Tissue disruption acoustic / patient binding system and method

Abstract

Provided herein are histolytic treatment systems configured for the treatment of tissue, which may include any number of features. Provided herein are systems and methods that provide effective non-invasive and minimally invasive treatments, diagnostics, and research methods. Specifically, provided herein are optimized systems and methods that provide targeted, effective histolysis in a variety of different regions and under a variety of different conditions without causing unwanted tissue damage to intervening / non-target tissues or structures. Specifically, provided herein are systems and methods for acoustically coupling a histolytic treatment system to a patient's skin to provide targeted, effective histolysis in a variety of different regions and under a variety of different conditions without causing unwanted tissue damage to intervening / non-target tissues or structures.

Description

[Technical Field]

[0001] Cross-Reference to Related Applications

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 041,072, filed on June 18, 2020, which is incorporated herein by reference in its entirety. Incorporation by Reference

[0002]

[0002] All publications and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0003]

[0003] The present disclosure details a novel high-intensity focused ultrasound therapy (HITU) system configured to provide acoustic cavitation, methods, devices and procedures for minimally invasive and non-invasive treatment of healthy, diseased and / or injured tissue. The acoustic cavitation systems and methods described herein, also referred to as histotripsy, may include a transducer, driving electronics, a positioning robot, an imaging system, and integrated treatment planning and control software to provide comprehensive treatment and therapy for a patient's soft tissue. [Background Art]

[0004]

[0004] Histotripsy, or pulsed ultrasonic cavitation therapy, is a technique in which extremely short high-power bursts of acoustic energy produce controlled cavitation (microbubble formation) within a focal volume. The violent expansion and collapse of these microbubbles mechanically homogenizes cells and tissue structures within the focal volume. This is an outcome that is very different from the coagulative necrosis characteristic of thermal ablation. Operating within the scope of non-thermal histotripsy requires delivering acoustic energy in the form of high-amplitude acoustic pulses at a low duty cycle.

[0005]

[0005] Compared to conventional focused ultrasound techniques, tissue disruption has the following important advantages: 1) the disruption process at the focus is mechanical rather than thermal; 2) cavitation appears brighter in ultrasound imaging, thereby confirming correct targeting and localization of treatment; 3) treated tissue generally appears darker (less echogenic) in ultrasound imaging, though not always, so that the operator can see what has been treated; and 4) tissue disruption causes damage in a controlled and precise manner. It is important to emphasize that, unlike thermal ablation techniques such as microwave, radiofrequency and high-intensity focused ultrasound (HIFU) cryotherapy or radiation, tissue disruption relies on the mechanical action of cavitation for tissue destruction and does not rely on thermal, cold, or ionizing energy. [Overview of the project]

[0006]

[0006] An ultrasonic therapy system is provided, comprising: a coupling vessel configured to contact the patient's skin and at least partially filled with an acoustic coupling medium; an ultrasonic therapy transducer at least partially immersed in the acoustic coupling medium; and a robotic positioning arm coupled to the ultrasonic therapy transducer and configured to move the ultrasonic therapy transducer relative to the patient within the coupling vessel while maintaining acoustic coupling with the patient via the acoustic coupling medium.

[0007]

[0007] In some embodiments, the coupling vessel includes an open architecture that provides an open workspace for the robot positioning arm to move independently of the coupling vessel.

[0008]

[0008] In one embodiment, the binding container further includes a membrane configured to come into contact with the patient's skin.

[0009]

[0009] In another embodiment, the system further includes a bubble removal mechanism configured to remove bubbles and / or air between the membrane and the patient's skin.

[0010]

[0010] In another embodiment, the system includes a flexible boot assembly attached to a coupling vessel, configured to allow movement of an ultrasonic therapeutic transducer with an acoustic coupling medium contained within the coupling vessel.

[0011]

[0011] In some embodiments, the flexible boot assembly is further attached to an ultrasonic treatment transducer.

[0012]

[0012] In another embodiment, the system includes a fluid system comprising an acoustic coupling medium source, a cooling and degassing system, and a programmable control system configured to automatically control the fluid level of the acoustic coupling medium in the coupling vessel.

[0013]

[0013] In some embodiments, the fluid system is separated from the robot positioning arm.

[0014]

[0014] In another embodiment, the system includes a support arm configured to support a coupling container.

[0015]

[0015] In one embodiment, the support arm is configured to move independently of the robot positioning arm. In another embodiment, the support arm is connected to a fluid system. In yet another embodiment, the support arm is connected to a treatment cart of a tissue disruption system. In yet another embodiment, the support arm is connected to a patient bed. Depending on the embodiment, the support arm is movable between 4 and 7 degrees of freedom.

