Fluid controller and power controller of a tissue treatment system

Abstract

A tissue treatment system comprises a fluid supply subsystem having a fluid supply actuator to deliver fluid to a catheter through a supply line and has a supply pressure sensor to detect a fluid pressure of the fluid in the supply line. The tissue treatment system includes a processing device configured to: monitor the fluid pressure and regulate a fluid flow rate based on the monitored fluid pressure during a balloon inflation process, wherein in an initial stage of the inflation process, the balloon is inflated more aggressively than in later stages.

Description

POMD04604SEC_WO01 PATENTFLUID CONTROLLER AND POWER CONTROLLER OF A TISSUE TREATMENTSYSTEMPRIORITY

[0001] This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application Nos. 63 / 696,803, filed September 19, 2024, and 63 / 700,469, filed September 27, 2024, all of which are incorporated herein by reference in their entireties to provide continuity of disclosure.BACKGROUNDFIELD

[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 a fluid controller and a power controller integrated to the apparatuses, systems, and methods for the treatment of tissue, such as nerve tissue.BACKGROUND INFORMATION

[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.

[0005] 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 unfocusedPOMD04604SEC_WO01 PATENT 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.SUMMARY

[0006] The present disclosure is defined in the independent claims. Further embodiments of the present disclosure are defined in the dependent claims.

[0007] A tissue treatment system is provided herein. The tissue treatment system includes a fluid supply subsystem including a fluid supply actuator to deliver fluid to a catheter through a supply line and a supply pressure sensor to detect a fluid pressure of the fluid in the supply line. The tissue treatment system includes a processing device communicatively coupled to the fluid supply subsystem. The processing device is configured to: monitor the fluid pressure and regulate a fluid flow rate based on the monitored fluid pressure during a balloon inflation process, wherein in an initial stage of the inflation process, the balloon is inflated more aggressively than in later stages.

[0008] A method is provided herein. The method includes monitoring, by a processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line. The fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure. The method includes regulating a fluid flow rate based on the monitored fluid pressure during a balloon inflation process, wherein in an initial stage of the inflation process, the balloon is inflated more aggressively than in later stages.

[0009] A method is provided herein. The method includes monitoring, by a processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a return line. The fluid supply subsystem includes a fluid return actuator to remove the fluid from a catheter through the return line and a return pressure sensor to detect the fluid pressure in the return line. The method includes sending, by the processing device in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid return actuator to remove fluid at a first flow rate. The method includes sending, by the processing device in response to the fluid pressure being below the first vacuum valuePOMD04604SEC_WO01 PATENT and above a second vacuum value, a second drive signal to cause the fluid return actuator to remove fluid at a second flow rate. The method includes stopping, by the processing device in response to the fluid pressure being below the second vacuum value, the fluid return actuator.

[0010] A non-transitory computer readable medium is provided herein. The non- transitory computer readable medium stores instructions which, when executed by a processing device of a tissue treatment system, causes the tissue treatment system to monitor, by the processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line. The fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure. The instructions cause the tissue treatment system to regulate a fluid flow rate based on the monitored fluid pressure during a balloon inflation process, wherein in an initial stage of the inflation process, the balloon is inflated more aggressively than in later stages.

[0011] A non-transitory computer readable medium is provided herein. The non- transitory computer readable medium stores instructions which, when executed by a processing device of a tissue treatment system, causes the tissue treatment system to monitor, by the processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a return line. The fluid supply subsystem includes a fluid return actuator to remove the fluid from a catheter through the return line and a return pressure sensor to detect the fluid pressure. The instructions cause the tissue treatment system to send, by the processing device in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid return actuator to remove fluid at a first flow rate. The instructions cause the tissue treatment system to send, by the processing device in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid return actuator to remove fluid at a second flow rate. The instructions cause the tissue treatment system to stop, by the processing device in response to the fluid pressure being below the second vacuum value, the fluid return actuator.

[0012] A tissue treatment system is provided herein. The tissue treatment system includes a fluid supply subsystem including a fluid return actuator to remove fluid from a catheter through a return line and a return pressure sensor to detect a fluid pressure of the fluid in the return line. The tissue treatment system includes a processing device communicatively coupled to the fluid supply subsystem. The processing device is configuredPOMD04604SEC_WO01 PATENT to: monitor the fluid pressure; send, in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid return actuator to remove fluid at a first flow rate; send, in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid return actuator to remove fluid at a second flow rate; and stopping, in response to the fluid pressure being below the second vacuum value, the fluid return actuator.

[0013] A controller of a tissue treatment system is provided herein. The controller includes an excitation source to provide energy to an ultrasound transducer of a catheter. The controller includes a memory storing digital-to-analog (DAC) count models relating DAC count of the excitation source to power output of the ultrasound transducer. The controller includes a processing device communicatively coupled to the excitation source and the memory. The processing device is configured to: send, to the excitation source, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models, determine a difference between an actual power output of the ultrasound transducer and the target power output, and determine, based on the difference, a second DAC count model of the DAC count models, and send, to the excitation source, a second DAC count related to the target power output by the second DAC count model. A method is provided herein. The method includes storing, by a memory of a controller of a tissue treatment system, DAC count models relating DAC count of an excitation source to power output of an ultrasound transducer. The method includes sending, by a processing device of the controller to the excitation source, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models. The method includes determining, by the processing device, a difference between an actual power output of the ultrasound transducer and the target power output. The method includes determining, by the processing device based on the difference, a second DAC count model of the DAC count models. The method includes sending, by the processing device to the excitation source, a second DAC count related to the target power output by the second DAC count model.

[0014] A non-transitory computer readable medium is provided herein. The non- transitory computer readable medium stores instructions which, when executed by a processing device of a controller of a tissue treatment system, cause the tissue treatment system to store, by a memory of the controller, DAC count models relating DAC count of anPOMD04604SEC_WO01 PATENT excitation source to power output of an ultrasound transducer. The instructions, when executed by the processing device, cause the tissue treatment system to send to the excitation source by the processing device, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models. The instructions, when executed by the processing device, cause the tissue treatment system to determine, by the processing device, a difference between an actual power output of the ultrasound transducer and the target power output. The instructions, when executed by the processing device, cause the tissue treatment system to determine, based on the difference, a second DAC count model of the DAC count models. The instructions, when executed by the processing device, cause the tissue treatment system to send, to the excitation source by the processing device, a second DAC count related to the target power output by the second DAC count model.

[0015] The above summary does not include an exhaustive list of all aspects of the present disclosure. It is contemplated that the present disclosure includes all systems and methods that can be practiced from all suitable combinations of the various aspects summarized above, as well as those disclosed in the Detailed Description below and particularly pointed out in the claims filed with the application. Such combinations have particular advantages not specifically recited in the above summary.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings.

[0017] FIG. 1 is a perspective view of a tissue treatment system, in accordance with an embodiment.

[0018] FIG. 2A is a side view of selected components of the tissue treatment system of FIG. 1 , in accordance with an embodiment.

[0019] FIG. 2B is a side view of selected components of the tissue treatment system of FIG. 1 , in accordance with an embodiment.

[0020] FIG. 3 is a perspective view of selected components of the tissue treatment system of FIG. 1 inserted into a body lumen, in accordance with an embodiment.POMD04604SEC_WO01 PATENT

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

[0022] FIG. 5 is a side view of a tissue treatment system having a compliant balloon inflated to a first inflation diameter, in accordance with an embodiment.

[0023] FIG. 6 is a side view of a tissue treatment system having a compliant balloon inflated to a second inflation diameter, in accordance with an embodiment.

[0024] FIG. 7 is a diagram of balloon pressure curves of balloons being inflated according to a pressure limiting approach, in accordance with an embodiment.

[0025] FIG. 8A is a side view of a balloon having wrinkles when inflated to less than its nominal inflation diameter, in accordance with an embodiment.

[0026] FIG. 8B is a perspective view of a balloon having helical folds when inflated to less than its nominal inflation diameter, in accordance with an embodiment.

[0027] FIG. 8C is a perspective view of a balloon having longitudinal folds when inflated to less than its nominal inflation diameter, in accordance with an embodiment.

[0028] FIG. 8D is a cross-sectional view of a balloon having longitudinal folds when inflated to less than its nominal inflation diameter, in accordance with an embodiment.

[0029] FIG. 8E is a perspective view of a balloon having helical folds when inflated to less than its nominal inflation diameter, in accordance with an embodiment.

[0030] FIG. 8F is a cross-sectional view of a balloon having helical folds when inflated to less than its nominal inflation diameter, in accordance with an embodiment.

[0031] FIG. 9 is a diagram of a balloon pressure curve of a compliant balloon being inflated according to a hybrid inflation approach, in accordance with an embodiment.

[0032] FIG. 10 is a schematic of a fluid supply subsystem, in accordance with an embodiment.

[0033] FIG. 11A is a schematic of a controller, in accordance with an embodiment.

[0034] FIG. 1 IB is a schematic of the ultrasound excitation source, introduced in FIG.11 A, in accordance with an embodiment.

[0035] FIG. 12 A is a graph of Acoustic Entry Power versus body lumen size corresponding to an example implementation of single power embodiments for treating target tissue, in accordance with an embodiment.

[0036] FIG. 12B is a graph of Acoustic Entry Power versus body lumen size corresponding to another example implementation of the single power embodiments for treating target tissue, in accordance with an embodiment.POMD04604SEC_WO01 PATENT

[0037] FIG. 13 A is a graph of Acoustic Entry Power versus body lumen size corresponding to an example implementation of two power embodiments for treating target tissue, in accordance with an embodiment.

[0038] FIG. 13B is a graph of Acoustic Entry Power versus body lumen size corresponding to another example implementation of the two power embodiments for treating target tissue.

[0039] FIG. 13C is a graph of Acoustic Entry Power versus body lumen size corresponding to a still further example implementation of the two power embodiments for treating target tissue.

[0040] FIG. 14 is an example graphical user interface (GUI) that allows a user to specify whether a diameter of a body lumen is within a lower subrange of a specified range of diameters or within an upper subrange of the specified range of diameters, which GUI can be used with the two power embodiments.

[0041] FIG. 15 is a high level flow diagram used to summarize a single power method for use with a tissue treatment system having a catheter that includes a distal portion on which is located an ultrasound transducer.

[0042] FIG. 16 is a high level flow diagram used to summarize a two power method for use with a tissue treatment system having a catheter that includes a distal portion on which is located an ultrasound transducer.

[0043] FIG. 17A is a flowchart of a method of inflating a balloon, in accordance with certain embodiments.

[0044] FIG. 17B is a flowchart of a method of inflating a balloon, in accordance with certain embodiments.

[0045]

[0046] FIG. 18 A is a graph of fluid pressure of a tissue treatment system versus time, in accordance with certain embodiments.

[0047] FIG. 18B is a graph of fluid flow of a tissue treatment system versus time, in accordance with certain embodiments.

[0048] FIG. 19 is a graph of balloon pressure of a tissue treatment system versus time, in accordance with certain embodiments.

[0049] FIG. 20 is a flowchart of a method of deflating a balloon, in accordance with certain embodiments.POMD04604SEC_WO01 PATENT

[0050] FIG. 21 A is a graph of fluid pressure of a tissue treatment system versus time, in accordance with certain embodiments.

[0051] FIG. 2 IB is a graph of fluid flow of a tissue treatment system versus time, in accordance with certain embodiments.

[0052] FIG. 22 is a graph of balloon pressure of a tissue treatment system versus time, in accordance with certain embodiments.

[0053] FIG. 23 is a graph of power output of an ultrasound transducer versus time, in accordance with certain embodiments.

[0054] FIG. 24 is a schematic of a power controller of a tissue treatment system, in accordance with certain embodiments.

[0055] FIG. 25 is a flowchart of a method of controlling power output of an ultrasound transducer by a controller of a tissue treatment system, in accordance with certain embodiments.

[0056] FIG. 26 is a graph of DAC count of an excitation source versus power output of a first ultrasound transducer, in accordance with certain embodiments.

[0057] FIG. 27 is a graph of DAC count of an excitation source versus power output of a second ultrasound transducer, in accordance with certain embodiments.

[0058] FIG. 28 is a graph of a first DAC count model relating DAC count of an excitation source to power output of an ultrasound transducer, in accordance with certain embodiments.

[0059] FIG. 29 is a graph of several DAC count models relating DAC count of an excitation source to power output of an ultrasound transducer, in accordance with certain embodiments.

[0060] FIG. 30 is a graph illustrating a difference between an actual power output of an ultrasound transducer and a target power output of the ultrasound transducer, in accordance with certain embodiments.

[0061] FIG. 31 is a graph of steady state power output of an ultrasound transducer controlled using integral control, in accordance with certain embodiments.

[0062] FIG. 32 is a graph of steady state power output of an ultrasound transducer controlled using DAC count models, in accordance with certain embodiments.DETAILED DESCRIPTIONPOMD04604SEC_WO01 PATENT

[0063] Systems that use energy, for example, at least one of unfocused ultrasound and electromagnetic radiation like microwaves or light, to treat tissue, and methods of using the same are provided herein. In certain embodiments, energy may be delivered using a thermal energy emitter, for example, using at least one of acoustic-based tissue treatment transducers, tissue treatment electrodes for RF emission, one or more antennas for microwave emission, or tissue treatment lasers for light emission, apparatuses, systems, or portions thereof, are provided. The systems may be catheter-based. The systems may be delivered intraluminally (e.g., intravascularly) so as to place a thermal energy emitter 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 thermal energy emitter can be activated to deliver thermal energy. For example, unfocused ultrasonic energy may be emitted from a transducer 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.

[0064] In certain embodiments, the energy emitter comprises electrodes, which may be monopolar and embedded in or near a surface of a balloon wall, that emit thermal energy using radio frequencies relying on conduction of the heat from to the inner surface of the vessel wall.

[0065] In certain embodiments, the energy emitter comprises one or more antennas, e.g., an array of antennas, emitting microwave energy radiating from the emitter to form a volumetric field toward the targeted tissue. In certain embodiments, a cooling balloon may be provided to cool the one or more antennas and / or non-targeted tissue lying outside the target tissue zone that may be heated as a consequence of emitting microwave energy from the one or more antennas. Microwave energy may be delivered to target tissue for at least one energy application cycle, e.g., two to three energy application cycles, ranging from 10 seconds to 600 seconds at a frequency ranging from 900 MHz to 2.5 GHz.

[0066] In certain embodiments, the energy emitter comprises one or more laser fibers disposed on a surface of a balloon, which may emit, e.g., 1064 nm Nd: YAG-laser light using energy densities ranging from 4.5 to 30 J / mm2to generate thermal energy. In certain embodiments, the balloon may be perforated and a treatment / working flowrate of 40 mL / min may be used to remove blood cells from the vicinity of the optical fiber distal tip. In certainPOMD04604SEC_WO01 PATENT embodiments, a treatment dosage of 10 W power for 20 s may be used for at least one energy application cycle, e.g., two to three energy application cycles.

[0067] In certain embodiments, unfocused ultrasonic energy generated by a transducer or piezoelectric material, radio frequency (RF) energy transmitted by electrodes, microwave energy generated by the one or more antennas, laser-light emitted by a laser 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.

[0068] Neuromodulating renal nerves may be used to treat various conditions, e.g., pulmonary hypertension, chronic kidney disease (CKD), cardiovascular disease, atrial fibrillation, stroke, 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, non-alcoholic fatty liver disease, digestive disease, pancreatic cancer, other cancers, tumors, pain, polycystic kidney disease, asthma, sepsis, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), post-traumatic stress disorder (PTSD), sleep apnea, anxiety, depression, metabolic disorder, and insulin resistance, etc. It should be appreciated, however, that the balloon catheters suitably may be used to treat other nerves in and / or around a body lumen and other conditions e.g., the nerves in and / or around a renal artery, superior mesenteric artery, inferior mesenteric artery, femoral artery, pelvic artery, portal vein, hepatic artery, common hepatic artery, gastroduodenal artery, splenic artery, gastric artery, celiac trunk, pulmonary artery, pulmonary vein, aorta, vena cava, etc., 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 with pancreatic cancer, by, e.g., neuromodulating nerves that innervate the pancreas. Ultrasound, RF,POMD04604SEC_WO01 PATENT microwave, or laser energy may also be used to ablate nerves of both the pulmonary vein and the renal arteries to treat atrial fibrillation. In still other examples, ultrasound RF, microwave, or laser energy may additionally or alternatively be used to ablate nerves innervating a carotid body in order to treat hypertension and / or chronic kidney disease.

[0069] Existing systems that use unfocused ultrasound energy to treat tissue may be catheter-based and may incorporate balloons surrounding an ultrasound transducer. A fluid can be circulated within the balloon to both inflate the balloon into contact with the tissue, and to cool the ultrasound transducer. The fluid can be delivered to the balloon through a catheter shaft. When the balloon or the catheter shaft are compliant, e.g., stretchable when placed under pressure, achieving a predetermined balloon inflation size can be challenging. More particularly, a compliant balloon or deformable catheter may experience plastic strain when placed under pressure, and the strain may cause overexpansion of the balloon that is not properly sized to the target anatomy. Furthermore, deformation of the catheter shaft, e.g., when placed under a vacuum during balloon deflation, may cause the catheter shaft to collapse and prolong deflation times. Accordingly, particularly in combination with tissue treatment systems having compliant balloons or deformable catheter shafts, although not limited thereto, a fluid control methodology is needed to prevent overexpansion of the balloon during inflation, while minimizing inflation time, and to reduce deflation times during deflation, as well as control a maximum vacuum experienced by the system.

[0070] A person skilled in the art will recognize that a system that minimizes inflation time and / or reduces deflation time, as well as control a maximum vacuum experienced by the system would also provide advantages to a balloon catheter using a noncompliant balloon.

[0071]

[0072] Existing power controllers use proportional-integral (PI) and / or proportional- integral-derivative (PID) control to control power delivery to ultrasound transducers for performing renal denervation. PI and PID control can regulate the denervation process, however, when applying input power to an ultrasound transducer using such control loop mechanisms, the output power of the ultrasound transducer can drift beyond preferred specifications. For example, the power output of the ultrasound transducer, when ramping up to a steady state, may be nonlinear and, given that existing control methodologies are linear (such as PI and / or PID control), the control loop mechanism may cause initial spikes in power output. Furthermore, power output of the ultrasound transducer, when controlled by PI and / or PID control, may oscillate significantly and deviate from a preferred powerPOMD04604SEC_WO01 PATENT accuracy at steady state due to nonlinearity in the power output of the ultrasound transducer. Such spikes and oscillations can be out of specification and may produce rough and unstable power output that can adversely affect tissue. More generally, control of input power that avoids output power excursions can be important in a medical device that treats humans or animals.

[0073] As described below, embodiments can include a tissue treatment system having a controller to control delivery of fluid to a catheter and / or power to an ultrasound transducer of a catheter. The tissue treatment system may be an ultrasound-based tissue treatment system, used to deliver unfocused ultrasonic energy radially outwardly to treat tissue within a target anatomical region, such as the renal nerves within a renal artery. It will be appreciated, however, that the control methodologies may be used to control fluid to alternative catheters and / or control power transmitted to alternative energy emitters used for tissue ablation, such as microwave or laser or electrodes that can directly apply RF power to target tissue. Also, the tissue treatment system may be used in other, non-renal applications, such as to treat sympathetic nerves of the hepatic plexus within a hepatic artery. Thus, reference to the system as being a renal denervation system, or being used in treating, e.g., neuromodulating, renal nerve tissue using ultrasound energy is not limiting.

[0074] 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.

[0075] 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 directionPOMD04604SEC_WO01 PATENT 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 power controller, to a specific configuration described in the various embodiments below.

[0076] In an aspect, a tissue treatment system includes a fluid controller. The fluid controller can include a control methodology that can, within a required time, stabilize a balloon inflation pressure within a predetermined pressure range specified for balloon inflation. For example, the flow rate can be controlled to pump fluid into the balloon until a predetermined pressure is reached, and then the inflation can be slowed or stopped to allow equalization of the balloon pressure to the surrounding vessel. Furthermore, the control methodology can ensure that pressure is equalized through a catheter shaft without causing the catheter shaft to collapse and restrict fluid flow during balloon deflation. For example, the flow rate can be controlled to pump fluid out of the balloon at a rate that does not cause a fluid lumen within the catheter shaft to restrict fluid flow. Accordingly, the control methodology can conditionally control fluid supply and fluid return of the tissue treatment system to optimize balloon inflation and balloon deflation.

[0077] In an aspect, a tissue treatment system includes a power controller. The controller can include a control methodology that is not a typical PI or PID control methodology. More particularly, the controller can implement a control methodology that is suitable for controlling a nonlinear process. The tissue treatment system can incorporate an ultrasound transducer that emits power nonlinearly with respect to DAC count of an excitation source and, thus, the controller can be better suited to control of the denervation process than existing controllers. The controller may implement DAC count models, which may be empirically derived from measured power output of several excitation sources, and the models can relate power output of the ultrasound transducer to DAC count of the excitation source. The DAC models can be stored and referenced by the controller during process control to correct for errors between target and actual power output. For example, the controller can change models by adjusting a coefficient within the model to more closely match the measured behavior of the system. The correction can produce smooth, stable, and controllable power output that affects tissue that a physician intends to treat, without affecting other tissue. Other controller features, such as a low-pass filter used to measure return power, can reduce noise and result in more accurate control. More broadly, the controller can contribute to safe and effective operation of the tissue treatment system.POMD04604SEC_WO01 PATENT

[0078] Referring to FIG. 1 , a perspective view of selected components of a tissue treatment system is shown in accordance with certain embodiments. A tissue treatment system 100 may be a catheter-based system. More particularly, the system 100 can include a catheter 102 that can be delivered intraluminally, e.g., intravascularly, to a target anatomical region of a subject. When so placed, a transducer of the system (FIG. 2A) can be positioned within a target anatomy, e.g., within a body lumen such as a blood vessel. As described below, the transducer can be an ultrasound transducer that may be disposed within a balloon 108. The transducer can be activated to deliver unfocused ultrasonic energy radially outwardly so as to suitably heat, and thus treat, tissue within the target anatomical region. The transducer can be activated at a frequency, time, and energy level suitable for treating the targeted tissue.

[0079] The tissue treatment system 100 may include the catheter 102, a controller 104, and a connection cable 106. The tissue treatment system 100 further includes a balloon 108, a reservoir 110, optionally a cartridge 112, and a control mechanism, such as a handheld remote control. In certain embodiments, the tissue treatment system 100 includes a tubing kit instead of a cartridge 112. In certain embodiments, the controller 104 is connected to the catheter 102 through the cartridge 112 or tubing kit and the connection cable 106. In certain embodiments, the controller 104 interfaces with the cartridge 112 to provide cooling fluid to the catheter 102 for inflating and deflating the balloon 108. The controller 104 can also be referred to as the control unit 104.

[0080] In certain embodiments, a catheter 102 can include a compliant balloon 108 configured to accommodate a range of target vessel sizes, as described below. In other embodiments, a catheter 102 can include a noncompliant balloon 108 configured to accommodate a more narrow range of target vessel sizes. A compliant balloon 108 can accommodate larger differences, e.g., 2 mm or greater, in vessel lumen diameter along the artery length and between left and right renal arteries. For example, the compliant balloon 108 may be configured to treat a blood vessel having a vessel lumen diameter between 3 to 8.5 mm in diameter. In another example, the compliant balloon 108 may be configured to treat a blood vessel having a vessel lumen diameter between 3 to 9 mm in diameter. Thus, the compliant balloon 108 can mitigate the need to use several different balloon catheters 102 per procedure. Accordingly, a compliant balloon 108 can reduce procedure times and complexity.POMD04604SEC_WO01 PATENT

[0081] Referring to FIG. 2A, a side view of selected components of the tissue treatment system of FIG. 1 is shown in accordance with certain embodiments. The tissue treatment catheter 102 can include a distal region 202 and a proximal region 204. The catheter 102 may have a length that depends on a treatment application. For example, in certain embodiments suitable for, e.g., renal denervation through a femoral access delivery method, the catheter 102 can have a working length (measured from a distal tip of the catheter 102 to a proximal hub 240 of the catheter 102) of 80 to 90 cm, e.g., 85 cm, in the femoral access delivery method. In embodiments suitable for, e.g., renal denervation through a radial access delivery method, the catheter 102 can have a working length of a comparatively longer length. More particularly, the working length can be 150 to 160 cm, e.g., 155 cm. Furthermore, an overall length of the catheter 102 for such application, including a length of cabling extending to an electrical coupling 206, can be longer. More particularly, the cabling can have a length of about 305 cm from the proximal hub 240 to the electrical coupling 206.

[0082] The catheter 102 can have a profile that is suitable to accessing a renal artery through the femoral and radial access locations. For example, the catheter 102 may be 4 to 6 French in diameter, e.g., 5 French. The profile is facilitated in part by a catheter shaft 212 having an outer diameter in a range of 0.050 to 0.060 inch, e.g., 0.057 inch.

[0083] The distal region 202 of the tissue treatment system 100 may be a portion of the device that is advanced into a target anatomy, e.g., a target vessel having a vessel wall, to treat the target vessel. The distal region 202 can include the balloon 108 mounted on a catheter shaft 212. The balloon 108 can be a compliant balloon having the characteristics described in detail below or a noncompliant balloon. For example, a complaint balloon 108 can have a cylindricity that supports and centers a transducer 214 within a range of vessel diameters, e.g., within arteries, e.g., renal and / or hepatic arteries, ranging from 3 to 8.5 mm, and thus, contributes to uniform energy delivery.

[0084] The catheter shaft 212 can be an elongated tubular structure that extends longitudinally from a proximal end to a distal end. The balloon 108 can be mounted and supported on the catheter shaft 212 at the distal end. Furthermore, the ultrasound transducer 214 can be mounted on the catheter shaft 212 and contained within the balloon 108. Accordingly, the catheter shaft 212 can facilitate delivery of a cooling fluid to the balloon 108 and delivery of electrical energy to the transducer 214.POMD04604SEC_WO01 PATENT

[0085] The catheter shaft 212 can include one or more lumens (FIG. 4) that may be used as fluid conduits, electrical cabling passageways, guidewire lumens, and / or the like. In certain embodiments, the catheter shaft 212 can include a guidewire lumen 213 that is shaped, sized and otherwise configured to receive a guidewire. In certain embodiments, the guide wire lumen 213 is an over-the-wire type guidewire lumen, extending from a distal tip of the catheter 102 through an entire length of the catheter shaft 212 to an exit port 250 in the proximal hub 240 of the catheter 102. As described below, the lumen(s) of the catheter shaft 212 may also communicate inflation / cooling fluid from the proximal region 204 to the balloon 108 during balloon expansion.

[0086] In certain embodiments, a transducer 214 is mounted on the catheter shaft 212 at the distal region 202, within an interior of the balloon 108. The transducer 214 can be an ultrasound transducer 214 used to emit energy toward the vessel wall. For example, the transducer 214 can emit ultrasound energy circumferentially, e.g., 360 degrees, around the vessel wall. In certain embodiments, electric cabling 216 extends from the proximal region 204 to the distal region 202, and is connected to the transducer 214 to generate energy for emission to target tissue.

