing the electrical signal is performed during driving the energy delivery device.40 POMD04630SEC_WO0130. The method of any of claims 20 to 29, further comprising adjusting, based on the sensed electrical signal, a driving parameter used to drive the energy.

31. A method, comprising : retrieving records from a storage unit configured to communicate with a processing device of a controller coupled to a tissue treatment catheter, wherein the tissue treatment catheter includes a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, and wherein the expandable member includes a plurality of electrodes on the outer surface, the records being indicative of an electrical signal from the plurality of electrodes sensed by the processing device; and determining, by the processing device and based on the records indicative of the sensed electrical signal, whether the target tissue is ablated, in particular to a predetermined depth, by the energy.

32. The method of claim 31, wherein the expandable member is a balloon and wherein the electrodes are ring electrodes spaced at least 3 mm apart.

33. The method of claim 32, wherein the ring electrodes extend circumferentially around the outer surface of the balloon 3 to 8 mm apart.

34. The method of any of claims 32 to 33, wherein the plurality of electrodes are located on a balloon body of the balloon longitudinally between a distal balloon shoulder and a proximal balloon shoulder of the balloon.

35. The method of claim 34, wherein the balloon body of the balloon is electrically insulative.

36. The method of any of claims 31 to 35, wherein the energy delivery device is an ultrasound transducer configured to be driven by a driving signal having a first frequency of 5 MHz or more, and wherein the electrical signal has a second frequency of 500 kHz or less.

37. The method of any of claims 31 to 36, wherein the electrical signal is sensed by the processing device by delivering a plurality of sensing signals having respective frequencies to the plurality of electrodes.

38. The method of any of claims 31 to 37, wherein determining whether the target tissue is ablated includes: determining, based on the records, a bioimpedance of the target tissue; and41 POMD04630SEC_WO01determining the target tissue is ablated when the bioimpedance meets a threshold criteria.

39. The method of any of claims 31 to 38, wherein determining whether the target tissue is ablated includes: determining a first impedance from a record recorded prior to driving the energy delivery device; determining a second impedance from a record recorded during or after driving the energy delivery device; and determining the target tissue is ablated when a difference between the first impedance and the second impedance meets a threshold criteria.

40. The method of any of claims 31 to 39, wherein the electrical signal is sensed by the processing device when the energy delivery device is driven.

41. The method of any of claims 31 to 40, further comprising triggering adjustment, based on the sensed electrical signal, of a driving parameter used to drive the energy delivery device.

42. The method of any of claims 20 to 41, further comprising: inflating the expandable member; detecting apposition with a wall of a body lumen by detecting impedance, and if one or more electrodes is not in apposition with the wall of the body lumen, further inflating the expandable member; using the expandable member to cool the wall of the body lumen pre-ablation; detecting whether the wall of the body lumen is cooled to a predetermined threshold pre-ablation by detecting impedance; using the expandable member to cool the wall of the body lumen post-ablation; detecting whether the wall of the body lumen is cooled to a predetermined threshold post-ablation by detecting impedance.

43. A tissue treatment catheter, comprising: a catheter shaft;42 POMD04630SEC_WO01an energy delivery device mounted on the catheter shaft and configured to deliver energy to a target tissue; and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, wherein the expandable member includes a plurality of ring electrodes on the outer surface, and wherein the plurality of ring electrodes are spaced at least 3 mm apart from each other and are positioned longitudinally beyond proximal and distal ends of the energy delivery device.

44. The tissue treatment catheter of claim 43, wherein the energy delivery device has a length of up to 8 mm.

45. The tissue treatment catheter of any of claims 43 to 44, wherein the energy delivery device has a length of between 3 mm and 8 mm.

46. The tissue treatment catheter of any of claims 43 to 45, wherein a length of the energy delivery device is proportionate to an ablation depth achieved in the target tissue.

47. The tissue treatment catheter of any of claims 43 to 46, wherein the energy delivery device is configured to achieve ablation up to 6 mm in depth.

48. The tissue treatment catheter of any of claims 43 to 47, wherein the expandable member is a balloon, and wherein the balloon is electrically insulative such that an electrical pathway between the plurality of ring electrodes is directed through the target tissue.