[0087] The ultrasound transducer 214 may include first and second electrodes that are arranged on either side of a cylindrical piezoelectric material, such as lead zirconate titanate (PZT). To energize the transducer 214, a voltage is applied across the first and the second electrodes at frequencies selected to cause the piezoelectric material to resonate, thereby generating vibration energy that is emitted radially outward from the transducer 214. The transducer 214 is designed to provide a uniform and predictable emission profile, to inhibit damage to surrounding non-target tissue. In addition, a cooling fluid is circulated through the balloon 108, both prior to, during, and after activation of the transducer 214, so as to reduce heating of an inner lining of the body lumen and to cool the transducer 214. In this manner, the peak temperatures achieved by tissue within the cooling zone remain lower than for tissue located outside the cooling zone.

[0088] The proximal region 204 may include one or more connectors or couplings. The connectors or couplings can be electrically connected to the transducer 214 via the electric cabling 216. For example, the proximal region 204 may include one or more electrical coupling 206 that connects to a proximal end of the electric cabling 216. A distal end of the electric cabling 216 can be connected to the transducer 214.POMD04604SEC_WO01 PATENT

[0089] The catheter 102 may be coupled to the controller 104 by connecting the electrical coupling 206 to the connection cable 106. The connection cable 106 may be removably connected to the controller 104 and / or the catheter 102 via a port on the controller 104 and / or the catheter 102. Accordingly, the controller 104 can be used with several catheters 102 during a procedure by disconnecting the coupling of a first catheter, exchanging the first catheter with a second catheter, and connecting a coupling of the second catheter to the controller 104. In certain embodiments, e.g., where only one catheter needs to be used during a procedure, the connection cable 106 may be permanently connected to the controller 104.

[0090] In certain embodiments, the proximal region 204 of the catheter 102 may further include one or more fluidic ports. For example, the proximal hub 240 can include a fluidic inlet port 208 and a fluidic outlet port 210, via which an expandable member, e.g., the balloon 108, may be fluidly coupled to the reservoir 110 (FIG. 1). The reservoir 110 can therefore supply cooling fluid to the balloon 108 through the fluidic ports. The reservoir 110 optionally may be included with the controller 104, e.g., attached to the outer housing of the controller 104 as shown in FIG. 1. Alternatively, the reservoir 110 may be provided separately.

[0091] Referring to FIG. 2B, a side view of selected components of the tissue treatment system of FIG. 1 is shown in accordance with certain embodiments. In certain embodiments, the catheter 102 can have a rapid-exchange type guide wire lumen 213. More particularly, the guidewire lumen 213 can extend from the distal tip of the catheter 102 through a partial length of the catheter shaft 212 to an exit port 250 in the distal portion 202 of the catheter 102. For example, a distance from the distal tip to the rapid exchange port 250 may be in a range of 20 to 30 cm, e.g., 23 cm. The proximal hub 240 illustrated in FIG. 2B may differ from the proximal hub 240 illustrated in FIG. 2A, given that the exit port 250 may be moved from the proximal portion 204 to the distal portion 202. Other components of rapid exchange version of the catheter 102 may be similar to those of the over-the-wire version of the catheter 102, and thus, the descriptions of the components illustrated in FIG. 2 A can apply to similarly numbered components illustrated in FIG. 2B.

[0092] Referring to FIG. 3, a perspective view of additional selected components of the tissue treatment system of FIG. 1 inserted into a body lumen is shown in accordance with certain embodiments. The tissue treatment system 100 can be inserted into a body lumen of a subject. For example, a distal region 202 of the catheter 102 of the tissue treatment systemPOMD04604SEC_WO01 PATENT100 can be advanced into a target vessel 302, e.g., a blood vessel such as a renal artery. The target vessel 302 can have a plurality of nerves 304 in an outer layer, e.g., an adventitia layer, of the target vessel 302. In certain embodiments, the tissue treatment system 100 includes a guide wire support tip 308 having a lumen that connects to the guidewire lumen 213 of the catheter shaft 212. The support tip 308 can receive the guidewire 310 to allow the device to be tracked over a guide wire 310 to the target anatomy.

[0093] When the distal region 202 is disposed in the vessel lumen of the target vessel 302, the transducer 214 and the balloon 108 (or another suitable expandable member) are positioned radially inward from the plurality of nerves 304. The transducer 214 may be disposed partially or completely within the interior of the balloon 108. The balloon 108 can be filled with an inflation fluid 306, e.g., a cooling fluid, to expand the balloon 108. When the balloon 108 is inflated with the inflation fluid 306, the balloon 108 can contact an interior surface, e.g., an intima, of the target vessel. The expanded balloon 108 may therefore have an inflated diameter equal to a lumen diameter 320 of the target vessel 302, and appose the target vessel 302 and center the transducer 214 within the target vessel 302.

[0094] In certain embodiments, the transducer 214 may be used to output an acoustic signal when the balloon 108 fully occludes the target lumen. The balloon 108 may center the transducer 214 within the target lumen. In certain embodiments, e.g., suitable for renal denervation, the balloon 108 may be a compliant balloon 108, as described below, which may be inflated in the patient during a procedure at a working pressure of about 10 psi, e.g., 9 to 10 psi, using the inflation fluid 306. In certain embodiments, e.g., suitable for renal denervation, the balloon 108 may be a compliant balloon 108, as described below, which may be inflated in the patient during a procedure at a working pressure of about or less than 30 psi using the inflation fluid 306. In certain embodiments, the balloon 108 nay be a compliant or noncompliant balloon sized for insertion in the target lumen and, in the case of insertion of the renal artery, for example, the balloon 108 may be selected to have expansion sizes including outer diameters of one or more of 3.5 mm, 4.2 mm, 5 mm, 6 mm, 7 mm, 8 mm, or 9 mm. The balloon 108 may have a burst strength of greater than 33 psi, e.g., greater than 45 psi.

[0095] In some embodiments, when inflated by being filled with the inflation fluid 306 under the control of the controller 104 within the target vessel 302, a balloon wall of the balloon 108 may be parallel with an outer surface of the transducer 214. Optionally, the balloon 108 may be inflated sufficiently as to be in apposition with the target vessel. ForPOMD04604SEC_WO01 PATENT example, when inflated, the balloon 108 may at least partially contact, and thus be in apposition with, the inner wall of the target vessel. In other embodiments, the balloon 108 is configured not to contact the target vessel when expanded. The balloon 108 may be maintained at a specified size by pushing fluid into, e.g., via the inlet port 208, and pulling fluid out of, e.g., via the outlet port 210, the balloon 108 at a specified flow rate. More particularly, the inflation fluid 306 can circulate within the balloon 108 to expand the balloon 108.

[0096] Referring to FIG. 4, a longitudinal cross-sectional view of the distal region of a tissue treatment system is shown in accordance with certain embodiments. In certain embodiments, the catheter shaft 212 may be about 1.8 mm in diameter. As described above, the catheter shaft 212 includes one or more thromboembolism lumens that may be used as fluid conduits, passageways for electrical cabling or the guidewire 310, etc. For example, the catheter shaft 212 may include the guide wire lumen 213 that is shaped, sized and otherwise configured to receive the guidewire 310. The catheter shaft 212 may include a cable lumen 401 (extending through a same shaft as the guidewire lumen 213) for receiving the electrical cabling, and / or fluid lumens for transferring the inflation / cooling fluid, e.g., water, sterile water, saline, 5% dextrose (D5W), other liquids or gases, etc., from and to a fluid source, e.g., the reservoir 110, at the proximal region 204 of the catheter 102 external to the patient. The catheter shaft 212 can include one or more fluid channels 420 to move fluid into or out of a balloon 108. For example, the fluid channel(s) can include an inlet channel 403 to deliver the inflation fluid 306 from the inlet port 208 to the balloon 108 under control of the controller 104. Similarly, the fluid channel(s) can include an outlet channel 405 to remove fluid from the balloon 108 to the outlet port 210. Accordingly, the inlet channel 403 and the outlet channel 405 are in fluid communication with the balloon 108 to circulate fluid through the balloon 108 at a flow rate selected to inflate the balloon 108. The flowrate also controls heat transfer between the balloon 108 and the vessel wall 303 to reduce a likelihood of overheating tissue during treatment. For example, the flowrate can provide for active cooling of about the first millimeter of tissue to preserve the integrity of, e.g., the renal arterial wall.

[0097] In certain embodiments suitable for, e.g., renal denervation, the guidewire 310 has a diameter of about 0.36 mm and a length of from about 180 cm to about 300 cm, and is delivered using a 7 French guide catheter, having a minimum inner diameter of 2.06 mm and a length less than about 80 cm. In certain embodiments, a 6 French guide catheter is used to deliver the guide wire 310. In certain embodiments, such as those used with radial arteryPOMD04604SEC_WO01 PATENT access, a 5 French guide catheter is used to deliver the guidewire 310. In certain embodiments, the guide catheter has a length of about 55 cm. In certain embodiments, the guide catheter has a length of about 85 cm and a hemostatic valve is attached to the hub of the guide catheter for continuous irrigation of the guide to decrease the risk of thromboembolism. In certain embodiments, the guide wire lumen 213 is located in the center of the catheter shaft 212 in order to center the transducer 214.

[0098] The ultrasound transducer 214 may include a cylindrical tube 402 made of a piezoelectric material, e.g., lead zirconate titanate (PZT), etc., with inner and outer electrodes 404, 406 along the inner and outer surfaces of cylindrical tube 402, respectively. In certain embodiments suitable for, e.g., renal denervation, the piezoelectric material comprises PZT-8 (Navy III). Raw PZT transducers 214 may be plated with layers of copper, nickel, and gold to create electrodes on the inner and outer surfaces of the cylinder. Application of alternating current across inner and outer electrodes 406 causes the piezoelectric material to vibrate transverse to the longitudinal direction of the cylindrical tube 402 and radially emit ultrasonic waves.

[0099] In addition, the transducer 214 is supported via backing member or post 408. In certain embodiments, backing member 408 comprises stainless steel coated with nickel and gold, wherein nickel is used as a bonding material between the stainless steel and gold plating. In certain embodiments suitable for, e.g., renal denervation, the outer diameter of the transducer 214 is about 1.5 mm, the inner diameter is about 1 mm, and the transducer 214 has a length, for example, in a range of 3 to 9 mm, such as 6 mm. The backing member 408 may extend from the distal end of the catheter shaft 212 to the support tip 308. For example, the distal end of the backing member 408 may be positioned within an adjacent opening in the support tip 308, and the proximal end of the backing member 408 may be moveably coupled to the distal end of the catheter shaft 212 via the electrical cabling. In other embodiments, there is a gap 410 between the distal end of the catheter shaft 212 and the backing member 408 supporting the transducer 214, and / or a gap between the backing member 408 and the support tip 308.

[0100] In order to permit liquid cooling along both the inner and outer electrodes 406, the backing member 408 may include one or more stand-off assemblies 412. The stand-off assemblies may define one or more annular openings 414 through which cooling fluid may enter the space between the backing member 408 and the inner electrode 404. The backing member 408 may serve as a fluid barrier between the inflation / cooling fluid circulated withinPOMD04604SEC_WO01 PATENT the balloon 108 and the lumen of the backing member 408 that receives the guidewire 310. The stand-off assemblies of the backing member 408 may be positioned along each end of the ultrasound transducer 214 (separated by a main post body 416) and couple the cylindrical tube 402 of the ultrasound transducer 214 to the backing member 408. The stand-off assembly 412 may have a plurality of lugs, ribs, or attachment points that engage the inner electrode 404 of the transducer 214. In certain embodiments, the attachment points are soldered to the inner electrode 404 of the transducer 214. The number, dimensions, and placement of the ribs may vary, as desired or required. For example, a total of three ribs are equally spaced apart from one another at an angle of 120 degrees, defining the annular openings 414 through which fluid and blood may enter the interior space of the cylindrical tube 402 between the inner electrode 404 disposed along the inner surface of the cylindrical tube 402 and the backing member 408. In certain embodiments, the maximum outer diameter of the stand-off assemblies is about 1 mm, the outer diameter of the main post body 416 is about 0.76 mm, and the inner diameter of the backing member 408 is about 0.56 mm.

[0101] The stand-off assemblies may be electrically conductive, so as to electrically couple the inner electrode 404 of the ultrasound transducer 214 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 104 is activated, current may be delivered from the electrical cabling to the inner electrode 404 of the ultrasound transducer 214 via the backing member 408 and the stand-off assemblies, which advantageously eliminates the need to couple the electrical cabling directly to the inner electrode 404 of the transducer 214.

[0102] In certain embodiments, the backing member 408 may have an isolation tube (not shown) disposed along its interior surface so as to prevent or reduce the likelihood of electrical conduction between the guide wire 310 and the backing member 408. The isolation tube may be formed of a non-conductive material, e.g., a polymer such as polyimide. The isolation tube may extend from the distal end of the catheter shaft 212 through the lumen of the backing member 408 within the transducer 214 to the support tip 308. The transducer 214 can be mounted on the isolation tube and / or the electrical cabling. In this manner, the transducer 214 can be distally offset from the distal end of catheter shaft 212 by the gap 410.

[0103] The catheter 102 may also include a bore 418 extending from the distal end of the catheter shaft 212 proximally within the catheter 102. The bore 418 can be sized and shaped to receive at least a portion of the backing member 408, the electrically insulating isolation tube, and / or the ultrasound transducer 214. Accordingly, during delivery of thePOMD04604SEC_WO01 PATENT catheter 102 to the anatomical region being treated, the backing member 408, the isolation tube, and / or the ultrasound transducer 214 may be retracted within the bore 418 of the catheter 102, e.g., by retracting the electrical cabling, thereby providing sufficient stiffness to the catheter 102 such that the catheter 102 may be delivered in a safe manner.

[0104] Referring to FIG. 5, a side view of a tissue treatment system having a compliant balloon inflated to a first inflation diameter is shown in accordance with certain embodiments. In certain embodiments, the balloon 108 is compliant and configured to be deployed in a wide range of lumen, blood vessel, or artery sizes. For example, the balloon 108 may be capable of adapting to arteries with an inner diameter in the range of 3 mm to 8.5 mm. Accordingly, using the compliant balloon 108 permits only one catheter 102 to be used during a procedure, advantageously decreasing operating time, e.g., from about 1 hour to about 15 minutes for, e.g., a renal denervation procedure. In certain embodiments, the use of a compliant balloon decreases the complexity, and thereby the rate of complications, of the procedure.

[0105] In certain embodiments, the tissue treatment system 100 is configured to measure the lumen, blood vessel, or artery sizes, and since the balloon 108 is configured to accommodate a wide range of body lumen sizes, e.g., from about 3 mm to about 9 mm renal or accessory arteries, the controller 104 can be programmed to automatically inflate the balloon 108 to the appropriate diameter. Such automation advantageously provides improvements to the complexity of the procedure and mitigates a risk of user error. In certain embodiments, the tissue treatment system 100 having a compliant balloon 108 does not require the user to choose a balloon size and / or switch out catheters to provide multiple sized balloons during a single procedure.

[0106] The compliant balloon 108 can include a balloon wall 502, which at any longitudinal location, may have an annular cross-section. More particularly, the balloon wall 502 can have an outer surface that expands into contact with the target tissue, and an inner surface that defines an interior 504 of the balloon 108. As described above, the transducer 214 can be mounted on the catheter shaft 212, either directly or indirectly (e.g., via the electrical cabling).

[0107] The transducer 214 can be positioned within the interior 504 of the balloon 108. More particularly, the balloon 108 can have a balloon body 506, and the balloon body can radially surround the transducer 214. For example, the balloon body 506 can be a cylindrical portion of the balloon wall 502 that extends radially around the transducer 214POMD04604SEC_WO01 PATENT relative to a longitudinal axis of the catheter shaft 212. The balloon body 506 can extend longitudinally between a plurality of corners 508. For example, a distal corner 508A can define a distal extent of the balloon body 506, and a proximal corner 508B can define a proximal extent of the balloon body 506. In certain embodiments, a distance between the corners 508, which defines a length of the balloon body 506, can be equal to or greater than a length of the transducer 214. More particularly, the balloon’s body length may be, at a minimum, the length of the transducer 214. Accordingly, the transducer 214 can be positioned such that a proximal end of the transducer 214 is distal to the proximal corner 508B of the balloon 108, and a distal end of the transducer 214 is proximal to the distal corner 508A of the balloon 108. The corners 508 can transition the balloon body 506 into a plurality of shoulders 510. Furthermore, in addition to transitioning the balloon 108 sections, the shape of the corners 508 can have a primary impact on the ability of the balloon 108 to center the transducer 214 within the target vessel 302.

[0108] In certain embodiments, the plurality of shoulders 510 include a distal shoulder 510A (distal to the balloon body 506) that connects the balloon body 506 to a distal mounting section 512A of the balloon wall 502. Similarly, a proximal shoulder 510B (proximal to the balloon body 506) can connect the balloon body 506 to a proximal mounting section 514B of the balloon wall 502. Accordingly, the shoulders 510 transition the portions of the balloon wall 502 that connect the balloon 108 to the catheter shaft 212 with the portion of the balloon wall 502 that interacts with the target tissue during expansion.

[0109] The transducer 214 can be mounted on the isolation tube and / or the backing member 408. In this case the proximal mounting section 514B can be mounted on the catheter shaft 212 proximal to the transducer, but the distal mounting section 512A can be mounted on the transducer, backing member 408 or support tip 308. The mounting sections may be connected to the catheter shaft 212 via thermal, adhesive, or mechanical joints that hermetically seal the balloon 108 to the catheter shaft 212. Accordingly, the interior 504 of the balloon 108, which is between the mounting points, can surround the transducer 214 and provide a space for the inflation / cooling fluid to circulate around the transducer 214 during treatment, as well as prior to and / or after treatment.

[0110] It will be appreciated that, as opposed to compliant balloons 108 that primarily function to occlude a target anatomy, the balloon 108 of the tissue treatment system 100 functions to center the transducer 214 within the target vessel 302. The flexibility of the balloon 108 required to achieve the inflation methodologies described below, however, mayPOMD04604SEC_WO01 PATENT lead to the transducer 214 becoming eccentric with the vessel lumen if particular features are not implemented in the balloon 108. More particularly, in certain embodiments, a shape and material of the balloon 108 can be provided as described below to provide a compliant balloon 108 that is also supportive enough to center the transducer 214 within the target vessel 302 during use.

[0111] In certain embodiments, the shape of the balloon 108 can contribute to optimally centering the transducer 214 within the target vessel 302. In certain embodiments, the balloon body 506 and the plurality of shoulders 510 meet at round corners 508. The corners 508 may be considered round because, rather than the transition between the shoulder 510 and the balloon body 506 being sharp or angular, the transition has a smooth, arcuate profile. The profile can be described as having a full radius, as opposed to a discrete change in radius that would be apparent, for example, in medical balloons typically used for angioplasty procedures. It has been shown that, as compared to balloon shapes having sharp corners, the round corners 508 of the balloon 108 provide that, when the balloon 108 is inflated within the target vessel 302, the catheter shaft 212 (and the transducer 214 mounted on the catheter shaft 212) remains centered in the target vessel 302.

[0112] The material of the balloon 108 can contribute to optimally centering the transducer 214 within the target vessel 302. In certain embodiments, e.g., suitable for renal denervation, the balloon 108 may comprise nylon, polyether block amide (PEBAX®), or other suitable polymers. In certain embodiments, the balloon wall 502 is formed from an elastomeric material. For example, the elastomeric material can include a urethane material, such as a thermoplastic polyurethane (TPU). The TPU can be a polyether-based TPU, such as Pellethane®. Alternatively, the balloon wall 502 may be formed from another medical grade polyether-based TPU, such as Isothane®.

[0113] Isothane® is a urethane material having a material specification that is tightly controlled. As compared to other types of urethane, Isothane® may be particularly useful in that variation in material properties between lots of material are low. More particularly, from lot to lot, Isothane® may have fewer gels and more consistent block chains as compared to other materials. Accordingly, in certain embodiments, the raw material used to form the balloon 108 is Isothane®.

[0114] A hardness of the balloon material can contribute to the compliance of the balloon 108, e.g., an ability of the balloon to expand and conform to different vessel lumen diameters. The hardness can also contribute to the ability of the balloon 108 to supportivelyPOMD04604SEC_WO01 PATENT center the transducer 214. Accordingly, the material used to form the balloon wall 502 may have a Shore durometer between about 95A and about 55D. More particularly, the balloon wall material can have a Shore D durometer in a range of 50 to 60. For example, the balloon 108 may be formed from Pellethane® having a Shore D durometer of 55, or Isothane® having a shore durometer of 5095A, 7195A, or 5055D. In a particular embodiment, it has been shown that the balloon wall 502 formed from Isothane® having a Shore D durometer of 55 can provide excellent results in balancing the performance goals of compliant expansion with supportive strength.

[0115] Whereas non-compliant balloon inflation is limited by the balloon itself, i.e., the balloon diameter is fixed when inflated at different pressures within the expected operating range, and therefore can accommodate a limited range of vessel sizes, compliant balloon expansion can employ multiple methods of inflation that allow the compliant balloon to accommodate a larger range of vessel sizes, e.g., blood vessels that vary 2 mm or more in diameter. The compliant balloon 108 of the tissue treatment system 100 described above can be deployed in the target vessel 302 using any of several inflation methodologies. Such methodologies can be termed a “pressure limiting approach,” an “arterial limiting approach,” and a “hybrid approach.”

[0116] The pressure limiting approach involves using specific inflation pressures to attain specific balloon diameters to gain apposition to various vessel sizes. The arterial limiting approach involves using a fixed inflation pressure that is used regardless of arterial diameter. The hybrid approach is a combination of the arterial limiting and pressure limiting approaches. The hybrid approach involves using a fixed inflation pressure to gain apposition to smaller arterial diameters, but using alternate (higher) inflation pressures to gain apposition to larger arterial diameters. The strength of the artery effectively determines the size of the balloon 108 at low pressures, and at higher pressures the balloon pressure determines the size of the balloon 108. These inflation paradigms are described in further detail below.

[0117] Still referring to FIG. 5, a compliant balloon 108 is shown in a first state and, more particularly, at a first inflation diameter. The inflation diameter can be an outer dimension of the balloon body 506. In certain embodiments, the balloon wall 502 has a shape and stiffness (as described herein) such that, when the compliant balloon 108 is inflated to a first working inflation pressure of 10 psi, the balloon body 506 of the balloon wall 502 has a cylindrical profile and a first inflation diameter of 3.5 mm to 6 mm. The working inflation pressure, i.e., the inflation pressure at which treatment is provided and / or the innerPOMD04604SEC_WO01 PATENT blood vessel wall is actively cooled, can correspond to a flowrate of fluid circulated through the interior 504 of the balloon 108 between the inlet channel 403 and the outlet channel 405. For example, the fluid may be circulated at a flowrate of 15 to 35 mL / min (e.g., 25 to 35 mL / min) to inflate the balloon 108 to the working inflation pressure of 10 psi, which results in the first inflation diameter of 3 to 6 mm (e.g., 3.5 to 6 mm). The balloon body 506 of the balloon 108 can have the first inflation diameter of 3.5 mm at a first working inflation pressure of 10 psi and a flowrate of 30 mL / min. It is noted that the term flowrate can also be equivalently expressed as two words, i.e., flow rate.

[0118] In certain embodiments used for the pressure limiting approach, a single balloon 108 can have an inflation diameter that is directly related to the pressure in the balloon 108. More particularly, the outer diameter of the balloon 108 is directly related to the pressure in the balloon 108. According to this embodiment, the higher the pressure, the bigger the balloon 108. It is contemplated that the balloon 108 may have an expansion range of 3.5 to 9 mm. More particularly, the balloon 108 may have a nominal size of 3.5 mm when inflated to the state shown in FIG. 5, however, as the inflation pressure is increased, the inflation diameter may also increase.

[0119] Referring to FIG. 6, a side view of a tissue treatment system having a compliant balloon inflated to a second inflation diameter is shown in accordance with certain embodiments. When the balloon 108 is inflated to a second inflation diameter, e.g., 8 mm, the balloon wall 502 can have the same sections described above. More particularly, the compliant balloon 108 can include the mounting sections 512A, 514B, shoulders 510A,B, and balloon body 506. The corners 508 A, B, which transition the balloon body 506 into the shoulders 510A,B, can be rounded. In certain embodiments, the arcuate corners 508A,B can have a same radius as the balloon body 506 and the shoulders 510A such that the balloon wall 502 has a single, arcuate profile of a same radius between the distal mounting section 512A and the proximal mounting section 514B. As in FIG. 5, the balloon body 506 can be longer than, and surround, the transducer 214 mounted on the catheter shaft 212. Although the shoulders 510A,B may be rounded, as shown, the balloon 108 may have angular shoulders instead.

[0120] In certain embodiments, the balloon wall 502 has a shape and stiffness (as described herein) such that, when the compliant balloon 108 is inflated to a second inflation pressure of 30 psi, the balloon body 506 of the balloon wall 502 has a cylindrical profile and a second inflation diameter of 8 mm to 9 mm. The working inflation pressure can correspondPOMD04604SEC_WO01 PATENT to a flowrate of fluid circulated through the interior 504 of the compliant balloon 108 between the inlet channel 403 and the outlet channel 405. For example, the fluid may be circulated at a working flowrate, i.e., the flow rate during treatment and / or active cooling of the inner vessel wall of 35 to 50 mL / min (e.g., 40 to 45 mL / min) to maintain the balloon 108 to the working inflation pressure of 30 psi, which results in the first inflation diameter of 8 to 9 mm. For example, the balloon body 506 of the balloon 108 can have the second inflation diameter of 8 mm at a second working inflation pressure of 30 psi and a working flowrate of 40 to 45 mL / min.

[0121] Referring to FIG. 7, a diagram of balloon pressure curves of balloons being inflated according to a pressure limiting approach is shown in accordance with certain embodiments. In the pressure limiting approach, the compliant balloon 108 can have a pressure curve that approximates an ideal inflation curve 702. The ideal inflation curve 702 can extend linearly from the first inflation diameter of 3.5 mm at the first working inflation pressure of 10 psi to a second inflation diameter of 8 mm at a second working inflation pressure of 30 psi. The balloon 108 can therefore accommodate a 3.5 to 8 mm vessel lumen diameter of a same vessel or several vessels. More particularly, an inflation diameter 704 of the balloon 108 corresponds to a working inflation pressure 706 of the balloon 108.

[0122] The balloon 108 can be inflated and / or actively cool a blood vessel wall by circulating the inflation fluid 306 within the balloon 108. As described in further detail herein, during inflation, irrigation motor speed is conditionally controlled in order to stabilize the balloon pressure during an inflated state. Then, during treatment and / or active cooling of the vessel wall (before, during, and / or after treatment) a working inflation pressure can be proportional to the working flowrate. Accordingly, the inflation fluid 306 can be circulated within the balloon 108 based on a lumen diameter 320 of the target vessel 302 during treatment and / or active cooling of the inner vessel wall (before, during, and / or after treatment). For example, the working flowrate associated with the second working inflation pressure (and the second inflation diameter) may be greater than the working flowrate associated with the first working inflation pressure (and the first inflation diameter). By way of example, the inflation fluid 306 may be circulated through the balloon 108 at a working flowrate between 25 and 45 mL / min at the inflation diameters 704 along the ideal inflation curve 702 during treatment and / or active cooling of the vessel wall (before, during, and / or after treatment). In certain embodiments, when the inflation fluid 306 is sterile water, the working flowrate may be 30 mL / min to maintain the inflation pressure of 10 psi associatedPOMD04604SEC_WO01 PATENT with the inflation diameter of 3.5 mm during treatment and / or active cooling of the vessel wall (before, during, and / or after treatment). When the inflation fluid 306 is sterile water, the working flowrate may be 40-45 mL / min at the working inflation pressure of 30 psi associated with the inflation diameter of 8 mm. In another embodiment, when the inflation fluid 306 is D5W, the working flowrate may be 27 mL / min to maintain the working inflation pressure of 10 psi associated with the inflation diameter of 3.5 mm. When the inflation fluid 306 is D5W, the working flowrate may be 40 mL / min to maintain the working inflation pressure of 30 psi associated with the inflation diameter of 8 mm. Accordingly, the pressure limiting approach can utilize working flowrates of at least 30 mL / min to maintain working inflation pressures of 10-30 psi. It has been shown that a working flowrate of 11 mL / min or more circulates fluid sufficiently to adequately cool tissue during renal denervation. Using a compliant balloon, it has been demonstrated that a working flowrate of 20 mL / min or more circulates fluid sufficiently to adequately cool tissue during renal denervation using femoral access and a working flowrate of 11 mL / min or more circulates fluid sufficiently to adequately cool tissue during renal denervation using radial access.

[0123] In certain embodiments, the balloon 108 approximates the ideal inflation curve 702 over several inflation cycles. For example, the balloon 108 can be inflated to the first working inflation diameter (or the second working inflation diameter) a first time 708 when the tissue treatment system 100 is introduced into a renal artery. The balloon 108 may be inflated one or more additional times, e.g., a fifth time 710, to treat different regions along a length of the renal artery. It has been shown that, using the materials described above, the inflation curves for the balloon 108 at each inflation cycle approximate each other and the ideal pressure curve. For example, when the balloon 108 is formed from Isothane® 55D, the inflation diameter when the balloon 108 is inflated the first time 708 is within 10% of the inflation diameter when the balloon 108 is inflated the fifth time. By contrast, balloons formed from other materials not contemplated above may exhibit less consistent inflation curves over several cycles. For example, balloons formed from other materials not contemplated above may exhibit inflation diameters 704 at an Nth time 712 that are more than 10% different than inflation diameters 704 at a first time 708. Accordingly, the balloon 108 described herein provides good inflation consistency that permits a single device to be inflated several times to treat a same or different vessels during a single procedure.

[0124] Referring to FIG. 8 A, shown therein is a side view of a balloon 108 that includes wrinkles 800 when the balloon 108 is inflated to less than its nominal inflationPOMD04604SEC_WO01 PATENT diameter, which may occur while the balloon is inserted into a target body lumen having a lumen diameter that is less than the nominal inflation diameter. For example, the balloon 108 may have a nominal inflation diameter of 8 mm (or 5 mm, or 6 mm, or 6.5 mm, etc.), yet be inserted into a portion (also known as segment) of a body lumen (e.g., a renal artery) having a lumen diameter of 3.5 mm. Therefore, when the balloon 108 is placed in the target body lumen having a smaller lumen diameter than the nominal inflation diameter of the balloon (also known as the nominal balloon diameter), the balloon body will contact the body lumen wall before the balloon 108 reaches the nominal inflation diameter (also known as the nominal balloon diameter). A hoop strength of the artery, in combination with a low inflation pressure and the inflation algorithm disclosed herein, can therefore keep the balloon 108 at a smaller-than-nominal inflation diameter and can maintain the balloon body in a cylindrical profile. For example, the hoop strength of the renal artery, the inflation pressure, and the inflation algorithm can prevent the compliant balloon 108 from expanding to the nominal inflation diameter (also known as the nominal balloon diameter) of the compliant balloon. In smaller vessels, the balloon 108 may need to be made of excess or thicker material compared to balloons 108 normally intended to accommodate only small body lumens because the balloon 108 must accommodate a wide range of body lumen dimensions, some of which may be beyond the nominal balloon diameter. Accordingly, wrinkles 800 that would otherwise be ironed out due to expansion in larger body lumens can result. More particularly, when the balloon 108 is inflated in the target vessel (also known as body lumen) using the arterial limiting approach, the target vessel can constrain the balloon 108, and thus, the balloon 108 can include several wrinkles 800 at the vessel wall where the excess material folds to accommodate the smaller-than-normal diameter. The compliant balloon 108 can be a Pellethane® balloon having a Shore D durometer of 55 and have a double wall thickness of 0.0004 to 0.0014 inch, e.g., 0.0009 inch, and may include several wrinkles 800.

[0125] Referring to FIG. 8B, a perspective view of a compliant balloon having helical folds is shown in accordance with certain embodiments. The compliant balloon 108 can have a proximal balloon end 802 and a distal balloon end 803. The balloon ends 802, 803 may be ends of cylindrical portions of the balloon 108 that are commonly referred to as legs, necks, or tails. The balloon 108, which may be a compliant balloon or a non-compliant balloon, can have balloon tapered sections 814, 816, commonly referred to as balloon shoulders, extending from the balloon legs 802, 803 to a central, working section 818. The balloon shoulders 814, 816 may be conical, rounded, or have another shape that increases in diameterPOMD04604SEC_WO01 PATENT between a respective balloon leg 802, 803 and the working section 818. The working section 818 can also be referred to as the balloon body 818.

[0126] The working section 818, between the balloon shoulders 814 and 816, is shown in a partially inflated state in FIG. 8B. In the partially inflated state (or the deflated state), the balloon 108 includes several helical folds 808 extending about the longitudinal axis 806. More particularly, the helical folds 808 can be present in the balloon wall when the balloon 108 is not fully inflated, e.g., when the balloon has an inflation diameter below a nominal inflation diameter. The helical folds 808 can extend between the proximal balloon end 802 and the distal balloon end 803. More particularly, each helical fold 808 can have a proximal fold end 810 and a distal fold end 812, and the fold can extend between the fold ends in a helical manner, revolving about the longitudinal axis 806.

[0127] Referring to FIG. 8C, a perspective view of a compliant balloon having longitudinal folds is shown in accordance with certain embodiments. Optionally, the compliant balloon 108 is folded to form several longitudinal folds 822. More particularly, each fold can have a fold edge 824 that extends from the proximal fold end 820 to the distal fold end 826 in a primarily longitudinal direction, parallel to the longitudinal axis 806. The balloon folds can be formed in a wrapping or pleating operation. In the partially inflated state (or the deflated state), the compliant balloon 108 includes several longitudinal folds 822 extending about the longitudinal axis 806. More particularly, the longitudinal folds 822 can be present in the balloon wall when the balloon 108 is not fully inflated, e.g., when the balloon has an inflation diameter below a nominal inflation diameter.

[0128] Referring to FIG. 8D, a cross-sectional view of the compliant balloon 108 having longitudinal folds, introduced in FIG. 8C, is shown in accordance with certain embodiments. The fold edge 824 can be an apex of the fold at which an outward facing surface of the balloon fold meets an inward facing surface of the balloon 108. More particularly, the fold edge 824 can be a visual edge at which the balloon material folds over on itself. The fold edge 824 may not necessarily be a completely straight line, but may be suggestive of a straight, longitudinal line. The balloon 108 can have several folds, and each fold can have a respective fold edge 824. Furthermore, the fold edges 824 can be separated from each other by a clocking angle 832. The clocking angle 832 can be an angle between a first radial line extending from the longitudinal axis 806 through a first fold edge 824 to a second radial line extending from the longitudinal axis 806 through a second fold edge 824. The clocking angle 832 may be consistent over a length of the balloon 108, between thePOMD04604SEC_WO01 PATENT longitudinal folds 822 and / or between the helical folds 808 described below. For example, the clocking angle 832 can be about 120 degrees in the illustrated cross-section, and may be about 120 degrees between the same two folds at other cross-sections along the length of the balloon 108. The several folds of the balloon 108 may include two or more folds. For example, the several folds can include three folds, as shown in FIG. 8D. Alternatively, the folds (either longitudinal or helical) can include two folds, four folds, etc. The several folds may be evenly distributed such that the clocking angle 832 between each pair of folds is the same. For example, when there are four folds the clocking angle 832 can be 90 degrees, when there are three folds the clocking angle 832 can be 120 degrees, when there are two folds the clocking angle 832 can be 180 degrees, etc. Alternatively, the folds may be unevenly distributed and the clocking angle 832 may vary between different pairs of fold edges 804. For example, the balloon 108 may have three folds with a first pair of fold edges 804 separated by 180 degrees, a second pair of fold edges 804 separated by 90 degrees, and a third pair of fold edges 804 separated by 90 degrees. An embodiment having three folds is described herein. Such example, however, is by no way limiting and it will be appreciated that the compliant balloon 108 may have any number of folds.

[0129] Referring to FIG. 8E, a perspective view of a compliant balloon having helical folds is shown in accordance with certain embodiments. In certain embodiments, the several longitudinal folds 822 can be converted into several helical folds 808. Alternatively, the helical folds 808 may be introduced directly into the balloon 108 without the intermediate operation of forming the longitudinal folds 822. In either case, the distal balloon end 803 can be rotated relative to the proximal balloon end 802 to form several helical folds 808 in the balloon 108. Accordingly, formation of the helical folds 808 can include twisting the balloon 108 to create the folds, or folding the balloon and then twisting the balloon to convert the folds from longitudinal folds 822 into helical folds 808. Twisting the balloon 108 can pre-set the balloon material and reduce a profile of the balloon. In certain embodiments, the balloon 108 is twisted by a twist angle that causes the fold edges 804 of the folds to extend helically from the proximal fold end 810 to the distal fold end 812. The folds, therefore, locate the fold edges 804 at predetermined locations around the balloon 108. The folds will remain in these locations when the balloon 108 is inflated and deflated, creating a repeatable distribution of excess balloon material relative to the transducer 214. In the partially inflated state (or the deflated state), the balloon 108 includes several helical folds 808 extending about the longitudinal axis 806. More particularly, the helical folds 808 can be present in thePOMD04604SEC_WO01 PATENT balloon wall when the balloon 108 is not fully inflated, e.g., when the balloon has an inflation diameter below a nominal inflation diameter.

[0130] Referring to FIG. 8F, a cross-sectional view of a balloon having helical folds is shown in accordance with certain embodiments. The helical folds 808 can have a twist angle 852. The twist angle 852 may be defined by an angular displacement between the proximal fold end 810 and the distal fold end 812. The twist angle 852 can be 90 degrees, 120 degrees, 180 degrees, or any other angle. The twist angle 852 may correspond to the clocking angle 832. The illustrated cross-section can be taken at the distal fold end 812, transverse to the longitudinal axis 806, and the proximal fold end 810 may be hidden, in the view of FIG. 8F, behind an adjacent fold. The angular displacement in the illustrated example can be 180 degrees, resulting in the clocking angle 832 of 120 degrees.Accordingly, the twist angle 852 can be greater than the clocking angle 832. In certain embodiments, the twist angle 852 introduces the clocking angle 832, e.g., when the optional operation of forming longitudinal folds 822 is omitted. More particularly, the twisting of the balloon 108 can cause the balloon material to fold over on itself, forming the helical balloon folds. In some cases, the twist angle 852 required to achieve a desired clocking angle 832 may correspond to the clocking angle 832. More particularly, a twist angle 852 of 120 degrees may produce folds having a clocking angle 832 of 120 degrees. Alternatively, the flexibility of the balloon material may require that a larger twist angle 852 be used to achieve the desired clocking angle 832. For example, a twist angle 852 of 180 degrees may be used to produce a clocking angle 832 of 120 degrees. Accordingly, the twist angle 852 can be equal to or greater than the clocking angle 832. For example, the twist angle 852 can be in an angular displacement range including an angle equal to the clocking angle 832 up to an angle equal to five times the clocking angle 832. By way of example, when the clocking angle 832 is 120 degrees, the twist angle 852 can be between 120 degrees to 600 degrees.

[0131] The above description is intended to be illustrative and not limiting. More particularly, the balloon 108 may not require a particular clocking angle 832 or twist angle 852 to provide beneficial function in accordance with the principles described herein. The twist angle 852 can be any angle that distributes excess material of the balloon 108 into helical folds 808 and biases the balloon 108 to a same deflated profile and configuration when the balloon is inflated and deflated. Accordingly, the twist angle 852 can introduce repeatable helical folds 808 in the balloon wall, however, the helical folds 808 may have a clocking angle 832 that is independent of the twist angle 852.POMD04604SEC_WO01 PATENT

[0132] In certain embodiments, the balloon 108 is a compliant balloon. The balloon 108 can include an elastomeric material, as described above. The elastomeric material may, for example, include a low durometer (e.g., Shore 80A-55D) urethane material, as described above. Furthermore, the balloon 108 material may be thin. For example, a double wall thickness of the balloon 108 may be 0.0005 inch to 0.0015 inch. The balloon 108 may therefore be highly flexible and the twisting bias can introduce pleats when the thin, elastomeric material folds over onto itself.

[0133] When the balloon 108 is rotated to induce a twisting bias in the balloon material, the distal balloon end 803 can be connected to, e.g., attached to, mounted on, etc., a distal tip and / or an isolation tube of the catheter shaft 212. The balloon 108 can be sealed to the catheter shaft 212 such that the interior of the balloon 108 contains the ultrasound transducer 214 and can be filled with a cooling fluid to inflate the balloon. The twisting bias of the balloon 108 in the assembled tissue treatment catheter 102 can be beneficial in creating pre-determined folds in the balloon to facilitate predictable balloon deployment. The predetermined folds are predictably and repeatably positioned during inflation and deflation to reduce variation in ultrasound therapy as acoustic energy travels through the balloon wall. Furthermore, the folds can provide a thicker balloon wall around the transducer 214 when the balloon 108 is deflated, thereby enhancing protection of the ultrasound transducer.

[0134] The term folds, as used herein, is meant to also encompass wrinkles, such as the wrinkles 800 described above with reference to FIG. 8A. Accordingly, when referring to the term folds herein, such folds can, for example, be the wrinkles 800 described above with reference to FIG. 8 A, the helical folds 808 described above with reference to FIG. 8B, 8E and 8F, and / or the longitudinal folds 822 described above with reference to FIGS. 8C and 8D, but are not limited thereto.

[0135] In certain embodiments, the balloon 108 can be designed such that folds (e.g., wrinkles) in the balloon do not significantly interfere with energy delivery of the catheter. For example, the folds can have a predictable fold pattern that minimally interferes with energy delivery. More specifically, the predictable fold pattern can have a low density of folds, and / or may have folds that occur in particular locations that are not in the primary energy delivery path.

[0136] In other embodiments, the folds (e.g., 800, 808, and / or 822) can have a predictable fold pattern (e.g., wrinkle pattern) that purposefully interferes with acoustic energy delivery, such that the folds attenuate acoustic energy emitted from the transducer 214POMD04604SEC_WO01 PATENT within the balloon 108 such that a lower amount of acoustic energy is delivered to tissue being treated when the balloon 108 is in apposition with a body lumen wall of a relatively small diameter body lumen segment, compared to when the balloon 108 is in apposition with a body lumen wall of a relatively large diameter body lumen segment. Such embodiments utilize the balloon 108 to help deliver an appropriate amount of acoustic energy to target tissue being treated. More specifically, a compliant balloon, such as the balloons 108 shown in FIGS. 8A-8F, can be designed so that the folds are configured to occur in a predictable manner such that when the compliant balloon 108 is inserted into a body lumen segment and partially inflated to less than its nominal balloon diameter (such that the balloon is in apposition with a body lumen wall of the body lumen segment), the folded (e.g., wrinkled) balloon surface generates additional acoustic reflections compared to when the balloon 108 is inflated to the point that there are no (or less, and / or smaller) folds (e.g., wrinkles). In such embodiments, the folds cause the acoustic waves to travel a longer propagation path before the acoustic waves exit the balloon 108 and reach the target tissue being treated, whereby this increase in the acoustic propagation path inside the balloon results in acoustic energy loss inside the balloon, prior to the acoustic energy exiting the balloon. Additionally, the folds effectively increase the balloon thickness where folds (e.g., wrinkles) reside. Because the thickness of the balloon material affects how much attenuation is caused by the balloon (i.e., the greater the thickness of the balloon material the greater the attenuation caused), the effective increase in the balloon thickness caused by the folds also contributes to the acoustic energy attenuation. Both of these factors cause a higher percentage of acoustic energy loss before the acoustic energy propagates into the target tissue compared to using a balloon of a same size without folds (e.g., without wrinkles).

[0137] More generally, in accordance with certain embodiments, the compliant balloon 108 is designed to at least partially attenuate some of the acoustic energy emitted by the transducer 214 and thereby reduce an amount of the acoustic energy that passes through folded (e.g., wrinkled) balloon material when a diameter of the body lumen segment in which the balloon is inserted is within a smaller diameter subset of a specified range of diameters, compared to when the diameter of the body lumen segment is within a larger diameter subset of the specified range of diameters. For example, less acoustic energy passes through folded (e.g., wrinkled) balloon material when the diameter of the body lumen segment is 3 mm, compared to when the diameter of the body lumen segment is 8 mm. For another example, less acoustic energy passes through folded (e.g., wrinkled) balloon material when thePOMD04604SEC_WO01 PATENT diameter of the body lumen segment is 3 mm, compared to when the diameter of the body lumen segment is 4.9 mm. For still another example, less acoustic energy passes through folded (e.g., wrinkled) balloon material when the diameter of the body lumen segment is 5 mm, compared to when the diameter of the body lumen segment is 8 mm.

[0138] The compliant balloons 108 described herein can be inflated using an arterial limiting approach, a pressure limiting approach, or a hybrid thereof. In the arterial limiting approach, the balloon 108 is inflated to a predetermined inflation pressure, e.g,, 10 psi, or within a range of predetermined inflation pressures, e.g., 9 to 10 psi, regardless of a vessel lumen diameter. More particularly, the low pressure used for the arterial limiting approach can be a fixed pressure, within a certain tolerance, that is used regardless of the vessel lumen diameter. For example, the predetermined inflation pressure can be 11 psi or less, and may be used in any target vessel 302 having a vessel lumen diameter of between 3 and 8.5 mm. It will be appreciated that this inflation paradigm is distinct from the pressure limiting approach, which utilizes inflation pressures based on the lumen diameter that is being targeted.

[0139] Referring to FIG. 9, a diagram of a balloon pressure curve of a compliant balloon 108 being inflated according to a hybrid inflation approach is shown in accordance with certain embodiments. In the hybrid inflation approach, a single, compliant balloon 108 having a nominal inflation diameter can be used to treat vessel lumen diameters smaller than the nominal inflation diameter and larger than the nominal inflation diameter. The compliant balloon 108 can similarly treat the lumen diameters in different vessels, or in different portions of a same vessel, e.g., a distal portion and a proximal portion of the vessel. The balloon 108 may be sized to be at or near a mid-point of a size appropriate for a set of body lumen diameters. For example, with respect to typical renal artery lumen sizes, a balloon 108 having a nominal inflation diameter of 6 to 6.75 mm may be provided.

[0140] The hybrid approach is a combination of the arterial limiting approach and the pressure limiting approach. In the above example of the balloon 108 having the nominal inflation diameter of 6.75 mm, for an artery less than 6.75 mm, the balloon 108 may be inflated to a low working pressure, e.g., 10 psi. Over that working inflation range, the balloon 108 may be in an arterial limiting range of operation 902. In the arterial limiting range of operation, the balloon 108 is arterial limited. Accordingly, when the compliant balloon 108 is inflated to a first working inflation pressure within a renal artery (or renal artery portion) having a first arterial diameter that is smaller than the nominal inflationPOMD04604SEC_WO01 PATENT diameter of the compliant balloon 108, the hoop strength of the renal artery, the inflation pressure, and the inflation algorithm disclosed herein prevents the compliant balloon 108 from expanding to the nominal inflation diameter of the compliant balloon 108.

[0141] By contrast, for an artery (or artery portion) larger than the nominal inflation diameter (e.g., 6.75 mm), the pressure in the balloon 108 can be increased to increase the size of the balloon 108. The balloon 108, when operating above the 6.75 mm nominal inflation diameter, can operate in a pressure limiting range of operation 904. In the pressure limiting range of operation 904, the balloon 108 is pressure limited. Accordingly, when the compliant balloon 108 is inflated to a second working inflation pressure higher than the first working inflation pressure within a renal artery (or renal artery portion) having a second arterial diameter larger than the nominal inflation diameter of the compliant balloon 108, the second working inflation pressure expands the diameter of the compliant balloon 108 to be larger than the nominal inflation diameter of the compliant balloon 108. The working inflation pressure can be gradually increased to expand the balloon 108 into apposition with gradually larger arterial diameters. The 6.75 mm nominal inflation diameter is provided by way of example, and as in the embodiments above, the balloon 108 may have a nominal inflation diameter of 3.5 mm, 3.7 mm, 4.5 mm, 5.5 mm, 6.5 mm, or any other diameter that delineates the arterial limiting range of the balloon 108 from the pressure limiting range of the balloon.

[0142] In certain embodiments, the compliant balloon 108 has a nominal inflation diameter of about 4 mm. When the compliant balloon 108 is inflated to a first working inflation pressure within a first arterial diameter of a renal artery having a diameter less than 4 mm, the hoop strength of the renal artery, the inflation pressure, and the inflation algorithm herein disclosed, prevents the compliant balloon 108 from expanding to a diameter larger than the first arterial diameter of the renal artery. When the compliant balloon 108 is inflated to a second working inflation pressure higher than the first working inflation pressure within a renal artery having a second diameter larger than 4 mm, however, the second working inflation pressure expands the diameter of the compliant balloon 108 to be in apposition with the second diameter of the renal artery.

[0143] As a further example of the hybrid approach, the compliant balloon 108 can be a Pellethane® balloon having a Shore D durometer of 55 and a nominal inflation diameter of 5.5 mm. The compliant balloon 108 can be maintained at a constant low balloon pressure for apposition in smaller arterial diameters, but for incrementally larger arterial diameters, the working pressure is increased to match the balloon size to the artery diameter. Table 1 listsPOMD04604SEC_WO01 PATENT the working balloon pressures used to maintain the balloon diameter size range. Note that the working inflation pressure for diameters up to, and slightly above, the nominal working inflation diameter of the compliant balloon are a single, low pressure of 10 psi. The working inflation pressures then gradually increase to achieve inflation diameters 704 above 6 mm.

[0144] As described above, the working inflation pressure is dependent on the working flowrate of the inflation fluid 306 within the balloon 108. Table 2 provides approximate working flowrate values of three selected pressures from the complete range of 10 to 20 psi that may be used to maintain the diameter of the balloon 108 using a hybrid approach during treatment and / or cooling. Note that the flowrates are around or above 30 mE / min, which has been shown to effectively cool tissue during renal denervation.Table 2. Balloon Flowrate Data

[0145] Example details of the optional cartridge 112 and the reservoir 110, which were introduced above in the above discussion of FIG. 1 , will now be described with reference to FIG. 10. The cartridge 112 and / or reservoir 110 can be parts of a fluid supply subsystem 1130. However, it is noted that alternative fluid supply subsystems can alternatively be used to supply cooling fluid to and circulate cooling fluid through the balloon 108, while still being within the scope of the embodiments of the present technology described herein. Referring to FIG. 10, the reservoir 110 is shown as being implemented as a fluid bag, which can be the same or similar to an intravenous (IV) bag in that it can hang from a hook, or the like. The reservoir 110 and the cartridge 112 can be disposable and replaceable items.POMD04604SEC_WO01 PATENT

[0146] The reservoir 110 is fluidically coupled to the cartridge 112 or a tubing kit via a pair of fluidic paths, one of which is used as a fluid outlet path (that delivers fluid from the reservoir to the cartridge), and the other one of which is used as a fluid inlet path (that returns fluid from the cartridge to the reservoir). In certain embodiments, the cartridge 112 can include a syringe pump, which may include a pressure syringe 1042 A and a vacuum syringe 1042B. The pressure syringe 1042 A includes a barrel 1044A, a plunger 1046 A, and a hub 1048 A. Similarly, the vacuum syringe 1042B includes a barrel 1044B, a plunger 1046B, and a hub 1048B. The hub 1048A, 1048B of each of the syringes 1042A, 1042B is coupled to a respective fluid tube or hose. For example, the pressure syringe 1042 A may be coupled to a supply line 1050 connecting the pressure syringe 1042A to the catheter 102. The cartridge 112 is also shown as including pinch valves VI (catheter outflow valve), V2 (catheter inflow valve) and V3 (reservoir valve), pressure sensors Pl, P2, and P3, and a check valve CV. For example, a supply valve 1052 (V2) may be located in the supply line 1050 such that fluid can be delivered through the supply valve to the supply line. While not specifically shown in FIG. 10, the syringe pump can include one or more gears and step-motors, and / or the like, which are controlled by the controller 104 (in FIG. 1) to selectively maneuver the plungers 1046 A, 1046B of the pressure syringe 1042A and / or the vacuum syringe 1042B. Alternatively, the gear(s) and / or step-motor(s) can be implemented within the controller 104, and can be used to control the syringe pump.

[0147] The fluid supply subsystem 1130 can include a fluid supply actuator 1056. The fluid supply actuator 1056 can be a mechanism used to deliver fluid to the catheter 102 through the supply line 1050. For example, while not specifically shown in FIG. 10, the fluid supply actuator 1056 can include a motor (such as a stepper motor), a hydraulic piston, or another type of actuator to move the plunger 1046 A or otherwise pressurize the fluid within the fluid supply line 1050. The fluid supply actuator 1056 can be controlled by the controller 104 (in FIG. 1) to selectively maneuver the plungers of the syringe pump. Accordingly, the fluid supply actuator 1056 of the fluid supply subsystem 1130 can deliver fluid to the catheter 102 through the supply line 1050.

[0148] In certain embodiments, the fluid supply subsystem 1130 includes a supply pressure sensor 1060 (Pl). The supply pressure sensor 1060 can detect a fluid pressure of the fluid in the supply line 1050. More particularly, when the fluid supply actuator 1056 is actuated to deliver fluid to the catheter 102 through the supply line 1050, the supply pressure sensor 1060 can sense the pressure in the supply line. Accordingly, as described below, thePOMD04604SEC_WO01 PATENT controller 104 can regulate fluid flow rate to achieve an intended fluid pressure that stabilizes balloon pressures during an inflation process.

[0149] The tissue treatment system 100 can include components to facilitate balloon deflation, in addition to balloon inflation. In certain embodiments, the fluid supply subsystem 1130 includes a fluid return actuator 1062. Like the fluid supply actuator 1056, the fluid return actuator 1062 can move fluid between the catheter 102 and the fluid supply subsystem 1130. For example, the fluid return actuator 1062 can move the plunger 1046B of the pressure syringe 1042B to remove fluid from the catheter 102 through a return line 1064. Accordingly, the fluid return actuator 1062 of the fluid supply subsystem 1130 can enable deflation of the balloon under control of the controller 104, as described below.