49. The tissue treatment catheter of any of claims 43 to 48, wherein an impedance measured between the plurality of ring electrodes is configured to be extrapolated to determine impedance of the target tissue at depth.

50. The tissue treatment catheter of any of claims 43 to 49, wherein the impedance measured between the plurality of ring electrodes provides information regarding tissue characteristics beyond an inner surface of a vessel wall in contact with the expandable member.

51. A tissue treatment system, comprising: a tissue treatment catheter including a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, and wherein the expandable member includes a plurality of electrodes on the outer surface spaced at least 3 mm apart; and43 POMD04630SEC_WO01a controller coupled to the tissue treatment catheter, the controller comprising a processing device configured to: measure impedance of the tissue throughout the impact volume of the energy delivery device from the plurality of electrodes; inflate the expandable member based on the measured impedance; determine whether the expandable member is in opposition with a vessel wall based on the measured impedance; pre-cool the expandable member before energy delivery based on the measured impedance; deliver energy to a target tissue based on the measured impedance; and post-cool the expandable member after energy delivery based on the measured impedance.

52. The tissue treatment system of claim 51, wherein the processing device is configured to continuously measure impedance during the procedure.

53. The tissue treatment system of any of claims 51 to 52, wherein the processing device is configured to determine the expandable member is in opposition with the vessel wall when the measured impedance reaches a threshold value or when a rate of impedance change decreases below a threshold.

54. The tissue treatment system of any of claims 51 to 53, wherein the processing device is configured to determine pre-cooling is complete when the measured impedance stabilizes at a baseline value.

55. The tissue treatment system of any of claims 51 to 54, wherein the processing device is configured to determine sonication is complete when the measured impedance drops to a target impedance value.

56. The tissue treatment system of any of claims 51 to 55, wherein the processing device is configured to automatically adapt energy delivery parameters based on the measured impedance.

57. The tissue treatment system of any of claims 51 to 56, wherein the controller further comprises a user interface configured to display the current procedural step and the measured impedance.

58. A tissue treatment catheter, comprising:44 POMD04630SEC_WO01a catheter shaft; an energy delivery device mounted on the catheter shaft and configured to deliver energy to a target tissue; and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, wherein the expandable member includes a plurality of electrodes on the outer surface, and wherein the plurality of electrodes is configured to sense an electrical signal indicative of a bioimpedance of the target tissue for determining whether the target tissue is ablated to a predetermined depth by the energy delivery device.

59. The tissue treatment catheter of claim 58, wherein the plurality of electrodes is configured to sense the electrical signal without transmitting ablative energy to the target tissue.

60. A tissue treatment system, comprising: a tissue treatment catheter including a catheter shaft, an energy delivery device mounted on the catheter shaft, and an expandable member mounted on the catheter shaft, wherein the expandable member has an outer surface surrounding the energy delivery device, and wherein the expandable member includes a plurality of electrodes on the outer surface; and a controller coupled to the tissue treatment catheter, the controller comprising a processing device configured to: deliver a sensing signal to the plurality of electrodes at a first frequency; deliver a driving signal to the energy delivery device at a second frequency higher than the first frequency; sense an electrical signal from the plurality of electrodes indicative of a bioimpedance of a target tissue; and determine, based on a change in the bioimpedance, whether the target tissue is ablated at a predetermined depth by the energy delivery device.

61. The tissue treatment system of claim 60, wherein the first frequency is 500 kHz or less and the second frequency is 5 MHz or more.

62. A method of confirming tissue ablation, comprising: measuring, by a controller coupled to a tissue treatment catheter, a baseline bioimpedance of a target tissue using a plurality of electrodes on an outer surface of an45 POMD04630SEC_WO01expandable member of the tissue treatment catheter, wherein the expandable member surrounds an energy delivery device of the tissue treatment catheter; delivering energy from the energy delivery device to the target tissue; measuring, by the controller, a post-treatment bioimpedance of the target tissue using the plurality of electrodes; and determining, by the controller, that the target tissue is ablated to a predetermined depth when a difference between the baseline bioimpedance and the post-treatment bioimpedance meets a threshold criteria.46 POMD04630SEC_WO01

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