[0150] In certain embodiments, the fluid supply subsystem 1130 includes a return pressure sensor 1066 (P2). The return pressure sensor 1066 can detect a fluid pressure of the fluid in the return line 1064. More particularly, when the fluid return actuator 1062 is actuated to remove fluid from the catheter 102 through the return line 1064, the return pressure sensor 1066 can sense the pressure in the return line. Accordingly, as described below, the controller 104 can regulate fluid flow rate to achieve an intended fluid pressure that prevents catheter shaft collapse during a deflation process.

[0151] In order to at least partially fill the barrel of the pressure syringe 1042 A with a portion of the cooling fluid that is stored in the reservoir 110, the pinch valves V 1 and V2 are closed, the pinch valve V3 is opened, and the plunger 1046 A of the pressure syringe 1042 A is pulled upon to draw cooling fluid 1013 into the barrel 1044A of the of the pressure syringe 1042A. The pinch valve V3 is then closed and the pinch valves VI and V2 are opened, and then the plunger 1046 A of the pressure syringe 1042 A is pushed upon to expel cooling fluid from the barrel 1044A of the pressure syringe 1042 A through the fluid tube attached to the hub 1048 A of the pressure syringe 1042 A. The cooling fluid expelled from the pressure syringe 1042 A enters the fluid lumen 1070 (in the catheter shaft 212), via the fluidic inlet port 208 of the catheter 102, and then enters and at least partially fills the balloon 108. Simultaneously, the plunger 1046B of the vacuum syringe 1042B can be pulled upon to pull or draw cooling fluid from the balloon into the fluid lumen 1072 (in the catheter shaft), through the fluidic outlet port 210 of the catheter 102, and then through fluid tube attached to the hub 1048B of the vacuum syringe 1042B and into the barrel 1044B of the vacuum syringe 1042B. In this manner, the cooling fluid can be circulated through the balloon 108. ThePOMD04604SEC_WO01 PATENT balloon 108 can be inflated by supplying more cooling fluid to the balloon than is removed from the balloon. One or more of the pressure sensors Pl, P2, and P3 can be used to monitor the pressure in the balloon 108 to achieve a target balloon pressure, e.g., of 10 pounds per square inch (psi), but not limited thereto. Once the balloon is inflated to a target pressure, e.g., between 10 psi and 30 psi, and / or size, the cooling fluid can be circulated through the balloon without increasing or decreasing the amount of fluid within the balloon by causing the same amount of fluid that is removed from the balloon 108 to be the same as the amount of fluid that is provided to the balloon 108. Also, once the target balloon pressure is reached, the ultrasound transducer 214 can be excited to emit ultrasound energy to treat tissue that surrounds the portion of the body lumen (e.g., a portion of a renal artery) in which the balloon 108 and the transducer 214 are inserted. When the ultrasound transducer 214 is emitting ultrasound energy it can also be said that the ultrasound transducer 214 is performing sonication, or that sonication is occurring. Prior to, during, and / or after the sonication, cooling fluid can be circulated through the balloon by continuing to push on the plunger 1046 A of the pressure syringe 1042A and continuing to pull on the plunger 1046B of the vacuum syringe 1042B.

[0152] After the sonication is completed, and the balloon 108 is to be deflated so that the catheter 102 can be removed from the body lumen, the cooling fluid should be returned from the barrel 1044B of the vacuum syringe 1042B to the reservoir 110. In order to return the cooling fluid from the barrel 1044B of the vacuum syringe 1042B to the reservoir 110, the pinch valves VI, V2, and V3 are all closed, and the plunger of the vacuum syringe 1042B is pushed on to expel the cooling fluid out of the barrel of the vacuum syringe 1042B, past the check valve CV, and into the reservoir 110.

[0153] The pressure sensors Pl, P2, and P3 can be used to monitor the fluidic pressure at various points along the various fluidic paths within the cartridge 112, which pressure measurements can be provided to the controller 104 as feedback that is used for controlling the fluid actuators 1056, 1062, and / or the syringe pump, and / or for other purposes, such as, but not limited to, determining the fluidic pressure within the balloon 108. Additionally, flowrate sensors Fl and F2 can be used, respectively, to monitor the flowrate of the cooling fluid that is being injected (also referred to as a pushed, provided, or supplied) into the balloon 108, and to monitor the flowrate of the cooling fluid that is being drawn (also referred to as a pulled or removed) from the balloon 108. The pressure measurements obtained from the pressure sensors Pl, P2, and P3 can be provided to the controller 104 soPOMD04604SEC_WO01 PATENT that the controller 104 can monitor the balloon pressure. Additionally, flowrate measurements obtained from the flowrate sensors Fl and F2 can be provided to the controller 104 so that the controller 104 can monitor the flowrate of cooling fluid being pushed into and pulled from the balloon 108. It would also be possible for one or more pressure sensors and / or flowrate sensors to be located at additional or alternative locations along the fluidic paths that provide cooling fluid to and from the balloon 108.

[0154] FIG. 11 A will now be used to describe an example implementation of the controller 104 of the tissue treatment system 100, which was introduced in FIG. 1. Referring to FIG. 11 A, the controller 104 is shown as including one or more processing devices 1112, a memory 1114, a user interface 1116, and an ultrasound excitation source 1118, but can include additional and / or alternative components. While not specifically shown, a processing device 1112 can be located on a control board, or more generally, a printed circuit board (PCB) along with additional circuitry of the controller 104. The processing device 1112 can be operatively and communicatively coupled with the memory 1114 and the excitation source 1118. The memory 1114 may, for example, include a non-transitory computer-readable medium storing instructions. The processing device 1112 can execute the instructions to cause the tissue treatment system 100 to perform the methods described herein. The user interface 1116 interacts with the processing device 1112 to cause transmission of electrical signals at selected actuation frequencies to the ultrasound transducer 214 via wires of the connection cable 106 and the cabling 216 that extends through the catheter shaft 212. These wires electrically couple the controller 104 to the transducer 214 so that the controller 104 can send electrical signals to the transducer 214, and receive electrical signals from the transducer 214. The processing device 1112 can control the ultrasound excitation source 1118 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 214. More generally, the excitation source 1118 can provide energy to the ultrasound transducer 214 of the catheter 102 and, therefore, the controller 104 can control one or more ultrasound treatment parameters that are used to perform sonication. In certain embodiments, the excitation source 1118 can also detect electrical signals generated by transducer 214 and communicate such signals to the processing device 1112 and / or circuitry of a control board. While the ultrasound excitation source 1118 in FIG. 11A is shown as being part of the controller 104, it is also possible that the ultrasound excitation source 1118 is external to the controller 104POMD04604SEC_WO01 PATENT while still being controlled by the controller 104, and more specifically, by the processing device 1112 of the controller 104.

[0155] The user interface 1116 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 / retrieval unit (not shown), and / or otherwise communicate with the processing device 1112. The user interface 1116 can include a voice-activated mechanism to enter patient data or may be able to communicate with additional equipment so that control of the controller 104 is through a separate user interface, such as a wired or wireless remote control. In some embodiments, the user interface 1116 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 1116 provides a graphical user interface (GUI) that instructs a user how to properly operate the system 100. The user interface 1116 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.

[0156] The controller 104 can also control the cooling fluid supply subsystem 1130, which can include the cartridge 112 and reservoir 110, which were described above with reference to FIGS. 1 and 10, but can include alternative types of fluid pumps, and / or the like. For example, the fluid supply subsystem 1130 can include the fluid supply actuator 1056 and / or the fluid return actuator 1062 to deliver fluid to or remove fluid from the catheter 102. The cooling fluid supply subsystem 1130 is fluidically coupled to one or more fluid lumens (e.g., 1070 and 1072) within catheter shaft 212 which in turn are fluidically coupled to the balloon 108. The cooling fluid supply subsystem 1130 can be configured to circulate a cooling liquid through the catheter 102 to the transducer 214 in the balloon 108. The cooling fluid supply subsystem 1130 may include elements such as a reservoir 110 for holding the cooling fluid 1013, pumps (e.g., syringes 1042A and 1042B), a refrigerating coil (not shown), or the like for providing a supply of cooling fluid to the interior space of the balloon 108 at a controlled temperature, desirably at or below body temperature. The processing device 1112 interfaces with the cooling fluid supply subsystem 1130 to control the flow of cooling fluidPOMD04604SEC_WO01 PATENT into and out of the balloon 108. For example, the processing device 1112 can be communicatively coupled to the fluid supply subsystem 1130, and can be operatively and communicatively coupled with the memory 1114 storing instructions which, when executed by the processing device 1112, causes the tissue treatment system 100 to perform the methods described herein. More particularly, the processing device 1112 can control actuator (e.g., motor) control devices linked to drive actuators (e.g., motors) associated with pumps for controlling the speed of operation of pumps (e.g., syringes 1042A, 1042B). Such actuator control devices can be used, for example, where the pumps are positive displacement pumps, such as peristaltic pumps. Alternatively, or additionally, a control circuit may include structures such as controllable valves connected in the fluid circuit for varying resistance of the circuit to fluid flow (not shown). The processing device 1112 can monitor pressure measurements obtained by the pressure sensors (e.g., Pl, P2 and P3) to monitor and control the cooling fluid through the catheter 102 and the balloon 108. The pressure sensors can also be used to determine if there is a blockage and / or a leak in the catheter 102. While the balloon 108 is in an inflated state, the pressure sensors can be used to maintain a desired pressure in the balloon 108, e.g., at a pressure of between 10 psi and 30 psi, but not limited thereto. As will be described in additional detail below, the processing device 1112 can use sensor measurements from one or more of the pressure sensors and / or other sensors to determine when the balloon 108 is in apposition with a body lumen as well as to estimate an inner diameter of a body lumen in order to select an appropriate dose of ultrasound energy to be delivered to treat tissue surrounding the body lumen.

[0157] FIG. 1 IB is used to describe example details of the ultrasound excitation source 1118, according to certain embodiments of the present technology. Where the ultrasound excitation source 1118 is used to produce signals that are used to drive the transducer 214 of the catheter 102, the ultrasound excitation source 1118 can also be referred to as a signal generator 1118. As shown in FIG. 1 IB, the ultrasound excitation source 1118 (also known as signal generator 1118) is communicatively coupled to the processing device(s) 1112 of the controller 104. The ultrasound excitation source 1118 (also known as signal generator 1118) is shown as including a pulse generator 1132, a power amplifier 1134, a bi-directional coupler 1136, an output transformer 1138, and an output filter 1140. The ultrasound excitation source 1118 (also known as signal generator 1118) is also shown as including a digital-to-analog converter (DAC) 1142 and a power supply 1144, which arePOMD04604SEC_WO01 PATENT collectively used to control a gain of the power amplifier 1134. The pulse generator 1132 generates signal pulses under the control of at least one of the processing device(s) 1112. More specifically, at least one of the processing device(s) 1112, or a tissue treatment control module 1156 thereof, controls the timing and frequency of pulses generated by the pulse generator 1132.

[0158] In certain embodiments, the gain of the power amplifier and / or the energy provided to the tissue treatment catheter 102 is controlled in part by a DAC count of the DAC 1142. More generally, the DAC count of the excitation source 1118, which can be determined and sent to the DAC 1142 by the processing device 1112, can relate to the power output of the transducer 214. The DAC count refers to the digital value that the DAC converts into an analog voltage to control the output of the excitation source 1118. The DAC count can be determined by the resolution of the DAC, which is often specified in bits. For example, an 8-bit DAC can produce 256 discrete output levels (from 0 to 255), while a 12-bit DAC can produce 4096 levels (from 0 to 4095). By adjusting the DAC count of the excitation source 1118, the controller 104 dynamically adjusts the output energy supplied to the transducer 214, which in turn adjusts the power output from the transducer 214 to the target tissue.

[0159] The pulses generated by the pulse generator 1132 are amplified by the power amplifier 1134 to produce amplified pulses that are provided to the output transformer 1138. The output transformer 1138 steps-up the voltage of the pulses output by the power amplifier 1134, and also electrically isolates the circuitry and other components that are downstream of the output transformer 1138, such as the transducer 214, from the circuitry that is upstream of the output transformer 1138, such as the power amplifier 1134 and the pulse generator 1132. For example, the output transformer 1138 can step-up pulses having a peak-to-peak amplitude of 24V, to pulses having a peak-to-peak amplitude of 60V or 70V but is not limited thereto. The output filter 1140 shapes the output signal that is provided to the transducer 214, e.g., to convert square wave pulses to sinusoidal pulses, but not limited thereto. The output filter 1140 can also remove noise introduced by the output transformer 1138.

[0160] The bi-directional coupler 1136, which is located within the signal path between the power amplifier 1134 and the transducer 214, provides a signal indicative of (e.g., proportional to) forward power provided to the transducer 214, and a signal indicative of (e.g., proportional to) reflected power from the transducer 214. In FIG. 11B the bi-POMD04604SEC_WO01 PATENT directional coupler 1136 is shown as being coupled between the power amplifier 1134 and the output transformer 1138. In alternative embodiments, the bi-directional coupler 1136 can be located downstream of the output transformer 1138, and thus, closer to the transducer 214. A return electrical signal 1190 can include one or more of a signal indicative of forward power provided to the transducer 214, e.g., a forward power signal, and a signal indicative of reflected power from the transducer 214, e.g., a reflected power signal. The return power signal 1190 components can be converted from analog signals to digital signals by analog-to- digital converter (ADC) 1152 and ADC 1154, and may be used as feedback signals that are provided to at least one of the processing device(s) 1112 to control tissue treatment delivered by the transducer 214. Such feedback is used to accurately control the power provided to the transducer 214, as described herein with respect to FIGS. 23-32.

[0161] In certain catheter-based tissue treatment systems that utilize ultrasound transducers, a user of such a system is required to determine an accurate estimate of a diameter of a body lumen into which a catheter including an ultrasound transducer is to be inserted, so that an appropriate one of numerous (e.g., six) different catheters having an appropriately sized one of numerous (e.g., six) different balloons can be selected for use, and so that an appropriate amount of numerous (e.g., six) different possible amounts of acoustic energy is selected for emission (e.g., in terms of six different power settings). Accordingly, existing catheter-based systems require significant shelf space to stock the portfolio of device sizes. Additionally, the costs of stocking the portfolio of device sizes can be high. The large product portfolio also creates manufacturing complexities associated with producing a wide range of different device models. Additionally, the need to accurately estimate a diameter of a body lumen increases the time and complexity of a tissue treatment procedure that utilizes such catheter-based tissue treatment systems. The above summarized catheter-based tissue treatment systems can be referred to herein as prior catheter-based tissue treatment systems.

[0162] Certain embodiments of the present technology described herein simplify tissue treatment systems and methods (also known as procedures) by eliminating the need for a user to accurately estimate a diameter of a segment of body lumen into which a catheter is being inserted, as well as by eliminating the need for multiple catheters to be produced by a manufacturer and purchased and stocked by a medical facility. More specifically, in certain embodiments, about a same amount of acoustic energy is emitted by an ultrasound transducer of the catheter when a diameter of a segment (also known as portion) of the body lumen (within which the ultrasound transducer is located) is within the specified range of diametersPOMD04604SEC_WO01 PATENT that is at least 4 mm, or at least 5 mm. In other words, so long as the diameter of the segment of the body lumen (within which the ultrasound transducer is located) is within a specified range of expected diameters, e.g., between about 3 mm and 8 mm, then about a same amount of acoustic energy is emitted by the ultrasound transducer of the catheter to treat target tissue surrounding the body lumen in which the ultrasound transducer of the catheter is located. This significantly simplifies the design of the tissue treatment system that includes a catheter, an excitation source (also known as signal generator), and a controller. Additionally, this significantly simplifies the tissue treatment procedure by simplifying what steps need to be performed by a user of the tissue treatment system, in part because the user need not accurately estimate the diameter of the body lumen, and the user need not select from among multiple different catheters to use for the procedure. This also significantly reduces the number of catheters that a manufacturer needs to manufacture, and that a medical facility needs to purchase and stock. The embodiments just summarized can be referred to herein as the single power embodiments.

[0163] In certain embodiments, about a same amount of acoustic energy is emitted by an ultrasound transducer of the catheter when a diameter of a segment (also known as portion) of the body lumen (within which the ultrasound transducer is located) is within the specified range of diameters that is at least 4 mm, or at least 5 mm, while maintaining a total ablation area and depth of ablation to prevent vessel wall damage, in particular damage to the endothelial and medial layers of the vessel wall, while allowing sufficient arterial nerve and / or peri-arterial nerve damage to be therapeutic. A minimum ablation distance from the arterial lumen (e.g., about 0.5 mm to about 1.5 mm) is maintained to preserve the arterial wall, while a maximum ablation distance is maintained to preserve the safety of periarterial organs. For example, a lesion depth of 5 mm-7 mm, e.g., 5.5 mm to 6 mm, may be maintained over the specified range of diameters that is at least 4 mm, or at least 5 mm, or at least 6 mm.

[0164] In other embodiments, rather than about a same amount of acoustic energy always being emitted by the ultrasound transducer of the catheter, a first amount of acoustic energy is emitted by the ultrasound transducer when a diameter of the segment of the body lumen (within which the ultrasound transducer is located) is within a lower subrange of a specified range of diameters (that is at least 1 mm, or at least 1.5 mm, or at least 2 mm, or at least 2.5 mm), and a second amount of acoustic energy (which is greater than the first amount of energy) is emitted by the ultrasound transducer when the diameter of the segment of thePOMD04604SEC_WO01 PATENT body lumen (within which the ultrasound transducer is located) is within an upper subrange of the specified range of diameters (that is at least 2.5 mm, or at least 3 mm, or at least 3.5 mm, or at least 4 mm, or at least 4.5 mm). Such embodiments can be referred to herein as the two power embodiments. While not quite as simple as the single power embodiments, the two power embodiments still significantly simplify the design, manufacture and use of a tissue treatment system that includes a catheter, an excitation source, and a controller, compared to the prior catheter-based tissue treatment systems summarized above (where there was a need to determine an accurate estimate of a diameter of a body lumen into which a catheter is to be inserted, so that an appropriate one of numerous (e.g., six) different catheters having an appropriately sized one of numerous (e.g., six) different balloons can be selected for use, and so that an appropriate amount of numerous (e.g., six) different possible amounts of acoustic energy is selected for emission). Advantageously, the two power embodiment provides a total ablation area and depth of ablation that prevents vessel wall damage, in particular damage to the endothelial and medial layers of the vessel wall, while allowing sufficient arterial nerve damage and / or peri-arterial nerve damage to be therapeutic. A minimum ablation distance from the arterial lumen (e.g., about 0.5 mm to about 1.5 mm) is maintained to preserve the arterial wall, while a maximum ablation distance is maintained to preserve the safety of periarterial organs. For example, a lesion depth of 5 mm-7 mm, e.g., 5.5 mm to 6 mm) may be maintained over the entire range of diameters treated by a two power embodiment. A benefit of the two power embodiment over the one power embodiments is that the two power embodiments should be able to provide safe and effective tissue treatment over a larger range of body lumen diameters than the one power embodiments, because a lower power is used with a smaller diameter subrange of body lumen diameters, and a larger power is used with a larger diameter subrange of body lumen diameters.

[0165] A tissue treatment system, of the single power embodiments and two power embodiments, includes a catheter, a controller (also known as a control unit), and an excitation source (also known as a signal generator). For the following discussion, it is assumed that the tissue treatment system 100 is utilized, which includes the catheter 102, the controller 104, and the excitation source 1118. Further, it is assumed that the catheter includes a distal portion (e.g., the shaft 212) on which is located the ultrasound transducer 214, wherein the catheter is configured such that at least the distal portion of the catheter is insertable into a body lumen (e.g., a renal artery) having a specified range of diameters that isPOMD04604SEC_WO01 PATENT at least 4 mm, or at least 5 mm (e.g., from about 3.0 mm to about 8.0 mm). However, it should be noted that the use of alternative catheters, controllers, excitation sources, and transducers is also possible. The excitation source 1118 is configured to selectively provide energy to the ultrasound transducer 214 of the catheter 102, in response to which the ultrasound transducer 214 emits an acoustic signal having an acoustic frequency, power and duration. The controller 104 is communicatively coupled to the excitation source 1118 and is configured to control the excitation source 1118 to cause the ultrasound transducer 214 to emit about a same amount of acoustic energy when a diameter of the body lumen (e.g., a renal artery) is within the specified range of diameters that is at least 4 mm, or at least 5 mm. An example of the specified range of diameters is from about 3.0 mm to about 8.0 mm, but is not limited thereto.

[0166] In certain embodiments, the specified range of diameters, which is at least 4 mm, or at least 5 mm, includes a lower end of the specified range of diameters and an upper end of the specified range of diameters. In certain such embodiments, the lower end of the specified range of diameters comprises one of about 2.0 mm, about 2.5 mm, or about 3.0 mm, and the upper end of the specified range of diameters comprises one of about 7.5 mm, about 8.0 mm, or about 8.5 mm. Accordingly, the specified range of diameters can be, e.g., from about 2.0 mm to about 7.5 mm, from about 2.0 mm to about 8.0 mm, from about 2.0 mm to about 8.5 mm, from about 2.5 mm to about 7.5 mm, from about 2.5 mm to about 8.0 mm, from about 2.5 mm to about 8.5 mm, from about 3.0 mm to about 7.5 mm, from about 3.0 mm to about 8.0 mm, or from about 3.0 mm to about 8.5 mm. Other variations are also possible and within the scope of embodiments described herein. The term “about,” when used herein to specify a value, means the value + / - 10 percent of the value, e.g., “about 3 mm” means 3 mm + / - 0.3 mm, and “about 8 mm” means 8 mm + / - 0.8 mm.

[0167] The amount of acoustic energy emitted by the ultrasound transducer 214 that enters target tissue surrounding the body lumen in which the ultrasound transducer 214 is located is equal to an Acoustic Entry Power multiplied by a duration (T) that the acoustic signal is emitted. The Acoustic Entry Power is based on (also known as is dependent on) various factors, including an output power level setting of the excitation source (e.g., 1118), a power efficiency of the system (including the components thereof), a frequency of the acoustic signal emitted by the ultrasound transducer 214, a duration (T) of the acoustic signal emitted by the ultrasound transducer, and an amount of attenuation caused by a medium that is between the ultrasound transducer and the body lumen wall. Where the ultrasoundPOMD04604SEC_WO01 PATENT transducer 214 is located within a balloon 108 through which a cooling fluid (e.g., water, sterile water, saline, or D5W) is circulated, the cooling fluid and the balloon material (and potentially, any folds in the balloon material) are the medium between the ultrasound transducer 214 and the body lumen wall. Where the catheter is balloonless (i.e., devoid of a balloon), then blood traveling through the body lumen is the medium between the ultrasound transducer and the body lumen wall. The catheter can include a centering mechanism configured to center the ultrasound transducer within the body lumen. In certain embodiments, the centering mechanism is provided by a compliant balloon 108. Alternatively, or additionally, the centering mechanism can comprise one or more flexible baskets attached to a catheter shaft (e.g., 212), or other structures, such as the spiral springs, but is not limited thereto.

[0168] In other words, the total energy absorbed (Eeg) by the targeted patient tissue (also known as the target tissue, the target zone, or the targeted region) surrounding a body lumen (within which the ultrasound transducer 214 is positioned) is the product of an Entry Acoustic Energy (Eo) multiplied by a portion (J3) (e.g., percent) of the energy used for ablation in the targeted region, wherein the portion QJ) (e.g., percent) of energy used for ablation in the targeted region is dependent on the extent of attenuation caused by the medium between the ultrasound transducer and the body lumen wall. More specifically,, where a is the attenuation coefficient (neper / MHz / cm), f> the portion (e.g., percent) of energy used for ablation in the targeted region, f is the acoustic frequency, and d is the desired outer lesion boundary (also known as lesion depth). The total energy absorbed (Eeg in the targeted region can also be referred to herein as the effective energy (Eeff .

[0169] The Acoustic Entry Energy (Eo) is the total acoustic power delivered into patient tissue, e.g., through a balloon wall. As the acoustic waves propagate through patient tissue, acoustic power is attenuated and converted into heat, which results in a temperature increase in the tissue. Only a portion (J3) (e.g., percent) of the Acoustic Entry Energy (Eo) is absorbed by the targeted region, while the residual portion travels further and is absorbed by untargeted patient tissue beyond the targeted region. As a reminder, energy (such as Acoustic Entry Energy, Eo) is the product of power (such as Acoustic Entry Power, Po) multiplied by time (also known as duration). Thus, the effective energy (Ee), which is the portion of acoustic energy absorbed by the targeted region, is equal to the product of fl multiplied by thePOMD04604SEC_WO01 PATENTAcoustic Entry Energy (Eo), i.e.,as was noted above. The value of can depend on various different parameters, such as, but not limited to, an acoustic frequency and a desired lesion depth d.

[0170] To keep (also known as maintain) the same lesion boundary d (also known as lesion depth), Ee^ should be kept constant. This statement is true when the treatment time (also known as duration) T does not change significantly, and when an impact from heat conduction does not change significantly. It is noted that more total energy or effective energy is required if the treatment time (also known as duration) T is increased significantly to compensate for the heat loss due to conduction. Table 3 below shows the Acoustic Entry Power for various different ultrasound frequencies, assuming a desired lesion depth (d) of 4 mm, and a treatment duration (T) of 7 seconds.Table 3. Acoustic Entry Power Data

[0171] Table 4 below shows the Acoustic Entry Power for various different ultrasound frequencies, assuming a desired lesion depth (d) of 6 mm, and a treatment duration (T) of 7 seconds. As can be appreciated from a comparison between Table 4 and Table 3, using a frequency of 9 MHz, a higher Acoustic Entry Power of 34.6W should be used when there is a desire to produce a lesion depth of 6 mm, compared to an Acoustic Entry Power of 26.0W that may be used where the desired lesion depth is 4 mm (as may be appropriate more distal, i.e., closer to the kidneys).Table 4. Acoustic Entry Power DataPOMD04604SEC_WO01 PATENT

[0172] Table 5 below shows the Acoustic Entry Power for various different ultrasound frequencies, assuming a desired lesion depth (d) of 6 mm, and a treatment duration (T) of 10 seconds. As can be appreciated from a comparison between Table 5 and Table 4, a lower Entry Power of 24.2W should be used when there is a desire to produce a lesion depth of 6 mm where the duration that the Acoustic Entry Power is delivered is 10 seconds, compared to an Acoustic Entry Power of 34.6W that may be delivered for a shorter duration of 7 seconds to produce the same desired lesion depth of 6 mm.Table 5. Acoustic Entry Power Data

[0173] In certain single power embodiments, the controller 104 is configured to control the excitation source to cause the ultrasound transducer 214 to emit the same amount of acoustic energy (when the diameter of the segment of the body lumen, within which the ultrasound transducer is located, is within the specified range of diameters) by controlling the excitation source 1118 so that the output power level setting is about the same, the frequency of the acoustic energy emitted by the transducer 214 is about the same (e.g., about 9 MHz), and the duration of the acoustic energy emitted by the transducer 214 is about the same (e.g.,POMD04604SEC_WO01 PATENT about 7 seconds). In certain such embodiments, a frequency of the acoustic energy is about 9 MHz, the duration of the acoustic power delivery is about 7 seconds, and the Acoustic Entry Power is about 34.6 W. In certain single power embodiments, the catheter 102 includes a balloon 108 in which is located the ultrasound transducer 214, wherein the balloon 108 may be a compliant balloon, example details of which were described above with reference to FIGS. 5-9. In other single power embodiments the catheter is balloonless.

[0174] For Tables 3, 4 and 5, the values shown therein are example values for a tissue treatment system 100 where the ultrasound transducer 214 is located within a balloon 108 through which a cooling fluid is circulated. As noted above, where the catheter is balloonless (i.e., devoid of a balloon), blood traveling through the body lumen is the medium between the ultrasound transducer and the body lumen wall. By contrast, when the catheter includes a balloon 108 within which is located the ultrasound transducer 214, the medium between the ultrasound transducer 214 and the body lumen wall is the cooling fluid (being circulated through the balloon 108) and the balloon material (from which the balloon 108 is made). The attenuation coefficient of blood is greater (e.g., at least lOx greater) than the attenuation coefficient of a typical cooling fluid, and thus, the values shown in the Tables 3, 4 and 5 would differ for balloonless embodiments.

[0175] Where the catheter 102 includes a balloon 108 within which is located the ultrasound transducer 214, the tissue treatment system 100 can also include a fluid supply subsystem 1130 that is configured to circulate cooling fluid through the balloon 108, and the controller 104 can be configured to control the fluid supply subsystem 1130. In such a system, the amount of Acoustic Entry Power is also based on a flowrate of the cooling fluid circulated through the balloon 108. In certain single power embodiments, the controller 104 can be configured to control the fluid supply subsystem 1130 so that the flowrate of the cooling fluid circulated through the balloon is the same when the diameter of the body lumen is within the specified range of diameters (e.g., from about 3 mm to about 8 mm). The flowrate of the cooling fluid circulated through the balloon 108 can be, e.g., within a flowrate range of about 5 mL / min to about 40 mL / min, and in a specific embodiment is in a flowrate range of about 10 mL / min to about 15 mL / min. Unless stated otherwise, it is assumed that a temperature of the cooling fluid is a room temperature of the room where the tissue treatment system 100 is located, however it is also possible that the temperature of the cooling fluid can be modified if so desired, e.g., using a cooling element, or the like.POMD04604SEC_WO01 PATENT

[0176] It has been found advantageous to configure the controller 104 to control the fluid supply system 1130 to circulate the fluid through the balloon 108 a predetermined amount of time after at least the first amount of energy has been emitted by the ultrasound transducer 214. When the energy emission is stopped, the fluid supply system 1130 may thus continue to operate for a predetermined amount of time so as to ensure an efficient cooling and avoid undesired clinical outcomes (e.g., in terms of lesion depths). The predetermined amount of time may be within a range of 0.5 secs to 20 secs, such as 2 secs to 12 secs, in particular 5 secs to 9 secs. While such a “post-emission cooling” is particularly useful for system operation in the lower subrange, the controller 104 could also be configured to control the fluid supply system 1130 to circulate the fluid through the balloon 108 a predetermined amount of time after at least the second amount of energy has been emitted by the ultrasound transducer 214 (i.e., upon system operation in the upper subrange). When the energy emission for the upper subrange is stopped, the fluid supply system 1130 may thus continue to operate for a predetermined amount of time. The predetermined amount of time is within a range of 0.5 secs to 20 secs, such as 2 secs to 12 secs, in particular 5 secs to 9 secs. Such a “post-emission cooling” can also be applied in the context of the single-power strategy.

[0177] FIG. 12A is a graph of Acoustic Entry Power in watts (W) versus body lumen size in millimeters (mm), corresponding to an example implementation of the single power embodiments. The straight line 1202 in FIG. 12 A illustrates the Acoustic Entry Power (W) remaining about the same over the range of body lumen diameters from about 3.0 mm to about 8.0 mm, and the dashed lines 1204 corresponds to a variation of + / - 10%. So long as the Acoustic Entry Power remains within the dashed lines 1204 (e.g., in view of uncertainties such as tolerances) it can be said that the Acoustic Entry Power remains about the same, and more specifically, remains about 34.6 W.

[0178] FIG. 12B is a graph of Acoustic Entry Power in watts (W) versus body lumen size in millimeters (mm) corresponding to another example implementation of the single power embodiments. The curved line 1212 in FIG. 12B illustrates how the acoustic power may be lower for smaller body lumen diameters than for larger body lumen diameters over the range of body lumen diameters from about 3.0 mm to about 8.0 mm, and the dashed lines 1214 corresponds to a variation of + / - 10%. For the graph of FIG. 12B it is assumed that the ultrasound transducer 214 is located within a compliant balloon 108, e.g., a balloon comprising Pellethane having a Shore D durometer of 55 and having a nominal balloon diameter (e.g., of 6.5 mm) and a corresponding nominal balloon wall thickness. InPOMD04604SEC_WO01 PATENT accordance with certain embodiments, a compliant balloon disclosed in U.S. Patent Application No. 17 / 812,884, filed July 15, 2022, titled “Catheter Having Compliant Balloon,” published as US 2023 / 0026169, which is incorporated herein by reference, may be used. In accordance with certain embodiments, a balloon, such as a balloon disclosed in U.S. Patent Application No. 17 / 812,884 that includes several helical folds extending about the ultrasound transducer between the proximal balloon end and the distal balloon end, and being held in place by the torsion member, such as disclosed in U.S. Provisional Patent Application No. 63 / 482,463, titled “Tissue Treatment Catheter Having Torsion Member,” filed January 31, 2023, may be used.

[0179] In FIG. 12B, the acoustic power may be lower for smaller body lumen diameters due to one or more folds in the compliant balloon 108, which one or more folds is / are present when the compliant balloon 108 is partially inflated such that its diameter is less than a nominal balloon diameter (e.g., of 6.5 mm) of the compliant balloon 108, at least partially attenuating some of the acoustic power emitted by the ultrasound transducer 214. This can reduce an amount of the acoustic power that passes through balloon 108 when a diameter of the body lumen in which the compliant balloon 108 is in apposition is within a smaller diameter subset (e.g., from about 3.0 mm to about 6.5 mm) of the specified range of diameters (e.g., from about 3.0 mm to about 8.0 mm), compared to when the compliant balloon 108 is inflated such that its diameter is at least the nominal balloon diameter (e.g., of 6.5 mm) of the compliant balloon 108 and the diameter of the body lumen in which the compliant balloon 108 is in apposition is within a larger diameter subset (e.g., from about 6.5 mm to about 8 mm) of the specified range of diameters (e.g., from about 3.0 mm to about 8.0 mm). More specifically, the aforementioned folds (e.g., wrinkles) in the compliant balloon 108 can increase reflections and / or scattering of ultrasound signals emitted by the ultrasound transducer 214, which increases a propagation length that the ultrasound signals travel before exiting the balloon 108 and entering target tissue surrounding the body lumen. Additionally, the folds effectively increase the balloon thickness where folds (e.g., wrinkles) reside.Because the thickness of the balloon material affects how much attenuation is caused by the balloon (i.e., the greater the thickness of the balloon material the greater the attenuation caused), the effective increase in the balloon thickness caused by the folds also contributes to the acoustic power attenuation. Both of these factors cause a higher percentage of acoustic power loss before the acoustic power propagates into the target tissue compared to using a balloon of a same size without folds (e.g., without wrinkles). Examples of the folds (alsoPOMD04604SEC_WO01 PATENT known as wrinkles) in the compliant balloon 108 are shown in and described above with reference to FIGS. 8A-8F. Certain embodiments take advantage of the folds to help deliver appropriate amounts of acoustic power to tissue being treated.

[0180] More generally, the folds (e.g., 800, 808, and / 822, but not limited thereto) in the compliant balloon 108, which are present when the compliant balloon is partially inflated such that its diameter is less than the nominal balloon diameter of the compliant balloon, are configured to attenuate more of the acoustic power emitted by the ultrasound transducer, and thereby are configured to allow less of the acoustic power to pass through the compliant balloon 108 when the compliant balloon is in apposition with a body lumen segment having a diameter that is within a lower diameter subset (e.g., below 5 mm) of the specified range of diameters, compared to when the compliant balloon is in apposition with a body lumen segment that is within a larger diameter subset (e.g., equal to or greater than 5 mm) of the specified range of diameters.

[0181] In certain embodiments, the compliant balloon 108 stretches when the compliant balloon 108 is inflated beyond the nominal balloon diameter (e.g., of about 6.5 mm), which causes a balloon wall thickness to get thinner than the nominal balloon wall thickness. This can result in less attenuation of the acoustic power emitted by the ultrasound transducer 214 when a diameter of the body lumen in which the compliant balloon 108 is in apposition with a body lumen whose diameter is within a larger diameter subset of the specified range of diameters, compared to when the diameter of the body lumen in which the compliant balloon 108 is in apposition is within a lower diameter subset of the specified range of diameters. In other words, another reason that the Acoustic Entry Power may be greater for larger body lumen sizes, compared to smaller body lumen sizes, is that a balloon wall thickness may be reduced the more the balloon is inflated, with the reduced wall thickness causing less attenuation to acoustic power.

[0182] FIG. 13A is a graph of Acoustic Entry Power in watts (W) versus body lumen size in millimeters (mm), corresponding to an example implementation of the two power embodiments. The stepped line 1302 in FIG. 13A illustrates the Acoustic Entry Power (W) being at about a first magnitude (e.g., about 32.0W) when the diameter of the body lumen is within the lower subrange of diameters from about 3.0 mm to about 4.9 mm, and Acoustic Entry Power (W) being at about a second magnitude (e.g., about 35.8 W) when the diameter of the body lumen is within the upper subrange of diameters from about 5.0 mm to about 8.0POMD04604SEC_WO01 PATENT mm, and the dashed lines 1304 corresponds to a variation of + / - 10% (e.g., in view of uncertainties such as tolerances).

[0183] FIG. 13B is a graph of Acoustic Entry Power in watts (W) versus body lumen size in millimeters (mm) corresponding to another example implementation of the two power embodiments. The curved line 1312 in FIG. 13B illustrates how the acoustic power may be lower for smaller body lumen diameters than larger lumen diameters within the lower subrange of diameters from about 3.0 mm to about 4.9 mm, and may be lower for smaller body lumen diameters than larger lumen diameters within the upper subrange of diameters from about 5.0 mm to about 8.0 mm. The dashed lines 1314 corresponds to a variation of + / - 10%. For the graph of FIG. 13B it is assumed that the ultrasound transducer 214 is located within a compliant balloon 108 having nominal balloon diameter (e.g., of 6.75 mm) and a corresponding nominal balloon wall thickness.

[0184] For similar reasons to those described above with reference to FIG. 12B, the acoustic power may be lower for smaller body lumen diameters than larger lumen diameters within the lower subrange of diameters from about 3.0 mm to about 4.9 mm due to one or more folds in the compliant balloon 108, which is / are present when the compliant balloon 108 is partially inflated such that its diameter is less than a nominal balloon diameter (e.g., of 6.5 mm) of the compliant balloon 108, at least partially attenuating some of the first amount of acoustic power emitted by the ultrasound transducer 214. Similarly, the acoustic power may be lower for smaller body lumen diameters than larger lumen diameters within the upper subrange of diameters from about 5.0 mm to about 8.0 mm due to one or more folds in the compliant balloon 108, which one or more folds is / are present when the compliant balloon 108 is partially inflated such that its diameter is less than a nominal balloon diameter (e.g., of 6.5 mm) of the compliant balloon 108, at least partially attenuating some of the second acoustic power emitted by the ultrasound transducer 214. This is because, as explained above, the folds can increase reflections and / or scattering of ultrasound signals emitted by the ultrasound transducer 214, which increases a propagation length that the ultrasound signals travel before exiting the balloon 108 and entering target tissue surrounding the body lumen. Additionally, the folds effectively increase the balloon thickness where folds (e.g., wrinkles) reside. As noted above, another reason that the Acoustic Entry Power may be greater for larger body lumen sizes, compared to smaller body lumen sizes, is that a balloon wall thickness may be reduced the more the balloon is inflated past its nominal inflation diameter, with the reduced wall thickness causing less attenuation to acoustic power.POMD04604SEC_WO01 PATENT

[0185] FIG. 13C is a graph of Acoustic Entry Power in watts (W) versus body lumen size in millimeters (mm) corresponding to another example implementation of the two power embodiments. The thicker solid curved line 1322 in FIG. 13C illustrates how the acoustic power may be lower for smaller body lumen diameters than larger lumen diameters within the lower subrange of diameters from about 3.0 mm to about 4.9 mm, and may be lower for smaller body lumen diameters than larger lumen diameters within the upper subrange of diameters from about 5.0 mm to about 8.0 mm. For the graph of FIG. 13C it is assumed that the ultrasound transducer 214 is located within a compliant balloon 108 having nominal balloon diameter (e.g., of 6.5 mm) and a corresponding nominal balloon wall thickness.

[0186] For similar reasons to those described above with reference to FIGS. 12B and 13B, the acoustic power (e.g., in terms of patient entry power at a constant nominal power setting by the controller 104) may be lower for smaller body lumen diameters than larger lumen diameters within the lower subrange of diameters from about 3.0 mm to about 4.9 mm due to one or more folds in the compliant balloon 108, which is / are present when the compliant balloon 108 is partially inflated such that its diameter is less than a nominal balloon diameter (e.g., of 6.5 mm) of the compliant balloon 108, at least partially attenuating some of the first amount of acoustic power emitted by the ultrasound transducer 214. Similarly, the acoustic power (e.g., in terms of patient entry power at a constant nominal power setting by the controller 104) may be lower for smaller body lumen diameters than larger lumen diameters within the upper subrange of diameters from about 5.0 mm to about 8.0 mm due to one or more folds in the compliant balloon 108, which one or more folds is / are present when the compliant balloon 108 is partially inflated such that its diameter is less than a nominal balloon diameter (e.g., of 6.5 mm) of the compliant balloon 108, at least partially attenuating some of the second acoustic power emitted by the ultrasound transducer 214. The dashed line 1330 illustrates for comparison purposes the power curve (e.g., in terms of the nominal power setting by the controller 104) when the attenuation caused by the “folds effect” described above (and further attenuating effects) is not considered. As becomes apparent from a comparison of lines 1322 and 1330, the “folds effect” is more significant for body lumens sizes (and inflated balloon diameters) below the nominal balloon diameter (here: of 6.5 mm), since when the nominal balloon diameter is reached upon inflation of the balloon 108, the folds (e.g., in terms of wrinkles 800) disappear. In practice, it has been found to be advantageous if the nominal balloon diameter is selected greater than thePOMD04604SEC_WO01 PATENT specified intermediate diameter (here: 5 mm) that separates the lower subrange from the upper subrange.

[0187] Fig. 13C also shows a comparison of the two-power strategy discussed above and a more complex six-power strategy using six different catheters. In Fig. 13C, the thin solid line 1324 illustrates the acoustic power (e.g., in terms of acoustic patient power) respectively output by each of the six catheters designed specifically for six particular body lumen sizes and having respective (non-compliant) balloon diameters of 3.5 mm, 4.2 mm, 5.0 mm, 6.0 mm, 7.0 mm, and 8.0 mm inflated to their full sizes. The dotted line 1326 and the dashed line 1328 illustrate the power uncertainties in the acoustic power output for the two- power strategy (line 1322) and the six-power strategy (line 1324), respectively. Those uncertainties are due to inherent system tolerances (e.g., of the excitation source) and other effects. As becomes apparent from the lines 1326, 1328, it has been found that by implementing a slightly tighter tolerance control for the two-power strategy, the resulting (smaller) uncertainties of the two-power strategy can be kept within the power envelope of the six-power strategy, so that consistent clinical outcomes (e.g., in terms of safety and effectiveness) can be ensured.

[0188] As further becomes apparent from the lines 1326, 1328 indicative of the uncertainties of the two-power strategy and the six-power strategy, respectively, the attenuation by the “folds effect” is indeed helpful especially for smaller lumen sizes in the lower and upper subranges to make sure that the acoustic entry power (with its inherent uncertainties) of the two-power strategy does not exceed the power envelope of the (well tested) six-power strategy. If the “folds effect” was not present in the two-power strategy (see line 1330 which illustrates the two-power approach without attenuation by folds), the acoustic power (with its inherent uncertainty, not illustrated in Fig. 13C) would be too high especially in the lower vessel size regions of the lower subrange and the upper subrange (and when assuming that the remaining parameters such as frequency and duration of energy emission remain constant). These findings prove that the two-power strategy indeed is a practical solution (e.g., because consistent lesion depths and, thus, consistent clinical outcomes can be ensured).

[0189] The overall power uncertainty, or tolerance, is defined by two major factors: the power tolerance of the excitation source (also called “generator”) and the uncertainty caused by the catheter acoustic efficiency. Also, the power measurement accuracy may need to be considered. The power tolerance of the excitation source was found to be the largestPOMD04604SEC_WO01 PATENT contributor to the overall power uncertainty. At a low power setting of 10 Watts of a conventional excitation source, the power tolerance can be in the range of + / - 25% and will decrease with higher power settings. At power settings as generally proposed herein of about 25 to 35 Watts, the power tolerance will be in the range of + / - 13%. As such, for the two- power strategy, a power tolerance below + / - 12% and in particular below + / - 10% or below + / - 8% can be implemented. Such a tighter tolerance control becomes possible by, for example, using higher quality components (e.g., in terms of the excitation source) and power control loops. Taking into account the total power uncertainty (including, for example, uncertainty caused by the catheter acoustic efficiency and power measurement uncertainties), a power tolerance below + / - 26% and in particular below + / -21 % or below + / - 16% can be implemented.

[0190] In view of the desired “folds effect,” it can be advantageous not to reduce the tolerances below a certain threshold so that power fluctuations caused by a certain randomness of how and where the folds are arranged and unfold can still be accommodated. Despite an apparent randomness resulting in regard to the folds (e.g., when taking the form of wrinkles), it has been found that there is a predictable, generally linear relationship between the acoustic power attenuation by the folds on the on hand and a “degree of foldedness” on the other hand, with the “foldedness” being mathematically defined as ((nominal balloon diameter / inflated balloon diameter -1) * 100%). When the inflated balloon diameter is greater than the nominal balloon diameter, the “degree of foldedness” is defined to be zero. The acoustic power attenuation can be defined as (1- measured acoustic power / expected acoustic power without folds) * 100%. The expected acoustic power was derived from the mean value of repeated measurements using balloons without folds, whereas the measured acoustic power was measured for similar balloons with folds. It has additionally been found that any remaining randomness in the power distribution caused by the folds is compensated by heat conduction in the tissue. These outcomes provide a consistent physical foundation for the two-power strategy.

[0191] As also becomes apparent from Fig. 13C, in particular the combined contributions of a tight power control and the “folds effect” pave the way for the two-power strategy. The lines 1326, 1328 indicative of the uncertainties of the two-power strategy and the six-power strategy, respectively, further illustrate that it is indeed beneficial to select the nominal balloon diameter (here: 6.5 mm) greater than the specified intermediate diameter (here: 5 mm) that separates the lower subrange from the upper subrange. Such a selectionPOMD04604SEC_WO01 PATENT helps to ensure that the tolerance regime of the two-power strategy remain within the power uncertainty envelope of the six-power strategy.

[0192] In the two-power strategy it is advantageous to select the first amount of acoustic energy based on an acoustic entry power within a first range from about 25.0, 27.5 or 30.0 to about 33.0 watts and to select the second amount of acoustic energy based on an acoustic entry power within a second range from about 32.0 or 33.1 to about 39.0 watts. The duration of the power delivery in the lower subrange can be selected such that the first amount of acoustic energy lies within a range between 140 J to 240 J, or between 165 J and 215 J (e.g., around 190 J). The duration of the power delivery in the higher subrange can be selected such that the second amount of acoustic energy lies within a range between 180 J to 270 J, or between 200 J and 250 J (e.g., around 225 J). In these examples, the generator frequency can be set to around 9 MHz. The energy amounts can be reduced by ca. 15 to 25% in case of a higher frequency of around 12 MHz and increased by ca. 20 to 35% for lower frequencies of around 6 MHz. In all the variants discussed herein, energy measurements can be performed in accordance with IEC 61161 Edition 3.0, 2013-01 or BS EN 62555:2014.

[0193] In accordance with certain embodiments, the controller 104 is configured to automatically determine an estimate of the diameter of the body lumen, e.g., using one of the techniques described in commonly assigned U.S. Patent Application No. 17 / 812,973, titled “Methods And Systems For Determining Body Lumen Size,” filed July 15, 2022, published as US 2023 / 0026504, which is incorporated herein by reference. Additionally, the controller 104 is configured to control the excitation source 1118 to cause the ultrasound transducer 214 to emit the first amount of acoustic energy based on a determination that the estimate of the diameter of the body lumen is within the lower subrange of the specified range of diameters, and control the excitation source 1118 to cause the ultrasound transducer 214 to emit the second amount of acoustic energy based on a determination that the estimate of the diameter of the body lumen is within the upper subrange of the specified range of diameters.

[0194] In accordance with certain embodiments, the user interface 1116 of the system 100 allows a user to specify whether the diameter of the body lumen is within the lower subrange of the specified range of diameters or within the upper subrange of the specified range of diameters. An example of such a user interface 1116 is shown in FIG. 14. In certain embodiments, the user interface 1116 is further configured to display a warning message when an automatically determined estimate of the diameter of the body lumen is not within the subrange input by the user. It is also possible that the user interface 1116 is configured toPOMD04604SEC_WO01 PATENT allow a user to specify the type of body lumen. For example, the controller can store in the memory 1114 a plurality of different types of body lumens and whether each type of body lumen is within the lower subrange of the specified range of diameters or the upper subrange of the specified range of diameters. The plurality of different types of body lumens can include, e.g., a main renal artery, an accessory renal artery, and a renal artery branch, but is not limited thereto. In certain such embodiments, the controller 104 is further configured to control the excitation source 1118 to cause the ultrasound transducer 214 to emit the first amount of acoustic energy when the diameter of the body lumen is specified, using the user interface, to be within the lower subrange of the specified range of diameters, and control the excitation source 1118 to cause the ultrasound transducer 214 to emit the second amount of acoustic energy when the diameter of the body lumen is specified, using the user interface 1116, to be within the upper subrange of the specified range of diameters. The user interface 1116 can also be configured to display a warning message when an automatically determined estimate of the diameter of the body lumen is not within the subrange input by the user.

[0195] FIG. 15 is a high level flow diagram used to summarize a single power method for use with a tissue treatment system having a catheter 102 that includes a distal portion (e.g., a shaft 212) on which is located an ultrasound transducer 214. Referring to FIG. 15, step 1502 involves inserting the distal portion of the catheter 102 into a segment of body lumen having a diameter within a specified range of diameters that is at least 4 mm, such that the ultrasound transducer 214 is located within the segment of the body lumen having the diameter within the specified range of diameters that is at least 4 mm. For example, the range of diameters can be from about 3.0 mm to about 8.0 mm, but is not limited thereto. Further details of such ranges were described above, and thus, need not be repeated. Step 1504 involves causing the ultrasound transducer 214 to emit about a same amount of acoustic energy when the diameter of the segment of the body lumen is within the specified range of diameters that is at least 4mm, e.g., from about 3.0 mm to about 8.0 mm. Example amounts of acoustic energy that could be used in the single power embodiments were described above, and thus, need not be repeated.

[0196] As was explained above, the distal portion of the catheter 102 can include a compliant balloon 108 within which is located the ultrasound transducer 214, wherein the compliant balloon 108 is configured such that when the compliant balloon 108 is partially inflated, such that its diameter is less than a nominal balloon diameter of the compliant balloon, the compliant balloon includes one or more folds, examples of which were describedPOMD04604SEC_WO01 PATENT above. In such certain embodiments, the method can also include causing inflation of the compliant balloon 108 so that the compliant balloon is in apposition with a body lumen wall of the segment of the body lumen within which is located the ultrasound transducer 214. The method can also include utilizing the one or more folds in the compliant balloon to at least partially attenuate some of the acoustic power emitted by the ultrasound transducer 214, and thereby reduce an amount of the acoustic power that passes through the compliant balloon 108 when the diameter of the segment of the body lumen in which the compliant balloon is in apposition is within a smaller diameter subset of the specified range of diameters, compared to when the compliant balloon is inflated such that its diameter is at least the nominal balloon diameter of the compliant balloon and the diameter of the segment of the body lumen in which the compliant balloon is in apposition with is within a larger diameter subset of the specified range of diameters.

[0197] FIG. 16 is a high level flow diagram used to summarize a two power method for use with a tissue treatment system having a catheter 102 that includes a distal portion (e.g., a shaft 212) on which is located an ultrasound transducer 214. Referring to FIG. 16, step 1602 involves inserting the distal portion of the catheter 102 into a segment of body lumen having a diameter within a specified range of diameters that is at least 4 mm, such that the ultrasound transducer is located within the segment of the body lumen having the diameter within the specified range of diameters that is at least 4 mm. For example, the range of diameters can be from about 3.0 mm to about 8.0 mm, but is not limited thereto. Further details of such ranges were described above, and thus, need not be repeated. Step 1604 involves determining whether the diameter of the segment of the body lumen, within which the ultrasound transducer 214 is located, is within a lower subrange of the specified range of diameters or an upper subrange of the specified range of diameters. For example, the lower subrange can be from about 3.0 mm to about 4.9 mm, and the upper subrange can be from about 5.0 mm to about 8.0 mm, but are not limited thereto. For another example, the lower subrange can be from about 3.0 mm to about 4.5 mm, and the upper subrange can be from about 4.6 mm to about 8.0 mm, but are not limited thereto. Further details of such ranges and subranges were described above, and thus, need not be repeated. There is a determination of step 1606, which results in flow going to either step 1608 or 1610. Step 1608 involves causing the ultrasound transducer to emit a first amount of acoustic energy when the diameter of the segment of the body lumen within which the ultrasound transducer 214 is located is determined to be within the lower subrange (e.g., from about 3.0 mm to about 4.9 mm) of thePOMD04604SEC_WO01 PATENT specified range of diameters. By contrast, step 1610 involves causing the ultrasound transducer to emit a second amount of acoustic energy, which is greater than the first amount of acoustic energy, when the diameter of the segment of the body lumen within which the ultrasound transducer is located is determined to be within the upper subrange (e.g., from about 5.mm to about 8.0 mm) of the specified range of diameters.

[0198] In accordance with certain embodiments, the determining at step 1604 (of whether the diameter of the segment of the body lumen, within which the ultrasound transducer is located, is within the lower subrange of the specified range of diameters or the upper subrange of the specified range of diameters) is determined by a user, e.g., using fluoroscopy of some other visualization technique, or the like, and entered by the user into the tissue treatment system using a user interface, e.g., 1116, of the tissue treatment system. An example of such a user interface is shown in FIG. 14, which was discussed above.

[0199] In accordance with certain embodiments, the determining at step 1604 (of whether the diameter of the segment of the body lumen, within which the ultrasound transducer is located, is within the lower subrange of the specified range of diameters or the upper subrange of the specified range of diameters) is determined by accepting an indication, from a user via a user interface, e.g., 1116, of which one of a plurality of different types of body lumens the ultrasound transducer is located. Whether the diameter of the segment of the body lumen (within which the ultrasound transducer is located) is within the lower subrange of the specified range of diameters or the upper subrange of the specified range of diameters, is then determined based on the indication accepted via the user interface. The plurality of different types of body lumens can include, for example, a main renal artery, an accessory renal artery, and a renal artery branch, but are not limited thereto.

[0200] In accordance with certain embodiments, the determining at step 1604 (of whether the diameter of the segment of the body lumen, within which the ultrasound transducer is located, is within the lower subrange of the specified range of diameters or the upper subrange of the specified range of diameters) is automatically determined by the tissue treatment system, e.g., using one of the techniques described in U.S. Patent Application No. 17 / 812,973, titled “Methods And Systems For Determining Body Lumen Size,” filed July 15, 2022, published as US 2023 / 0026504, which is incorporated herein by reference.

[0201] As was explained above, the distal portion of the catheter 102 can include a compliant balloon 108 within which is located the ultrasound transducer 214, wherein the compliant balloon is configured such that when the compliant balloon is partially inflated,POMD04604SEC_WO01 PATENT such that its diameter is less than a nominal balloon diameter of the compliant balloon, the compliant balloon includes one or more folds, examples of which were described above. In such certain embodiments, the method can also include causing inflation of the compliant balloon 108 so that the compliant balloon is in apposition with a body lumen wall of the segment of the body lumen within which is located the ultrasound transducer 214. The method can also include utilizing the one or more folds in the compliant balloon 108 to at least partially attenuate some of the acoustic power emitted by the ultrasound transducer 214, and thereby reduce an amount of the acoustic power that passes through the compliant balloon when the diameter of the segment of the body lumen in which the compliant balloon is in apposition is within a smaller diameter subset of the specified range of diameters, compared to when the compliant balloon is inflated such that its diameter is at least the nominal balloon diameter of the compliant balloon and the diameter of the segment of the body lumen in which the compliant balloon is in apposition with is within a larger diameter subset of the specified range of diameters.

[0202] The body lumen, with which the methods described with reference to FIGS. 15 and 16 may be used, can be a renal artery, but is not limited thereto. For example, the body lumen can be one of: a vein; a pulmonary artery; a vascular lumen; a celiac artery; a common hepatic artery; a proper hepatic artery; a gastroduodenal artery; a hepatic artery; a splenic artery; a gastric artery; superior mesenteric artery; inferior mesenteric artery; portal vein; celiac trunk; pulmonary vein; aorta; vena cava; a blood vessel; a nonvascular lumen; an airway; a sinus; an esophagus; a respiratory lumen; a digestive lumen; a stomach; a duodenum; a jejunum; or a cancer tissue.

[0203] In accordance with certain embodiments, the body lumen into which a catheter of a system described above is inserted into, and used to denervate nerves in tissue surrounding the body lumen, is a renal artery and the nerves comprise renal nerves innervating a kidney. Where a denervation procedure described herein is being performed using a catheter (e.g., 102) inserted into a renal artery type of body lumen, the disease being treated using the denervation procedure can be hypertension or some other disorder associated with elevated sympathetic nerve activity, as can be appreciated from the above discussion. However, it is noted that embodiments of the present technology described herein can alternatively be used in the performance of denervation procedures (and / or other tissue treatment procedures) using catheters that are inserted into other types of body lumens, besides a renal artery, to treat other types of diseases besides hypertension. For example,POMD04604SEC_WO01 PATENT such other types of body lumens include a vein, a pulmonary artery, a vascular lumen, a celiac artery, a common hepatic artery, a proper hepatic artery, a gastroduodenal artery, a hepatic artery, a splenic artery, a gastric artery, a blood vessel, a nonvascular lumen, an airway, a sinus, an esophagus, a respiratory lumen, a digestive lumen, a stomach, a duodenum, a jejunum, a cancer tissue, a tumor, an intestine, and a urological lumen, but are not limited thereto. Examples of other types of diseases that can be treated using certain embodiments of the present technology include pulmonary hypertension, diabetes, obesity, nonalcoholic fatty liver disease, heart failure, end-stage renal disease, digestive disease, cancers, tumors, pain, asthma, or chronic obstructive pulmonary disease (COPD), but are not limited thereto. As has become apparent from the above description, in particular in the context of the two-power strategy as illustrated in Fig. 13C, a tissue treatment system is presented. The system comprises a catheter including a distal portion on which is located an ultrasound transducer, wherein the catheter is configured such that at least the distal portion of the catheter is insertable into a segment of a body lumen having a diameter within a specified range of diameters, wherein the range of diameters has a lower subrange and an upper subrange. The system further comprises an excitation source configured to selectively provide energy to the ultrasound transducer of the catheter and a controller communicatively coupled to the excitation source, the controller configured to control the excitation source to cause the ultrasound transducer to emit two different amounts of acoustic energy, which include a first amount of acoustic energy and a second amount of acoustic energy, which is greater than the first amount of acoustic energy. The controller is configured to control the excitation source to cause the ultrasound transducer to selectively emit the first amount of acoustic energy or the second amount of acoustic energy upon determining that the diameter of a segment of a body lumen to be treated is within the lower subrange or the upper subrange, respectively.

[0204] The controller may be configured to control the excitation source to cause the ultrasound transducer to emit the first amount of acoustic energy upon determining that the diameter of a segment of a body lumen to be treated is within the lower subrange. Similarly, the controller may be configured to control the excitation source to cause the ultrasound transducer to emit the second amount of acoustic energy upon determining that the diameter of a segment of a body lumen to be treated is within the upper subrange. In some variants, the controller is configured to have an operational mode in which only the first amount and the second amount of acoustic energy can selectively be emitted by the excitation sourcePOMD04604SEC_WO01 PATENT under control of the controller, but for example no third amount of acoustic energy different from the first and second amounts of acoustic energy.

[0205] In some variants, only a single type of catheter may be used in such an operational mode. As such, the same catheter may be used in a single procedure to control the excitation source to emit the first amount of acoustic energy in regard to a first segment of a body lumen and the second amount of acoustic energy to a second segment of the same body lumen or another body lumen of the same patient.

[0206] The controller may further be configured to control the excitation source to cause the ultrasound transducer to emit the first amount of acoustic energy when the diameter of the segment of the body lumen is determined by the controller, from at least one of a segment diameter estimate determined automatically by the controller and a user specification via a user interface, to be within the lower subrange of the specified range of diameters. Additionally, or in the alternative, the controller may further be configured to control the excitation source to cause the ultrasound transducer to emit the second amount of acoustic energy when the diameter of the segment of the body lumen is determined by the controller, from at least one of a segment diameter estimate determined automatically by the controller and a user specification via a user interface, to be within the upper subrange of the specified range of diameters. The user interface may be configured to display a warning message when the automatically determined estimate of the diameter of the segment of the body lumen is not within the subrange specified via the user interface.

[0207] The distal portion of the catheter may further include a balloon within which is located the ultrasound transducer. The balloon may be configured to center the ultrasound transducer within the body lumen and to have a fluid circulate through the balloon to cool at least a portion of tissue adjacent to the body lumen within which the ultrasound transducer is positioned.

[0208] The balloon may be or comprise a compliant balloon. The compliant balloon may be configured such that when the compliant balloon is partially inflated, such that its diameter is less than a nominal balloon diameter of the compliant balloon, the compliant balloon includes one or more folds. The one or more folds may be configured to at least partially attenuate some of the acoustic energy emitted by the ultrasound transducer. In some implementations, the folds are configured (e.g., when occurring in a predictable manner) such that when the balloon is inserted into a body lumen segment and partially inflated to less than its nominal balloon diameter, a folded surface of the balloon generates additional acousticPOMD04604SEC_WO01 PATENT reflections compared to when the balloon is inflated to the point that there are no, or less, or smaller folds. The nominal balloon diameter may be within a diameter range of 5.5 mm to 7.5 mm, in particular about 6.5 mm.

[0209] In terms of the acoustic patient entry power (i.e., the power “behind” the balloon as seen from the transducer), the compliant balloon may be configured such that the attenuation caused by the folds leads to the effect that, at a constant nominal power setting by the controller, the acoustic patient entry power may be somewhat lower for smaller body lumen diameters than larger lumen diameters within the lower subrange (e.g., of diameters from about 3.0 mm to about 4.9 mm), and may be somewhat lower for smaller body lumen diameters than larger lumen diameters within the upper subrange of diameters (e.g., from about 5.0 mm to about 8.0 mm). For example, at a nominal power setting selected within a range from around 25 watts to around 35 watts for the lower subrange (e.g., of ca. 30 watts), the attenuation (e.g., in terms of the acoustic patient entry power) may be around 5% to 15% smaller lower for smaller body lumen diameters than larger lumen diameters within the lower subrange. At a nominal power setting selected within a range from around 31 watts to around 41 watts for the upper subrange (e.g., of about 36 watts), the attenuation (e.g., in terms of the acoustic patient entry power) may be around 2% to 10% smaller lower for smaller body lumen diameters than larger lumen diameters within the upper subrange. In this regard, see also lines 1330 and 1322 in Fig. 13C.

[0210] The system may comprise a fluid supply subsystem configured to circulate the fluid through the balloon, and the controller may also be configured to control the fluid supply subsystem. An amount of energy absorbed by tissue surrounding the segment of the body lumen in which the ultrasound transducer is located may depend in part on a flowrate of the fluid circulated through the balloon. In such a case, the controller may be configured to control the flowrate of the fluid circulated through the balloon to be within a flowrate range of about 5 mL / min to about 40 mL / min, in particular about 10 mL / min to about 15 mL / min. The controller may be configured to control the fluid supply system to circulate the fluid through the balloon a predetermined amount of time after the first amount of energy has been emitted by the ultrasound transducer. The predetermined amount of time may be within a range of 2 secs to 12 secs, in particular 5 secs to 9 secs.

[0211] A specified intermediate diameter may separate the lower subrange from the upper subrange. The specified intermediate diameter may comprise one of: about 4.5 mm; about 5.0 mm; or about 5.5 mm. The nominal balloon diameter may be selected to be largerPOMD04604SEC_WO01 PATENT than the specified intermediate diameter. For example, the nominal balloon diameter may be selected to be at least 10%, at least 20% or at least 30 % larger than the specified intermediate diameter.

[0212] A lower end of the specified range of diameters may comprise one of: about 2 mm; about 2.5 mm; or about 3.0 mm. An upper end of the specified range of diameters may comprise one of: about 7.5 mm; about 8.0 mm; or about 8.5 mm.

[0213] The second amount of acoustic energy is at least 8%, at least 10%, at least 12% or at least 15% greater than the first amount of acoustic energy. The first amount of acoustic energy may be based on a first acoustic signal having a first acoustic frequency, a first acoustic power and a first duration. The second amount of acoustic energy may be based on an second acoustic signal having a second acoustic frequency, a second acoustic power and a second duration. The second acoustic power may be greater than the first acoustic power. The second acoustic power may be at least 8%, at least 10%, at least 12%, or at least 15% greater than the first acoustic power. The first acoustic frequency may equal the second acoustic frequency. The first duration may equal the second duration. The first and second acoustic powers may be acoustic patient entry powers indicative of an attenuation caused by folds of a compliant balloon and further attenuation effects. Alternatively, the first and second acoustic powers may be nominal acoustic powers as set by the controller (i.e., not yet considering the balloon-related attenuation). A total tolerance range for generating the first and second acoustic powers may be below 15%, below 11% or below 8%.

[0214] The range of diameters is at least 4 mm. The controller may be configured to control the excitation source to cause the ultrasound transducer to emit only the two different amounts of acoustic energy.

[0215] The first amount of acoustic energy may be based on a first acoustic power within a first range from about 27.5 or 30.0 to about 33.0 watts. The second amount of acoustic energy may be based on a second acoustic power within a second range from about 33.1 to about 39.0 watts. For example, the first amount of acoustic energy is based on a first acoustic power within a first range from about 29.0 or 31.0 to about 33.0 watts and the second amount of acoustic energy is based on a second acoustic power within a second range from about 33.1 to about 38.0 watts. In particular, the first amount of acoustic energy may be based on a first acoustic power of about 30.1 or 32.0 watts and the second amount of acoustic energy is based on a second acoustic power of about 36.0 watts (e.g., 35.8 watts). The first and second acoustic powers may be one of acoustic patient entry powers and nominalPOMD04604SEC_WO01 PATENT acoustic power as set by the controller. See also the illustration in the diagram of Fig. 13C, see line 1330.

[0216] Also presented is a method of operating a tissue treatment system, the system comprising a catheter including a distal portion on which is located an ultrasound transducer, wherein the catheter is configured such that at least the distal portion of the catheter is insertable into a segment of a body lumen having a diameter within a specified range of diameters, wherein the range of diameters has a lower subrange and an upper subrange; an excitation source configured to selectively provide energy to the ultrasound transducer of the catheter; and a controller communicatively coupled to the excitation source, the controller configured to control the excitation source to cause the ultrasound transducer to emit two different amounts of acoustic energy, which include a first amount of acoustic energy and a second amount of acoustic energy, which is greater than the first amount of acoustic energy; wherein the method comprises the following steps performed by the controller: determining if a diameter of a segment of a body lumen to be treated is within the lower subrange or the upper subrange; and controlling the excitation source to cause the ultrasound transducer to selectively emit the first amount of acoustic energy if the diameter of the segment of a body lumen to be treated is determined to be within the lower subrange, or to emit the second amount of acoustic energy if the diameter of the segment of the body lumen to be treated is determined to be within the upper subrange. This method may be carried out by any of the two-power systems described herein.

[0217] FIG. 17 is a flowchart of a method of inflating a balloon, in accordance with certain embodiments. The tissue treatment system 100 can perform the method to conditionally control a speed of the fluid supply actuator 1056. More particularly, the tissue treatment system 100 can conditionally control the fluid supply subsystem 1130 to stabilize balloon pressure in an inflated state. Control of the fluid supply subsystem 1130 and stabilization of the balloon pressure may be based on a monitored pressure of the balloon during the inflation process. The conditional control of balloon pressure is based on supply line pressure and corresponding actuator speeds, as shown in FIGS. 18-19. Accordingly, FIGS. 17-19 are described in combination below.

[0218] Referring to FIG. 18 A, a graph of fluid pressure of a tissue treatment system versus time is shown in accordance with certain embodiments. Referring to FIG. 18B, a graph of fluid flow of a tissue treatment system versus time is shown in accordance with certain embodiments. At operation 1702a, the fluid pressure 1800 of a fluid in the supply linePOMD04604SEC_WO01 PATENT1050 is monitored. The fluid pressure 1800 can be monitored by the supply pressure sensor 1060. More particularly, the supply pressure sensor 1060 can detect the fluid pressure 1800 and generate a signal that is monitored by the processing device 1112. The processing device 1112 may, in response to the fluid pressure signal, determine or generate drive signals to control a speed of the fluid supply actuator 1056. More particularly, the processing device 1112 can utilize software to conditionally control the irrigation motor speed during inflation, in conjunction with sensed supply pressure.

[0219] Monitored pressure values may be based on both supply pressure sensor 1060 and return pressure sensor 1066 readings. For example, the pressure value may be based on a difference between the readings. In certain embodiments, the sensed pressure value on which control determinations is a value between a pressure value of the supply line 1050 as sensed by the supply pressure sensor 1060 and a pressure value of the return line 1064 as sensed by the return pressure sensor 1066. For example, when the pressure in the supply line 1050 is 2 psi and the pressure in the return line 1064 is -10 psi, the pressure value may be determined to be -4 psi. Accordingly, the processing device 1112 can generate or send drive signals based on intermediate pressure values between the supply and return pressures.

[0220] The fluid supply actuator 1056, e.g., irrigation motor, may be started at a beginning of the inflation process. When the inflation process begins, the processing device 1112 can send a drive signal to the fluid supply subsystem to cause the fluid supply actuator 1056 to deliver fluid at a flow rate. In certain embodiments, at operation 1704a, in response to the monitored fluid pressure 1800 being below a first pressure value 1802 (FIG. 18 A), the processing device 1112 can send a first drive signal to cause the fluid supply actuator 1056 to deliver fluid at a first flow rate 1804 (FIG. 18B).

[0221] In the initial stage of the inflation process, the fluid supply subsystem can inflate the balloon more aggressively than later stages during which the balloon pressure is stabilized. By using a more aggressive, i.e., higher, flow rate initially, the time to get a balloon, e.g., a compliant balloon, to a stabilized pressure is minimized without overshooting the target balloon working pressure, thereby improving safety of the device. In certain embodiments, the catheter inlet valve V2 can be left open to avoid a balloon pressure spike and reach a stabilized balloon pressure faster. In certain embodiments, the flow rate is higher in the initial stage than in later stages, for example between 25 mE / min and 35 mE / min in the initial stage and between 10 mL / min and 20 mL / min in a later stage and between 2 mL / min and 8 mL / min in a still later stage. Inflating the balloon more aggressively at an initial stagePOMD04604SEC_WO01 PATENT reduces the time needed to inflate the balloon. For example, the inflation process until a predetermined, e.g., user intended, balloon pressure is achieved may be performed in a total inflation time of 15 seconds or less, preferably in a total inflation time of 10 seconds or less, and more preferably in a total inflation time of 5 seconds or less. A shortened inflation time reduces surgery time and thus health risk for the patient.

[0222] In some variants, at operation 1702b, a processing device 1112 determines that a first balloon pressure is below a first balloon pressure threshold, e.g., below -2 psi, and, at operation 1704b, sends a first drive signal to cause the fluid actuator to use a motor speed at a first flow rate, e.g., 30 mL / min. At operation 1706b, the processing device 1112 subsequently determines that a second balloon pressure is below a second balloon threshold, the second balloon threshold being above the first balloon pressure threshold, e.g., below 3 psi, and sends a second drive signal to cause the fluid actuator to use a motor speed at a second flow rate, the second flow rate being below the first flow rate, e.g., between 10 mL / min and 20 mL / min, e.g., 15 mL / min. At operation 1708b, the processing device 1112 subsequently monitors the balloon pressure for a period of time, e.g., 2 seconds, and at operation 1708b, determines that a third balloon pressure is below a third balloon threshold, the third balloon threshold being above the second balloon pressure threshold, e.g., below 10 psi, e.g. below 9.9 psi, e.g., below 8 psi. e.g., below 7 psi, and, at operation 1710b, sends a third drive signal to cause the fluid actuator to use a motor speed at a third flow rate, the third flow rate being below the second flow rate, e.g., between 2 mL / min and 8 mL / min, e.g., 5 mL / min may be used. By implementing this method, balloon pressure may be quickly, e.g., in 15 seconds or less, stabilized at a target pressure, e.g., 10 psi, without exceeding the target pressure. In certain embodiments, a compliant balloon is inflated to a target pressure suitable for cooling non-target tissue before, during, and / or after treatment in 15 seconds or less, e.g., 10 seconds, e.g., 5 seconds, without exceeding the target pressure.

[0223] For example, the first pressure value 1802 may be 0 psi (gauge pressure) and the first flow rate 1804 can be 30 mL / min. The first pressure value 1802 may depend on an access anatomy. In certain embodiments, when the tissue treatment system 100 is delivered into a patient through a femoral location, the first pressure value 1802 may be 0 psi. By contrast, when the tissue treatment system 100 is delivered into the patient at a radial location, the first pressure value 1802 may be -1 psi. In any case, the first flow rate 1804 can be relatively high, and can cause the balloon to quickly inflate to a positive (above atmospheric) pressure.POMD04604SEC_WO01 PATENT

[0224] The fluid pressure 1800 can be continuously monitored to allow the flow rate to be adjusted when the first pressure value is met. At operation 1706a, in response to the fluid pressure 1800 being above the first pressure value 1802 and below a second pressure value 1806 (FIG. 18 A) a second drive signal is sent by the processing device 1112 to cause the fluid supply actuator 1056 to deliver fluid at a second flow rate 1808 (FIG. 18B). The first pressure value 1802 can be lower than the second pressure value 1806. For example, the second pressure value 1806 may be 5 psi, as compared to the first pressure value of 0 psi. Furthermore, the second flow rate 1808 can be lower than the first flow rate 1804. For example, the second flow rate 1808 can be 15 mE / min, as compared to the first flow rate 1804 of 30 mE / min.

[0225] The second pressure value 1806 may depend on an access anatomy. In certain embodiments, when the tissue treatment system 100 is delivered into a patient through a femoral location, the second pressure value 1806 may be 5 psi. By contrast, when the tissue treatment system 100 is delivered into the patient at a radial location, the second pressure value 1806 may be 4 psi. In any case, the lower second flow rate 1808 can cause the balloon to expand moderately (less aggressively) toward an intended inflation diameter and pressure at a lower rate. Nonetheless, the second flow rate 1808 can still cause the balloon to reach an intended final pressure quickly.

[0226] When the second pressure value 1806 is reached, the controller 104 can adjust inflation to begin to stabilize the balloon pressure. At operation 1708a, in response to the fluid pressure 1800 being above the second pressure value 1806 (FIG. 18 A) a third drive signal is sent by the processing device 1112 to cause the fluid supply actuator 1056 to deliver fluid at a third flow rate 1810 (FIG. 18B). The third flow rate 1810 can be lower than the second flow rate 1808. For example, the third flow rate 1810 can be 5 mL / min, as compared to the second flow rate 1808 of 15 mL / min. The lower flow rate can allow the balloon to continue to expand, however, rather than the expansion being predominantly driven by fluid delivery, a considerable amount of the expansion can come from the balloon compliance. More particularly, the balloon can stretch from internal material stresses, in addition to the increasing fluid volume, to cause the balloon to expand toward a state of equilibrium at a final inflation pressure.

[0227] When the intended final inflation pressure is reached, the fluid delivery can be discontinued or reduced. The target inflation pressure can be a third pressure value 1812 (FIG. 18A). The third pressure value 1812 may be higher than the second pressure valuePOMD04604SEC_WO01 PATENT1806. For example, the third pressure value 1812 can have a target value of 10.1 psi, as compared to the second pressure value 1806 of 4 or 5 psi (depending on access anatomy). When the supply pressure reaches the third pressure value 1812, the processing device 1112 can send a third drive signal to cause the fluid supply actuator 1056 to reduce fluid delivery. For example, the flow rate of the fluid supply actuator 1056, after the balloon pressure reaches the third pressure value 1812, can be reduced to zero. The compliant balloon may continue to expand within a desired pressure range, e.g., 9-11 psi, and the desired inflated size and shape.

[0228] After reaching the intended final balloon pressure, the system can monitor and adjust fluid delivery as needed to maintain the inflated state. In certain embodiments, at operation 1710a, the processing device 1112 can send a fourth drive signal in response to the fluid pressure 1800 being below a threshold value after being above the third pressure value 1812 (FIG. 18A). The fourth drive signal can cause the fluid supply actuator 1056 to deliver fluid at a fourth flow rate 1816 (FIG. 18B). The third pressure value 1812 can be higher than the threshold pressure value 1814. For example, the third pressure value 1812 can be 10.1 psi and the threshold pressure value 1814 can be 9.6 psi. Accordingly, when the balloon pressure begins to drop, e.g., as a result of balloon distension caused by compliance of the balloon, the fluid supply subsystem can restart fluid delivery to raise the balloon pressure to the intended final pressure value. The fourth flow rate 1816 may be a relatively low rate, e.g., 5 mE / min. The balloon may therefore gradually return to the intended final balloon pressure, e.g., 10.1 psi, at which point a speed of the irrigation motor can again be reduced or stopped. The conditional control of the irrigation motor can therefore stabilize the balloon pressure and maintain the balloon pressure at or near the intended final balloon pressure at which the balloon has an intended size and shape. Accordingly, the balloon pressure can remain within specifications.

[0229] The fourth flow rate 1816 may be selected to ensure that the balloon pressure does not increase when there is a leak in the system. For example, the fourth flow rate 1816, e.g., 5 mE / min, may be insufficient to replace leaking inflation fluid. The balloon may therefore continue to drop in pressure when the drop to the threshold pressure value 1814 is caused by a system leak, rather than inherent balloon compliance. Accordingly, leaks can be detected and the fluid supply subsystem can, in response to such detection, halt operation to allow system troubleshooting to take place.POMD04604SEC_WO01 PATENT

[0230] Referring to FIG. 19, a graph of balloon pressure of a tissue treatment system versus time is shown in accordance with certain embodiments. The control algorithm described above can stabilize the final inflation pressure of the balloon, regardless of a target anatomy size. More particularly, the balloon can be expanded into blood vessels of different sizes, e.g., small artery or large artery, and body lumens of different sizes, with a single size balloon or minimal number of differently sized balloons. In fact, as illustrated, the balloon may be expanded into free space (open and unconstrained) and still stabilize the balloon pressure at the target pressure. In any case, the balloon will be controlled to quickly reach a target pressure, while allowing the balloon to thereafter be gradually adjusted to compensate for any inherent expansion of the balloon due to material compliance. The path to the final pressure may vary depending on whether the balloon expands into a structure, e.g., a tube, however, the balloon pressure can still stabilize in approximately the same amount of time. Accordingly, the control methodology can allow the balloon to be inflated into different vessels and still reliably stabilize the balloon pressure.

[0231] The pressure stabilization may be enabled by the system components. As described above, the fluid supply actuator 1056 can include a motor, and the motor may be operated at various motor speeds to produce the referenced flow rates. More particularly, the first drive signal, the second drive signal, and the third drive signal can cause the motor to operate at respective motor speeds.

[0232] During motor operation, e.g., actuation of the fluid supply actuator 1056, system components may operate to reduce a likelihood of abrupt pressure value excursions. In certain embodiments, the supply valve 1052 is fully open when the fluid supply actuator 1056 is delivering fluid. Keeping the supply valve 1052 fully open can have several advantages. First, the flow rate can be controlled by the motor speed, rather than by the valve orifice size. Accordingly, the flow rate can be directly controlled by adjusting the fluid supply actuator 1056. Second, the open valve can avoid balloon pressure spikes. The fully open orifice can reduce a likelihood of abrupt pressure changes that accompany valve actuation. Accordingly, the valve operation can contribute to stabilized balloon pressures during the inflation process and when the balloon is in the inflated state.

[0233] In some variants, regulating the fluid flow rate may comprise sending, in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate; sending, in response to the fluid pressure being above the first pressure value and below a second pressure value, a secondPOMD04604SEC_WO01 PATENT drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate; and sending, in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

[0234] In some variants, the tissue treatment system may comprise a compliant balloon that is to be inflated, wherein the compliant balloon may be configured to stretch from internal material stresses, in addition to an increasing fluid volume. The processing device may then be configured to regulate the fluid flow rate to achieve a fluid pressure that stabilizes a pressure of the balloon at a predetermined pressure. For example, a flow rate may be regulated to achieve a fluid pressure at which the balloon no longer inflates or deflates, i.e. at which the balloon pressure is held generally constant. In detail, the flow rate may be regulated to achieve the predetermined balloon pressure relatively fast due to the aggressive flow rate at the initial stage. When the predetermined pressure is reached, the balloon may stretch due to material stresses and the flow rate has to be raised over time to compensate for the stretching until the balloon no longer stretches from material stresses at the predetermined balloon pressure. A compliant balloon has the advantage that it can be used for various use cases, i.e., within various vessels (e.g., of different diameters) or in different locations within the same vessel having different diameters. The stabilized pressure may be predetermined by a user. The stabilized pressure may be between 9 psi and 11 psi, preferably between 9.5 psi and 10.5 psi, more preferably at 10 psi. The stabilized pressure may be maintained for at least 2 minutes.

[0235] In some variants, the method may comprise sending, by the processing device in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate. The method includes sending, by the processing device in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate. The method includes sending, by the processing device in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

[0236] In some variants, the fluid supply subsystem may comprise a compliant balloon that is to be inflated, wherein the compliant balloon may be configured to stretch from internal material stresses, in addition to an increasing fluid volume. The flow rate may then be regulated to achieve a fluid pressure that stabilizes a pressure of the balloon at a predetermined pressure. In other words, the flow rate may be adapted, e.g., raised over time,POMD04604SEC_WO01 PATENT to compensate for the stretching of the compliant balloon at a predetermined balloon pressure until the balloon no longer stretches from material stresses at the predetermined balloon pressure

[0237] In some variants, regulating the fluid flow rate may comprise sending, by the processing device in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate, sending, by the processing device in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate, and sending, by the processing device in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

[0238] FIG. 20 is a flowchart of a method of deflating a balloon, in accordance with certain embodiments. The tissue treatment system 100 can perform the method to conditionally control a speed of a return motor. More particularly, the tissue treatment system 100 can conditionally control the fluid supply subsystem to prevent collapse of a catheter lumen balloon deflation. Control of the fluid supply subsystem and regulation of the catheter lumen opening may be based on a monitored pressure of a catheter outlet during the deflation process. The conditional control is represented by catheter outlet pressure and corresponding actuator speeds, as shown in FIGS. 21-22. Accordingly, FIGS. 20-22 are described in combination below.

[0239] Referring to FIG. 21 A, a graph of fluid pressure of a tissue treatment system versus time is shown in accordance with certain embodiments. Referring to FIG. 21B, a graph of fluid flow of a tissue treatment system versus time is shown in accordance with certain embodiments. At operation 2002, the fluid pressure 1800 of a fluid in the return line 1064 is monitored. The return line 1064 fluid pressure 1800 can be monitored by the return pressure sensor 1066. More particularly, the return pressure sensor 1066 can detect the fluid pressure 1800 and generate a signal that is monitored by the processing device 1112. The processing device 1112 may, in response to the fluid pressure signal, determine or generate drive signals to control a speed of the fluid return actuator 1062. More particularly, the processing device 1112 can utilize software to conditionally control the return motor speed during deflation, in conjunction with sensed balloon pressure.POMD04604SEC_WO01 PATENT

[0240] When sonication is complete, the tissue treatment system 100 may enter a deflation process to deflate the balloon such that the catheter 102 may be removed from the patient. The fluid return actuator 1062 may be started at a beginning of the deflation process. When the deflation process begins, the processing device 1112 can send a drive signal to the fluid supply subsystem to cause the fluid return actuator 1062 to remove fluid at a flow rate. In certain embodiments, at operation 2004, in response to the monitored fluid pressure 1800 being above (more than) a first vacuum value 2102 (FIG. 21 A), the processing device 1112 can send a first drive signal to cause the fluid return actuator 1062 to remove fluid from the catheter 102 at a first flow rate 2104 (FIG. 2 IB).

[0241] The first flow rate 2104 can have a value to cause rapid deflation of the balloon. For example, at the first flow rate 2104, the balloon pressure can rapidly decrease from the target inflation pressure. As the balloon deflates, the return line 1064 pressure can decrease, e.g., from 10.1 psi to -10 psi. The deflation time to reach such a level may be only a few seconds, e.g., less than 3 seconds.

[0242] It has been shown that sustained low pressures in the return line 1064 can result in collapse of the catheter shaft. For example, testing confirmed that sustained return line pressures of -12 psi can cause the catheter shaft lumen to at least partially collapse, resulting in a long duration of the deflation process. The deflation process was shown to last more than 10 seconds. Fong deflation times can prolong procedures. Accordingly, the control methodology may aim to maintain flow rates at a level that return line pressures will remain at or around -10 psi, resulting in reduced deflation times.

[0243] At operation 2006, in response to the fluid pressure 1800 being below (less than) the first vacuum value 2102 and above a second vacuum value 2106 (FIG. 21 A), a second drive signal can be sent by the processing device 1112 to cause the fluid return actuator 1062 to remove fluid from the catheter 102 at a second flow rate 2108 (FIG. 21B). The first vacuum value 2102 may be higher than the second vacuum value 2106. For example, the first vacuum value 2102 can be -10 psi and the second vacuum value 2106 may be -12 psi. When the sensed pressure is within that range, the second flow rate 2108 can be set at a lower value than the first flow rate 2104. For example, the second flow rate 2108 can be 5 mE / min and the first flow rate 2104 can be 25 mL / min. As a result, the return line 2108 vacuum value can be maintained in a range of -10 psi to -12 psi.

[0244] At operation 2008, the processing device 1112 can stop the fluid return actuator 1062. For example, when the return line pressure is sensed to be below a level atPOMD04604SEC_WO01 PATENT which lumen collapse occurs, e.g., -12 psi, the fluid flow and deflation can be stopped. More particularly, the fluid return actuator 1062 can be stopped in response to the fluid pressure 1800 being below the second vacuum value 2106. As a result, the return line pressure value can be allowed to increase slightly as the catheter shaft lumen opens and the fluid within the return line 1064 and the balloon equalizes.

[0245] When the return line 1064 pressure is again between the first vacuum value 2102 and the second vacuum value 2106, e.g., between -10 psi to -12 psi, removal of fluid can be resumed to continue balloon deflation. The system can cycle between the first flow rate 2104 and the second flow rate 2108 until the target balloon pressure is reached. When the target balloon pressure is reached, the process can be stopped and the catheter 102 can be removed from the patient. It will be appreciated, accordingly, that actuator control may alternatively be based on pressure readings taken for the balloon pressure (instead of or in addition to the return line 1064 pressure readings).

[0246] Referring to FIG. 22, a graph of balloon pressure of a tissue treatment system versus time is shown in accordance with certain embodiments. The process of rapidly removing fluid from the balloon and then maintaining a steady vacuum state that does not cause catheter shaft collapse can substantially reduce deflation times. For example, deflation of the balloon has been shown to occur in about 5 seconds when the return line pressure is maintained between -10 psi and -12 psi, which compares favorably to the more than 10 seconds that may be required to deflate the balloon when return line vacuum values of less than -12 psi are used.

[0247] Referring to FIG. 23, a graph of power output of an ultrasound transducer versus time is shown in accordance with certain embodiments. As described above, the excitation source 1118 can provide energy to the ultrasound transducer 214 to drive treatment. The ultrasound transducer 214 can ramp up to a target steady state power, e.g., 40 W, according to a power output model 2302. The power output model 2302 may be an idealized power output of the transducer over time. For example, the power output model 2302 can include an exponential relationship between the power output of the transducer and time. More particularly, the power output can begin at zero when energy delivery to the transducer is initiated, and the power output can asymptotically approach the target steady state power as time increases. An equation defining the exponential decay function driving power output toward the steady state power can be: P(t) = Pss* (1 - e1 45t), where P(t) is an instantaneous power at a given time, Pssis the target steady state power, e.g., 40 W, and t isPOMD04604SEC_WO01 PATENT the given time. Based on such idealized power output, sonication will have a low power output at time zero, and rapidly increase toward the steady state power. For example, the power output can reach 90% of the target steady state power within 2 seconds, e.g., 1.6 seconds, and then asymptotically approach the steady state power over a remainder of time until sonication is stopped.

[0248] The power output model 2302 is idealized and actual power output of the transducer can deviate from the target model based on real-world conditions, e.g., control methodology, electronic specifications, etc. Accordingly, an actual power output curve 2304 may approximate the power output model 2302, however, a power accuracy can vary over time. Power accuracy, which may be defined as a ratio of actual power output to target power output, can spike or drift from the ideal curve, particularly as the derivative of the power curve decreases, e.g., a slope shifts from a steep to a flat profile (along a knee of the curve). As illustrated in FIG. 23, when conventional PI or PID control methodologies are used to adjust output of the excitation source 1118 to correspondingly adjust output of the transducer, the actual power output can spike and oscillate as the power output is brought back to the idealized curve. This deviation from the idealized exponential decay function can be reduced by a control methodology based on DAC count models, as described below.

[0249] Referring to FIG. 24, a schematic of a power controller of a tissue treatment system is shown in accordance with certain embodiments. The controller 104 can implement a control methodology that receives the return electrical signal 1190 as an input and determines a DAC count as an output. As described above, by adjusting the DAC count of the excitation source 1118, the controller 104 dynamically adjusts the output energy supplied to the transducer, which in turn adjusts the power output from the transducer to the target tissue. Therefore, accurately controlling the DAC count can produce actual power output from the transducer that stably and smoothly follows the power output model 2302 between zero and the target steady state power output.

[0250] In certain embodiments, the controller 104 includes a low-pass filter 2404 through which the return electrical signal 1190 passes. The low-pass filter 2404 can be applied to the return electrical signal 1190. The return electrical signal 1190 corresponds to an actual power output of the transducer. More particularly, a physical correspondence exists between the power output by the bi-directional coupler 1136 and the power output by the transducer, e.g., based on electrical performance of the output transformer 1138, output filter 1140, etc. The relationship can be known and accounted for by the controller 104 and, thus,POMD04604SEC_WO01 PATENT measuring the return electrical signal 1190 can be used to determine the transducer power output.

[0251] The effect of applying the low-pass filter 2404 is described further below, and effectively reduces noise in the measured return electrical signal 1190 that then translates to reduced noise in the DAC count definition and transducer power output. The low-pass filter 2404 can be implemented in software instructions stored by the memory 1114 of the controller 104. Alternatively, the low-pass filter 2404 may include hardware components. In any case, the low-pass filter 2404 may, from a process flow standpoint, be located between the bi-directional coupler 1136 and the ADC(s) 1152, 1154.

[0252] The ADC(s) 1152, 1154 can receive the filtered return electrical signal 1190 and convert the analog signal to a digital signal. The digital signal may then be passed to a comparator 2406 of the controller 104 to compare the actual (as measured or estimated) output power of the transducer to the target output power. The comparison can be used by, e.g., a difference value may be determined and input to, a feedback control module 2408 of the controller 104 to determine a next DAC count. For example, when the previous DAC count resulted in an actual power output that is lower than the target power output, the DAC count can be adjusted to increase power output, and vice versa. The controller 104 and control methodology is described in further detail below.

[0253] Referring to FIG. 25, a flowchart of a method of controlling power output of an ultrasound transducer by a controller of a tissue treatment system is shown in accordance with certain embodiments. The control method includes operations that are illustrated in FIGS. 26-32. Accordingly, FIGS. 25-32 are described in combination below.

[0254] Referring to FIG. 26, a graph of DAC count of an excitation source versus power output of a first ultrasound transducer is shown in accordance with certain embodiments. At operation 2502, the memory 1114 of the controller 104 stores DAC count models relating DAC count of the excitation source 1118 to power output of the ultrasound transducer 214. DAC count models may be mathematical models defining a relationship between the DAC count and the power output. The models may be represented graphically, as in FIG. 26, or may be stored algorithmically, e.g., as a mathematical function equation, or otherwise. For example, the DAC count models may be stored as a data structure, e.g., a lookup table, in which an input power value is mapped to a corresponding output DAC count.

[0255] The DAC count models can be empirically derived models. An example of empirical data used to derive a DAC count model that is stored in the memory 1114 is shownPOMD04604SEC_WO01 PATENT in FIG. 26. The data can include measurements of output power of a test transducer when driven by a DAC count by a first test excitation source. A power output 2602 may be measured and the corresponding DAC count 2604 recorded over a range of values that encompass the power output model 2302 range, e.g., 0 to 85 W. Accordingly, the range of measured values is expected to cover the range of output values of the transducer during the sonication.

[0256] The empirical data for the first test excitation source and first test transducer combination can cover various frequencies. More particularly, the transducer can be driven at different frequencies to simulate different operating conditions. At a first frequency 2606, e.g., 8.5 MHz, the DAC count 2604 can be higher than a DAC count 2604 for a same output power when the transducer is driven at a second frequency 2608. Similarly, the DAC count 2604 can be lower at a third frequency 2610. The empirical data can provide a representation of system behavior for a particular excitation source operation and transducer impedance.

[0257] Referring to FIG. 27, a graph of DAC count of an excitation source versus power output of a second ultrasound transducer is shown in accordance with certain embodiments. Additional sets of empirical data can be generated to represent the operation of additional excitation source(s) 1118 and / or transducer(s). In certain embodiments, data can include measurements of output power of a second test transducer when driven by a DAC count by a second test excitation source 1118. The empirical data can provide a representation of system behavior for a particular excitation source operation, e.g., at the first frequency 2606, the second frequency 2608, and the third frequency 2610, and transducer impedance.

[0258] The empirical data representing measured RF power versus DAC counts 2604 for voltage can be produced for several excitation source and transducer combinations. For example, ten or more, e.g., thirteen, excitation sources 1118 may be used to drive five or more, e.g., nine, different transducers, at a range of frequencies, e.g., 8.5 MHz, 9.0 MHz, and 9.5 MHz. Additional measured data has been generated and confirms the relationship between DAC count 2604 and measured RF power output 2602 shown in FIGS. 26-27. More particularly, the relationship between measured RF power and DAC count is not random and, rather, follows a continuous and repeatable pattern that can therefore be modeled.

[0259] Referring to FIG. 28, a graph of a first DAC count model relating DAC count of an excitation source to power output of an ultrasound transducer is shown in accordance with certain embodiments. Modeling of the relationship between DAC count of thePOMD04604SEC_WO01 PATENT excitation source 1118 and output transducer power can be achieved by consolidating data for the tested excitation sources. For example, the empirical data at a given operational frequency, e.g., 9.0 MHz, and a single transducer, e.g., one having a 50 ohm load equivalent at the operational frequency, can be charted for the ten or more excitation sources 1118. The resulting data points are shown in the graph, and it will be readily appreciated that the data points overlap to form the shape of a nonlinear curve. More particularly, the relationship between DAC count 2604 and measured power is nonlinear.

[0260] In certain embodiments, a mathematical model curve-fits the nonlinear relationship between DAC counts 2604 for voltage and output power. More particularly, a mathematical method can be used to find a best- fitting curve to the data points to generate a DAC count model 2802. The DAC count model 2802 can include the best fit curve. For example, least squares curve fitting may be used to minimize a sum of the squares of residuals of the data point from the DAC count model curve 2802. Accordingly, the DAC count model 2802 can be a nonlinear model based on nonlinear least squares.

[0261] In certain embodiments, the DAC count model 2802 can include a specific equation defining the model curve, and therefore defining the relationship between DAC counts 2604 and output transducer power. The equation may have the form: NDAC = k * [sqrt(P0Ut + Ci) + C2], where NDAC is a number of DAC counts 2604, k is a coefficient specific to the DAC count model being defined, Pout is an output power of the transducer, and both Cl and C2 are constants. By way of example, a particular form of the equation defining the DAC count model 2802 shown in FIG. 22 can be NDAC = (-1.80 x 102) * [sqrt(P0Ut + (1.22 x 10"6)) + (4.10 x 103)] . Accordingly, a base model for driving a particular equivalent load can be defined in the nonlinear model.

[0262] Referring to FIG. 29, a graph of several DAC count models relating DAC count of an excitation source to power output of an ultrasound transducer is shown in accordance with certain embodiments. Each of the DAC count models 2802 can be derived from corresponding empirical data, as described above with respect to FIGS. 26-27. For example, the DAC count models can include a first DAC count model 2902, which may be the base model illustrated in FIG. 28, for example. The DAC count models 2802 can include additional models that are offset from the base model. For example, a second DAC count model 2904 can be offset above the base model. Whereas the first DAC count model 2902 can represent the empirical data at a given operational frequency, e.g., 9.0 MHz, and a single transducer, e.g., one having a 50 ohm load equivalent at the operational frequency, the secondPOMD04604SEC_WO01 PATENT base model 2904 may represent the same transducer at a different operational frequency, or a different adjustment in the system parameters. Accordingly, the differences in the curves may represent shifts that occur due to variations between systems or conditions.

[0263] From a mathematical standpoint, the DAC count models 2802 can have similar equations describing the best-fit curves that the models represent. For example, the curves may be represented by the general equation described above, with the only difference between the curves being the coefficient, k. Accordingly, DAC count models 2802 above the base model can have higher values of the coefficient, k, and DAC count models 2802 below the base model can have lower values of the coefficient, k. The range of coefficient values would depend on the empirical data and, as an example only, could be between -122 and - 320.

[0264] Referring to FIG. 30, a graph illustrating a difference between an actual power output of an ultrasound transducer and a target power output of the ultrasound transducer 214 is shown in accordance with certain embodiments. The DAC count models 2802 stored in the memory 1114 of the controller 104 can be referenced by the controller 104 when performing the DAC count control. At operation 2504, the processing device 1112 can send a first DAC count related to a target power output of the ultrasound transducer 214 by a first DAC count model of the DAC count models 2802. The first DAC count model 2902 may, for example, be the base model described above. The controller 104 can reference the first DAC count model 2902 based on the target power output, which is known from the power output model 2302. For example, at time 0.4 seconds the power output model 2302 may define the target power output to be 37% of the steady state power output, e.g., 15 W for a 40 W steady state target. The controller 104 may therefore input 15 W as Pout in the governing equation and, using the coefficient, k, which is unique to the first DAC count model, determine the first DAC count value.

[0265] The controller 104 can send the first DAC count 3002 value to the excitation source 1118, e.g., the DAC 1142, to cause the excitation source 1118 to drive the transducer. After a first iteration of the control algorithm, the return electrical signal 1190 can be returned from the excitation source 1118 to the controller 104 for evaluation. The return electrical signal 1190 can be passed through the low-pass filter 2404 in order to remove internal noise of the excitation source 1118. Each iteration can have a time interval of 5 to 50 ms and, thus, the return electrical signal 1190 can be measured by the controller 104 continuously or in discrete time windows over the time interval. For example, the return electrical signal 1190POMD04604SEC_WO01 PATENT may be sampled every 5 ms, and the average of 10 samples over a 50 ms time interval may be used as the return electrical signal 1190 value.

[0266] At operation 2506, the processing device 1112 determines a difference 3006 between an actual power output 3008 of the ultrasound transducer 214 and the target power output 3004. For example, the return electrical signal 1190 to which the low-pass filter 2404 was applied can be digitized to determine the actual power output 3008, and the digitized value can be compared to the target power output 3004 value, e.g., 15 W in the above example. In the event that the actual power output 3008 value is 20 W, the difference 3006 or error may be calculated as: Error = 1 - (Pactuai / Ptar et) = 1 - (20 / 15) = -0.33. Accordingly, after the generated voltage has been converted into power for transmission to an energy emitter, the feedback controller 104 calculates an error between measured power and the ideal, planned-for power.

[0267] The difference 3006 between the actual and target values can be used in the control methodology as an error that the system attempts to reduce to a minimum value, e.g., zero. The method of reducing the difference 3006 can include implementing a second DAC count model 2904 that more accurately describes system operation and, thus, allows for determination of a second DAC count 3012 to drive the transducer to the next target power output 3004. More particularly, the error value can determine which DAC count model 2802 to use.

[0268] In certain embodiments, the processing device 1112 can, at operation 2508, determine, based on the difference 3006, the second DAC count model 2904. The second DAC count model 2904 can be a best-fit curve having a different, unique coefficient, k. The feedback controller 104 can utilize the coefficient in the mathematical model to adjust the actual power output 3008 to match the ideal power output 3202. More particularly, the controller 104 can select the DAC count model 2802 for which, when the first DAC count 3002 is used, the actual power output 3008 is expected. The selected next DAC count model 2802 may therefore be the one that has the same difference 3006 to the current DAC count model 2902 as the determined error.

[0269] The second DAC count model 2904 may represent the system operation more accurately than the first DAC count model 2902, allowing subsequent iterations of the control methodology to more accurately drive the transducer and reducing the difference 3006 after each iteration. For example, at a second iteration, at operation 2510, the processing device 1112 can send, e.g., to the excitation source 1118, the second DAC count 3012. For example,POMD04604SEC_WO01 PATENT the processing device 1112 can send the second DAC count 3012 to the DAC 1142 to cause the excitation source 1118 to drive the transducer 214 to deliver the target power to the target tissue. The second DAC count 3012 may be related to the target power output 3004 by the second DAC count model 2904 of the stored DAC count models 2802. Through its relation to the second DAC count model 2904, the second DAC count 3012 may be determined based on the difference 3006. The second DAC count model 2904 can allow the control methodology to re-base to the more representative model curve, for the next iteration and iterations afterward during which the actual power output 3008 is within a predetermined tolerance of the target power output 3004.

[0270] Some variation or deviation from a target power value may be expected in actual operation of the system and, thus, minor differences 3006 may not warrant adjusting the DAC count model 2802 used to determine DAC count. More particularly, the processing device 1112 may determine the second DAC count model 2904 (and the second DAC count 3012 of the second DAC count model 2904) in response to determining that the difference 3006 is greater than a threshold. The threshold may, for example, be an upper or lower limit of expected variation in the control methodology. For example, the threshold could be 0.50% of the target power output 3004. Accordingly, when the difference 3006 is greater than the threshold, the controller 104 can adjust the DAC count model 2802 by determining and implementing the second DAC count model 2904. If, however, the difference 3006 is less than the threshold, the controller 104 can continue to use the first DAC count model 2902 to control the excitation source 1118.

[0271] It will be appreciated that the first DAC count model 2902 and the second DAC count model 2904 may have similar governing equations with the exception of the coefficient, k. Furthermore, the coefficients may be constants. Accordingly, the first DAC count model 2902 relates the first DAC count 3002 to the target power output 3004 by a first constant coefficient, and the second DAC count model 2904 can relate the second DAC count 3012 to the target power output 3004 by a second constant coefficient. The second constant coefficient can be different than the first constant coefficient.

[0272] The difference between the constant coefficients of the DAC count models 2802 may correspond directly to the difference 3006 between the actual power output 3008 and the target power output 3004. For example, when the difference 3006 is positive (the actual power output 3008 is higher than the target power output 3004) the second constant coefficient may be more than the first constant coefficient. For example, the first constantPOMD04604SEC_WO01 PATENT coefficient may be -180 and the second constant coefficient may be -172. By contrast, when the difference 3006 is negative (the actual power output 3008 is lower than the target power output 3004) the second constant coefficient may be less than the first constant coefficient. For example, the first constant coefficient may be -180 and the second constant coefficient may be -188.

[0273] The adjustment to the DAC count model 2802, as determined based on differences 3006 between sensed or estimated actual power output 3008 and target power output 3004, can result in a reduction or elimination of oscillations in output power during energy delivery. Furthermore, the adjustment can provide greater stability in steady-state power. Such benefits derive from the use of a model that accurately reflects actual power delivery, based on inherent operational characteristics of the system, e.g., the controller 104 and / or the tissue treatment catheter 102.

[0274] Referring to FIG. 31 , a graph of steady state power output of an ultrasound transducer using proportional integral control is shown in accordance with certain embodiments. The graph represents control using a PI or PID controller 104, rather than the DAC count models 2802 described above. It will be appreciated that, due to the limitations of such control methodologies in the context of controlling nonlinear processes, the steady state power accuracy (the ratio of actual power output 3008 to target power output 3004) can vary significantly. More particularly, power accuracy according to such control methodologies, when the process is being controlled at a steady state power output 2602, has been shown to vary between a lower limit 3102 of 99.5% and an upper limit 3104 of 100.5%, a variation of up to 1%.

[0275] Referring to FIG. 32, a graph of steady state power output of an ultrasound transducer using DAC count models is shown in accordance with certain embodiments. Implementation of the controller 104 using the DAC count models 2802 to control power delivery can reduce the variation in power accuracy. More particularly, power accuracy according to the control methodologies described above, when the process is being controlled at a steady state power output 2602, has been shown to vary between a lower limit 3202 of 99.75% and an upper limit 3204 of 100.25%, a variation of less than 1%, e.g., 0.5% or less.

[0276] The more accurate power delivery provided by the control methodology described above can facilitate therapeutic applications that may not be possible using existing control methodologies. Depending on a target anatomy, a range of power deliveries that will be acceptable for effective treatment may change. A depth or a range of depths to whichPOMD04604SEC_WO01 PATENT tissue may be affected by the delivered energy without adversely affecting treatment may change. For example, whereas renal arteries may be effectively treated when energy is delivered to a depth of 1-6 mm, such depths may be excessive for other anatomies, e.g., a hepatic artery. The hepatic artery may require treatment depths in a range of 1-4 mm, e.g., 1- 2 mm for some segments of the hepatic artery. Similarly, denervation near a renal parenchyma or a pulmonary artery could require tighter control of energy delivery (and therefore, tissue ablation depth) than may be provided by existing control methodologies. On the other hand, the control methodology described above may allow for improved power delivery accuracy, which results in better control of ablation depth, and can be suitable for a wider range of anatomies, allowing tissue to be affected close to a sensitive zone, such as a vascular media, without touching the sensitive area.

[0277] Embodiments of a tissue treatment system are described above. More particularly, embodiments of the tissue treatment system or a controller thereof are described, either explicitly or implicitly. The following paragraphs summarize some of the described embodiments. More particularly, embodiments are described in the following enumerated examples.

[0278] Example 1. A tissue treatment system, comprising: a fluid supply subsystem including a fluid supply actuator to deliver fluid to a catheter through a supply line and a supply pressure sensor to detect a fluid pressure of the fluid in the supply line; and a processing device communicatively coupled to the fluid supply subsystem, wherein the processing device is configured to: monitor the fluid pressure, send, in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate, send, in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate, and send, in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

[0279] Example 2. The tissue treatment system of example 1 , wherein the second flow rate is lower than the first flow rate, and wherein the third flow rate is lower than the second flow rate.

[0280] Example 3. The tissue treatment system of any of examples 1 or 2, wherein the first flow rate is 30 mL / min, wherein the second flow rate is 15 mL / min, and wherein the third flow rate is 5 mL / min.POMD04604SEC_WO01 PATENT

[0281] Example 4. The tissue treatment system of any of examples 1 through 3, wherein the first pressure value is lower than the second pressure value.

[0282] Example 5. The tissue treatment system of any of examples 1 through 4, wherein the first pressure value is -2 psi or 0 psi, and wherein the second pressure value is 4 psi or 5 psi.

[0283] Example 6. The tissue treatment system of any of examples 1 through 5, wherein the processing device is further configured to send, in response to the fluid pressure being below a threshold pressure value after being above a third pressure value, a fourth drive signal to cause the fluid supply actuator to deliver fluid at a fourth flow rate.

[0284] Example 7. The tissue treatment system of example 6, wherein the third pressure value is higher than the threshold pressure value.

[0285] Example 8. The tissue treatment system of any of examples 6 or 7, wherein the third pressure value is 10.1 psi and the threshold pressure value is 9.6 psi.

[0286] Example 9. The tissue treatment system of any of examples 1 through 8, wherein fluid is delivered through a supply valve to the supply line, and wherein the supply valve is fully open when the fluid supply actuator is delivering fluid.

[0287] Example 10. The tissue treatment system of any of examples 1 through 9, wherein the fluid supply actuator includes a motor, and wherein the first drive signal, the second drive signal, and the third drive signal cause the motor to operate at respective motor speeds.

[0288] Example 11. A tissue treatment system, comprising: a fluid supply subsystem including a fluid return actuator to remove fluid from a catheter through a return line and a return pressure sensor to detect a fluid pressure of the fluid in the return line; and a processing device communicatively coupled to the fluid supply subsystem, wherein the processing device is configured to: monitor the fluid pressure, send, in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid return actuator to remove fluid at a first flow rate, send, in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid supply actuator to remove fluid at a second flow rate, and stop, in response to the fluid pressure being below the second vacuum value, the fluid supply actuator.

[0289] Example 12. The tissue treatment system of example 11, wherein the first vacuum value is higher than the second vacuum value.POMD04604SEC_WO01 PATENT

[0290] Example 13. The tissue treatment system of any of examples 11 or 12, wherein the first vacuum value is -10 psi, and wherein the second vacuum value is -12 psi.

[0291] Example 14. A method, comprising: monitoring, by a processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line, wherein the fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure; sending, by the processing device in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate, sending, by the processing device in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate, and sending, by the processing device in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

[0292] Example 15. The method of example 14, wherein the second flow rate is lower than the first flow rate, and wherein the third flow rate is lower than the second flow rate.

[0293] Example 16. The method of any of examples 14 or 15, wherein the first flow rate is 30 mL / min, wherein the second flow rate is 15 mL / min, and wherein the third flow rate is 5 mL / min.

[0294] Example 17. The method of any of examples 14 through 16, wherein the first pressure value is lower than the second pressure value.

[0295] Example 18. The method of any of examples 14 through 17, wherein the first pressure value is -2 psi or 0 psi, and wherein the second pressure value is 4 psi or 5 psi.

[0296] Example 19. The method of any of examples 14 through 18 further comprising sending, by the processing device in response to the fluid pressure being below a threshold pressure value after being above a third pressure value, a fourth drive signal to cause the fluid supply actuator to deliver fluid at a fourth flow rate.

[0297] Example 20. The method of example 19, wherein the third pressure value is higher than the threshold pressure value.

[0298] Example 21. The method of any of examples 19 or 20, wherein the third pressure value is 10.1 psi and the threshold pressure value is 9.6 psi.POMD04604SEC_WO01 PATENT

[0299] Example 22. The method of any of examples 14 through 21, wherein fluid is delivered through a supply valve to the supply line, and wherein the supply valve is fully open when the fluid supply actuator is delivering fluid.

[0300] Example 23. The method of any of examples 14 through 22, wherein the fluid supply actuator includes a motor, and wherein the first drive signal, the second drive signal, and the third drive signal cause the motor to operate at respective motor speeds.

[0301] Example 24. A method, comprising: monitoring, by a processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line, wherein the fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure; sending, by the processing device in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid supply actuator to remove fluid at a first flow rate; sending, by the processing device in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid supply actuator to remove fluid at a second flow rate; and stopping, by the processing device in response to the fluid pressure being below the second vacuum value, the fluid supply actuator.

[0302] Example 25. The method of example 24, wherein the first vacuum value is higher than the second vacuum value.

[0303] Example 26. The method of any of examples 24 or 25, wherein the first vacuum value is -10 psi, and wherein the second vacuum value is -12 psi.

[0304] Example 27. A non-transitory computer readable medium storing instructions which, when executed by a processing device of a tissue treatment system, causes the tissue treatment system to: monitor, by the processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line, wherein the fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure; send, by the processing device in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate, send, by the processing device in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate, and send, by the processing device in response to the fluid pressurePOMD04604SEC_WO01 PATENT being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

[0305] Example 28. The non-transitory computer readable medium of example 27, wherein the second flow rate is lower than the first flow rate, and wherein the third flow rate is lower than the second flow rate.

[0306] Example 29. The non-transitory computer readable medium of any of examples 27 or 28, wherein the first flow rate is 30 mL / min, wherein the second flow rate is 15 mL / min, and wherein the third flow rate is 5 mL / min.

[0307] Example 30. The non-transitory computer readable medium of any of examples 27 through 29, wherein the first pressure value is lower than the second pressure value.

[0308] Example 31. The non-transitory computer readable medium of any of examples 27 through 30, wherein the first pressure value is -2 psi or 0 psi, and wherein the second pressure value is 4 psi or 5 psi.

[0309] Example 32. The non-transitory computer readable medium of example 27, wherein the instructions, when executed by the processing device, further cause the tissue treatment system to send, by the processing device in response to the fluid pressure being below a threshold pressure value after being above a third pressure value, a fourth drive signal to cause the fluid supply actuator to deliver fluid at a fourth flow rate.

[0310] Example 33. The non-transitory computer readable medium of example 32, wherein the third pressure value is higher than the threshold pressure value.

[0311] Example 34. The non-transitory computer readable medium of any of examples 32 or 33, wherein the third pressure value is 10.1 psi and the threshold pressure value is 9.6 psi.

[0312] Example 35. The non-transitory computer readable medium of any of examples 27 through 34, wherein fluid is delivered through a supply valve to the supply line, and wherein the supply valve is fully open when the fluid supply actuator is delivering fluid.

[0313] Example 36. The non-transitory computer readable medium of any of examples 27 through 35, wherein the fluid supply actuator includes a motor, and wherein the first drive signal, the second drive signal, and the third drive signal cause the motor to operate at respective motor speeds.

[0314] Example 37. A non-transitory computer readable medium storing instructions which, when executed by a processing device of a tissue treatment system, causes the tissuePOMD04604SEC_WO01 PATENT treatment system to: monitor, by the processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line, wherein the fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure; send, by the processing device in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid supply actuator to remove fluid at a first flow rate; send, by the processing device in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid supply actuator to remove fluid at a second flow rate; and stop, by the processing device in response to the fluid pressure being below the second vacuum value, the fluid supply actuator.

[0315] Example 38. The non-transitory computer readable medium of example 37, wherein the first vacuum value is higher than the second vacuum value.

[0316] Example 39. The non-transitory computer readable medium of any of examples 37 or 38, wherein the first vacuum value is -10 psi, and wherein the second vacuum value is -12 psi.

[0317] Example 40. A method comprising determining that a first balloon pressure is below a first balloon pressure threshold, sending a first drive signal to cause the fluid actuator to use a motor speed at a first flow rate, determining that a second balloon pressure is below a second balloon threshold, the second balloon threshold being above the first balloon pressure threshold, sending a second drive signal to cause the fluid actuator to use a motor speed at a second flow rate, the second flow rate being below the first flow rate, monitoring the balloon pressure for a period of time, determining that a third balloon pressure is below a third balloon threshold, the third balloon threshold being above the second balloon pressure threshold, sending a third drive signal to cause the fluid actuator to use a motor speed at a third flow rate, the third flow rate being below the second flow rate.

[0318] Example 40. A tissue treatment system comprising a means for inflating a complaint ballon to a working inflation pressure in 15 seconds or less.

[0319] Example 41. A tissue treatment system comprising a means for inflating a complaint ballon to a working inflation pressure in 10 seconds or less.

[0320] Example 42. A tissue treatment system comprising a means for inflating a complaint ballon to a working inflation pressure in 5 seconds or less.

[0321] Example I. A controller of a tissue treatment system, comprising: an excitation source to provide energy to an ultrasound transducer of a catheter; a memoryPOMD04604SEC_WO01 PATENT storing digital-to-analog (DAC) count models relating DAC count of the excitation source to power output of the ultrasound transducer; and a processing device communicatively coupled to the excitation source and the memory, wherein the processing device is configured to: send, to the excitation source, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models, determine a difference between an actual power output of the ultrasound transducer and the target power output, and determine, based on the difference, a second DAC count model of the DAC count models, and send, to the excitation source, a second DAC count related to the target power output by the second DAC count model.

[0322] Example II. The controller of example I, wherein the DAC count models are nonlinear models based on nonlinear least squares.

[0323] Example III. The controller of any of examples I to II, wherein the first DAC count model relates the first DAC count to the target power output by a first constant coefficient, and wherein the second DAC count model relates the second DAC count to the target power output by a second constant coefficient different than the first constant coefficient.

[0324] Example IV. The controller of example III, wherein, when the difference is positive, the second constant coefficient is more than the first constant coefficient.

[0325] Example V. The controller of example III, wherein, when the difference is negative, the second constant coefficient is less than the first constant coefficient.

[0326] Example VI. The controller of any of examples I to V, wherein determining the difference includes applying a low pass filter to a return electrical signal to determine the actual power output, and comparing the actual power output to the target power output.

[0327] Example VII. The controller of example 6, wherein the return electrical signal has a time interval of 5 to 50 ms.

[0328] Example VIII. The controller of any of examples I to VII, wherein generating the second DAC count model is in response to determining that the difference is greater than a threshold.

[0329] Example IX. The controller of any of examples I to VIII further comprising the catheter, wherein the catheter and the ultrasound transducer are insertable into a body lumen.

[0330] Example X. A method, comprising: storing, by a memory of a controller of a tissue treatment system, digital-to-analog (DAC) count models relating DAC count of anPOMD04604SEC_WO01 PATENT excitation source to power output of an ultrasound transducer; sending, by a processing device of the controller to the excitation source, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models; determining, by the processing device, a difference between an actual power output of the ultrasound transducer and the target power output; determining, by the processing device based on the difference, a second DAC count model of the DAC count models; and sending, by the processing device to the excitation source, a second DAC count related to the target power output by the second DAC count model.

[0331] Example XI. The method of example X, wherein the DAC count models are nonlinear models based on nonlinear least squares.

[0332] Example XII. The method of any of examples X to XI, wherein the first DAC count model relates the first DAC count to the target power output by a first constant coefficient, and wherein the second DAC count model relates the second DAC count to the target power output by a second constant coefficient different than the first constant coefficient.

[0333] Example XIII. The method of example XII, wherein, when the difference is positive, the second constant coefficient is more than the first constant coefficient.

[0334] Example XIV. The method of example XII, wherein, when the difference is negative, the second constant coefficient is less than the first constant coefficient.

[0335] Example XV. The method of any of examples X to XIV, wherein determining the difference includes applying a low pass filter to a return electrical signal to determine the actual power output, and comparing the actual power output to the target power output.

[0336] Example XVI. The method of example XV, wherein the return electrical signal has a time interval of 5 to 50 ms.

[0337] Example XVII. The method of any of examples X to XVI, wherein generating the second DAC count model is in response to determining that the difference is greater than a threshold.

[0338] Example XVIII. A non-transitory computer readable medium storing instructions which, when executed by a processing device of a controller of a tissue treatment system, causes the tissue treatment system to: store, by a memory of the controller, digital-to- analog (DAC) count models relating DAC count of an excitation source to power output of an ultrasound transducer; send, to the excitation source by the processing device, a first DAC count related to a target power output of the ultrasound transducer by a first DAC countPOMD04604SEC_WO01 PATENT model of the DAC count models; determine, by the processing device, a difference between an actual power output of the ultrasound transducer and the target power output; determine, by the processing device based on the difference, a second DAC count model of the DAC count models; and send, to the excitation source by the processing device, a second DAC count related to the target power output by the second DAC count model.

[0339] Example XIX. The non-transitory computer readable medium of example XVIII, wherein the DAC count models are nonlinear models based on nonlinear least squares.

[0340] Example XX. The non-transitory computer readable medium of any of examples XVIII to XIX, wherein the first DAC count model relates the first DAC count to the target power output by a first constant coefficient, and wherein the second DAC count model relates the second DAC count to the target power output by a second constant coefficient different than the first constant coefficient.

[0341] Example XXI. The non-transitory computer readable medium of example XX, wherein, when the difference is positive, the second constant coefficient is more than the first constant coefficient.

[0342] Example XXII. The non-transitory computer readable medium of example XX, wherein, when the difference is negative, the second constant coefficient is less than the first constant coefficient.

[0343] Example XXIII. The non-transitory computer readable medium of any of examples XVIII to XXII, wherein determining the difference includes applying a low pass filter to a return electrical signal to determine the actual power output, and comparing the actual power output to the target power output.

[0344] Example XXIV. The non-transitory computer readable medium of example XXIII, wherein the return electrical signal has a time interval of 5 to 50 ms.

[0345] Example XXV. The non-transitory computer readable medium of any of examples XVIII to XXIV, wherein generating the second DAC count model is in response to determining that the difference is greater than a threshold.

[0346] 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.

Claims

POMD04604SEC_WO01 PATENTCLAIMSWhat is claimed is:

1. A tissue treatment system, comprising: a fluid supply subsystem including a fluid supply actuator to deliver fluid to a catheter through a supply line and a supply pressure sensor to detect a fluid pressure of the fluid in the supply line; and a processing device communicatively coupled to the fluid supply subsystem, wherein the processing device is configured to: monitor the fluid pressure, and regulate a fluid flow rate based on the monitored fluid pressure during a balloon inflation process, wherein in an initial stage of the inflation process, the balloon is inflated more aggressively than in later stages.

2. The tissue treatment system of claim 1, wherein regulating the fluid flow rate comprises: sending, in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate, sending, in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate, and sending, in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

3. The tissue treatment system of claim 2, wherein the second flow rate is lower than the first flow rate, and wherein the third flow rate is lower than the second flow rate.

4. The tissue treatment system of any of claims 2 or 3, wherein the first flow rate is 30 mL / min, wherein the second flow rate is 15 mL / min, and wherein the third flow rate is 5 mL / min.POMD04604SEC_WO01 PATENT5. The tissue treatment system of any of claims 2 through 4, wherein the first pressure value is lower than the second pressure value.

6. The tissue treatment system of any of claims 2 through 5, wherein the first pressure value is -2 psi or 0 psi, and wherein the second pressure value is 4 psi or 5 psi.

7. The tissue treatment system of any of claims 2 through 6, wherein the processing device is further configured to send, in response to the fluid pressure being below a threshold pressure value after being above a third pressure value, a fourth drive signal to cause the fluid supply actuator to deliver fluid at a fourth flow rate.

8. The tissue treatment system of claim 7, wherein the third pressure value is higher than the threshold pressure value.

9. The tissue treatment system of any of claims 7 or 8, wherein the third pressure value is 10.1 psi and the threshold pressure value is 9.6 psi.

10. The tissue treatment system of any of claims 1 through 9, wherein fluid is delivered through a supply valve to the supply line, and wherein the supply valve is fully open when the fluid supply actuator is delivering fluid.

11. The tissue treatment system of any of claims 2 through 10, wherein the fluid supply actuator includes a motor, and wherein the first drive signal, the second drive signal, and the third drive signal cause the motor to operate at respective motor speeds.

12. A tissue treatment system, comprising: a fluid supply subsystem including a fluid return actuator to remove fluid from a catheter through a return line and a return pressure sensor to detect a fluid pressure of the fluid in the return line; and a processing device communicatively coupled to the fluid supply subsystem, wherein the processing device is configured to: monitor the fluid pressure, send, in response to the fluid pressure being above a first vacuum value, a firstPOMD04604SEC_WO01 PATENT drive signal to cause the fluid return actuator to remove fluid at a first flow rate, send, in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid return actuator to remove fluid at a second flow rate, and stop, in response to the fluid pressure being below the second vacuum value, the fluid return actuator.

13. The tissue treatment system of claim 12, wherein the first vacuum value is higher than the second vacuum value.

14. The tissue treatment system of any of claims 12 or 13, wherein the first vacuum value is -10 psi, and wherein the second vacuum value is -12 psi.

15. A method, comprising: monitoring, by a processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line, wherein the fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure; regulating a fluid flow rate based on the monitored fluid pressure during a balloon inflation process, wherein in an initial stage of the inflation process, the balloon is inflated more aggressively than in later stages.

16. The method of claim 15, wherein regulating the fluid flow rate comprises: sending, by the processing device in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate, sending, by the processing device in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate, and sending, by the processing device in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.POMD04604SEC_WO01 PATENT17. The method of claim 16, wherein the second flow rate is lower than the first flow rate, and wherein the third flow rate is lower than the second flow rate.

18. The method of any of claims 16 or 17, wherein the first flow rate is 30 mL / min, wherein the second flow rate is 15 mL / min, and wherein the third flow rate is 5 mL / min.

19. The method of any of claims 16 through 18, wherein the first pressure value is lower than the second pressure value.

20. The method of any of claims 16 through 19, wherein the first pressure value is -2 psi or 0 psi, and wherein the second pressure value is 4 psi or 5 psi.

21. The method of any of claims 16 through 20 further comprising sending, by the processing device in response to the fluid pressure being below a threshold pressure value after being above a third pressure value, a fourth drive signal to cause the fluid supply actuator to deliver fluid at a fourth flow rate.

22. The method of claim 21, wherein the third pressure value is higher than the threshold pressure value.

23. The method of any of claims 21 or 22, wherein the third pressure value is 10.1 psi and the threshold pressure value is 9.6 psi.

24. The method of any of claims 16 through 23, wherein fluid is delivered through a supply valve to the supply line, and wherein the supply valve is fully open when the fluid supply actuator is delivering fluid.

25. The method of any of claims 16 through 24, wherein the fluid supply actuator includes a motor, and wherein the first drive signal, the second drive signal, and the third drive signal cause the motor to operate at respective motor speeds.POMD04604SEC_WO01 PATENT26. A method, comprising: monitoring, by a processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a return line, wherein the fluid supply subsystem includes a fluid return actuator to remove the fluid from a catheter through the return line and a return pressure sensor to detect the fluid pressure in the return line; sending, by the processing device in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid return actuator to remove fluid at a first flow rate; sending, by the processing device in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid return actuator to remove fluid at a second flow rate; and stopping, by the processing device in response to the fluid pressure being below the second vacuum value, the fluid return actuator.

27. The method of claim 26, wherein the first vacuum value is higher than the second vacuum value.

28. The method of any of claims 26 or 27, wherein the first vacuum value is -10 psi, and wherein the second vacuum value is -12 psi.

29. A non-transitory computer readable medium storing instructions which, when executed by a processing device of a tissue treatment system, causes the tissue treatment system to: monitor, by the processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a supply line, wherein the fluid supply subsystem includes a fluid supply actuator to deliver the fluid to a catheter through the supply line and a supply pressure sensor to detect the fluid pressure; regulate a fluid flow rate based on the monitored fluid pressure during a balloon inflation process, wherein in an initial stage of the inflation process, the balloon is inflated more aggressively than in later stages.POMD04604SEC_WO01 PATENT30. The non-transitory computer readable medium of claim 29, wherein regulating the fluid flow rate comprises: sending, by the processing device in response to the fluid pressure being below a first pressure value, a first drive signal to cause the fluid supply actuator to deliver fluid at a first flow rate, sending, by the processing device in response to the fluid pressure being above the first pressure value and below a second pressure value, a second drive signal to cause the fluid supply actuator to deliver fluid at a second flow rate, and sending, by the processing device in response to the fluid pressure being above the second pressure value, a third drive signal to cause the fluid supply actuator to deliver fluid at a third flow rate.

31. The non-transitory computer readable medium of claim 30, wherein the second flow rate is lower than the first flow rate, and wherein the third flow rate is lower than the second flow rate.

32. The non-transitory computer readable medium of any of claims 30 or 31, wherein the first flow rate is 30 mL / min, wherein the second flow rate is 15 mL / min, and wherein the third flow rate is 5 mL / min.

33. The non-transitory computer readable medium of any of claims 30 through 32, wherein the first pressure value is lower than the second pressure value.

34. The non-transitory computer readable medium of any of claims 30 through 33, wherein the first pressure value is -2 psi or 0 psi, and wherein the second pressure value is 4 psi or 5 psi.

35. The non-transitory computer readable medium of any of claims 30 through 34, wherein the instructions, when executed by the processing device, further cause the tissue treatment system to send, by the processing device in response to the fluid pressure being below a threshold pressure value after being above a third pressure value, a fourth drive signal to cause the fluid supply actuator to deliver fluid at a fourth flow rate.POMD04604SEC_WO01 PATENT36. The non-transitory computer readable medium of claim 35, wherein the third pressure value is higher than the threshold pressure value.

37. The non-transitory computer readable medium of any of claim 35 or 36, wherein the third pressure value is 10.1 psi and the threshold pressure value is 9.6 psi.

38. The non-transitory computer readable medium of any of claims 30 through 37, wherein fluid is delivered through a supply valve to the supply line, and wherein the supply valve is fully open when the fluid supply actuator is delivering fluid.

39. The non-transitory computer readable medium of any of claims 30 through 38, wherein the fluid supply actuator includes a motor, and wherein the first drive signal, the second drive signal, and the third drive signal cause the motor to operate at respective motor speeds.

40. A non-transitory computer readable medium storing instructions which, when executed by a processing device of a tissue treatment system, causes the tissue treatment system to: monitor, by the processing device communicatively coupled to a fluid supply subsystem, a fluid pressure of a fluid in a return line, wherein the fluid supply subsystem includes a fluid return actuator to remove the fluid from a catheter through the return line and a return pressure sensor to detect the fluid pressure in the return line; send, by the processing device in response to the fluid pressure being above a first vacuum value, a first drive signal to cause the fluid return actuator to remove fluid at a first flow rate; send, by the processing device in response to the fluid pressure being below the first vacuum value and above a second vacuum value, a second drive signal to cause the fluid supply actuator to remove fluid at a second flow rate; and stop, by the processing device in response to the fluid pressure being below the second vacuum value, the fluid supply actuator.

41. The non-transitory computer readable medium of claim 40, wherein the first vacuum value is higher than the second vacuum value.POMD04604SEC_WO01 PATENT42. The non-transitory computer readable medium of any of claims 40 or 41, wherein the first vacuum value is -10 psi, and wherein the second vacuum value is -12 psi.

43. A controller of a tissue treatment system, comprising: an excitation source to provide energy to an ultrasound transducer of a catheter; a memory storing digital-to-analog (DAC) count models relating DAC count of the excitation source to power output of the ultrasound transducer; and a processing device communicatively coupled to the excitation source and the memory, wherein the processing device is configured to: send, to the excitation source, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models, determine a difference between an actual power output of the ultrasound transducer and the target power output, and determine, based on the difference, a second DAC count model of the DAC count models, and send, to the excitation source, a second DAC count related to the target power output by the second DAC count model.

44. The controller of claim 43, wherein the DAC count models are nonlinear models based on nonlinear least squares.

45. The controller of any of claims 43 to 44, wherein the first DAC count model relates the first DAC count to the target power output by a first constant coefficient, and wherein the second DAC count model relates the second DAC count to the target power output by a second constant coefficient different than the first constant coefficient.

46. The controller of claim 45, wherein, when the difference is positive, the second constant coefficient is more than the first constant coefficient.POMD04604SEC_WO01 PATENT47. The controller of claim 45, wherein, when the difference is negative, the second constant coefficient is less than the first constant coefficient.

48. The controller of any of claims 43 to 47, wherein determining the difference includes applying a low pass filter to a return electrical signal to determine the actual power output, and comparing the actual power output to the target power output.

49. The controller of claim 48, wherein the return electrical signal has a time interval of 5 to 50 ms.

50. The controller of any of claims 43 to 49, wherein determining the second DAC count model is in response to determining that the difference is greater than a threshold.

51. The controller of any of claims 43 to 50 further comprising the catheter, wherein the catheter and the ultrasound transducer are insertable into a body lumen.

52. A method, comprising: storing, by a memory of a controller of a tissue treatment system, digital-to- analog (DAC) count models relating DAC count of an excitation source to power output of an ultrasound transducer; sending, by a processing device of the controller to the excitation source, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models; determining, by the processing device, a difference between an actual power output of the ultrasound transducer and the target power output; determining, by the processing device based on the difference, a second DAC count model of the DAC count models; and sending, by the processing device to the excitation source, a second DAC count related to the target power output by the second DAC count model.

53. The method of claim 52, wherein the DAC count models are nonlinear models based on nonlinear least squares.POMD04604SEC_WO01 PATENT54. The method of any of claims 52 to 53, wherein the first DAC count model relates the first DAC count to the target power output by a first constant coefficient, and wherein the second DAC count model relates the second DAC count to the target power output by a second constant coefficient different than the first constant coefficient.

55. The method of claim 54, wherein, when the difference is positive, the second constant coefficient is more than the first constant coefficient.

56. The method of claim 54, wherein, when the difference is negative, the second constant coefficient is less than the first constant coefficient.

57. The method of any of claims 52 to 56, wherein determining the difference includes applying a low pass filter to a return electrical signal to determine the actual power output, and comparing the actual power output to the target power output.

58. The method of claim 57, wherein the return electrical signal has a time interval of 5 to 50 ms.

59. The method of any of claims 52 to 58, wherein determining the second DAC count model is in response to determining that the difference is greater than a threshold.

60. A non-transitory computer readable medium storing instructions which, when executed by a processing device of a controller of a tissue treatment system, causes the tissue treatment system to: store, by a memory of the controller, digital-to-analog (DAC) count models relating DAC count of an excitation source to power output of an ultrasound transducer; send, to the excitation source by the processing device, a first DAC count related to a target power output of the ultrasound transducer by a first DAC count model of the DAC count models; determine, by the processing device, a difference between an actual power output of the ultrasound transducer and the target power output; determine, by the processing device based on the difference, a second DAC count model of the DAC count models; andPOMD04604SEC_WO01 PATENT send, to the excitation source by the processing device, a second DAC count related to the target power output by the second DAC count model.

61. The non-transitory computer readable medium of claim 60, wherein the DAC count models are nonlinear models based on nonlinear least squares.

62. The non-transitory computer readable medium of any of claims 60 to 61, wherein the first DAC count model relates the first DAC count to the target power output by a first constant coefficient, and wherein the second DAC count model relates the second DAC count to the target power output by a second constant coefficient different than the first constant coefficient.

63. The non-transitory computer readable medium of claim 62, wherein, when the difference is positive, the second constant coefficient is more than the first constant coefficient.

64. The non-transitory computer readable medium of claim 62, wherein, when the difference is negative, the second constant coefficient is less than the first constant coefficient.

65. The non-transitory computer readable medium of any of claims 60 to 67, wherein determining the difference includes applying a low pass filter to a return electrical signal to determine the actual power output, and comparing the actual power output to the target power output.

66. The non-transitory computer readable medium of claim 65, wherein the return electrical signal has a time interval of 5 to 50 ms.

67. The non-transitory computer readable medium of any of claims 60 to 66, wherein determining the second DAC count model is in response to determining that the difference is greater than a threshold.

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