[0016]

[0016] In one embodiment, the fluid system is configured to communicate with sensors located on or inside the UMC.

[0017]

[0017] In another embodiment, the fluid system further includes one or more sensors configured to detect parameters of the fluid system or of the acoustic coupling medium.

[0018]

[0018] Depending on the embodiment, the sensor is selected from the group consisting of a pressure sensor, a coupled medium level sensor, an optical sensor, a dissolved gas concentration sensor, a bubble or particulate sensor, a temperature sensor, a flow rate sensor, a cavitation detection sensor, and a proximity sensor.

[0019]

[0019] In one embodiment, the coupling container includes a frame.

[0020]

[0020] In another embodiment, the frame comprises a biocompatible material. Depending on the embodiment, the frame comprises a thermoplastic elastomer selected from the group consisting of polyurethane, polystyrene copolymer, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyrate), poly(phosphatine), polyester, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl methyl acrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, polybutylene, aliphatic polyester, glycerol, poly(amino acid), copoli(ether-ester), polyalkylene oxalate, polyamide, poly(iminocarbonate), polyalkylene oxalate, polyoxaester, polyorthoester, polyphosphazene, and copolymers, block polymers, homopolymers, mixtures and combinations thereof.

[0021]

[0021] In one embodiment, the frame includes an upper frame and a lower frame, the upper frame being configured to be detachably attached to the lower frame.

[0022]

[0022] In some embodiments, the flexible boot assembly is removably attached to the upper frame. In other embodiments, the membrane is removably attached to the lower frame.

[0023]

[0023] In some embodiments, the flexible boot assembly and the membrane form a watertight seal between the upper frame and the lower frame.

[0024]

[0024] In another embodiment, the membrane is held in place between an upper frame and a lower frame.

[0025]

[0025] In some embodiments, the frame includes a first opening on a side of the frame configured to contact a patient's skin.

[0026]

[0026] In another embodiment, the membrane is attached to the frame and covers only the first opening. In some embodiments, the membrane includes a pouch configured to be positioned within a coupling container to cover the first opening. In one embodiment, the frame further includes a second opening opposite the first opening. In some embodiments, the pouch is configured to hang over an edge of the frame that defines the second opening.

[0027]

[0027] In one embodiment, the coupling container includes an additional flexible support structure comprising a bellows or a constraining mechanism.

[0028]

[0028] In another embodiment, the membrane comprises a biocompatible material configured to acoustically couple the coupling container and an acoustic coupling medium to the patient's skin with minimal or no trapped air bubbles. In some embodiments, the membrane comprises a thermoplastic elastomer selected from the group consisting of polyurethane, polystyrene copolymer, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyrate), poly(phosphazine), polyester, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl methacrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, polybutylene, aliphatic polyester, glycerol, poly(amino acid), copoly(ether-ester), polyalkylene oxalate, polyamide, poly(iminocarbonate), polyalkylene oxalate, polyoxaester, polyorthoester, polyphosphazene, and copolymers, block polymers, homopolymers, mixtures and combinations thereof.

[0029]

[0029] In one embodiment, the membrane has a thickness between 2 mm and 4 mm. In another embodiment, the membrane has a thickness between 2.5 mm and 3.5 mm.

[0030]

[0030] In some embodiments, the membrane comprises 10 to 80 percent by weight of oil. In other embodiments, the membrane comprises 40 to 60 percent by weight of oil.

[0031]

[0031] In some embodiments, the membrane has a tensile strength of >0.2 MPa.

[0032]

[0032] In another embodiment, the membrane further comprises a membrane frame disposed along an edge of the membrane. In some embodiments, the membrane frame is configured to interface with a coupling container.

[0033]

[0033] In some embodiments, the fluidic system is configured to deliver an acoustic coupling medium to the coupling container at a flow rate of 1 to 10 liters per minute. In some embodiments, the fluidic system is configured to maintain a dissolved oxygen level in the acoustic coupling medium at less than 40%. In other embodiments, the fluidic system is configured to maintain the temperature of the acoustic coupling medium between 10°C and 30°C.

[0034]

[0034] There is provided a method of acoustically coupling a treatment system to a patient's skin prior to treatment, comprising: receiving an ultrasound treatment system comprising a coupling container having a membrane, and an ultrasound treatment transducer configured to move freely within the coupling container; mechanically locking the coupling container and the ultrasound treatment transducer to prevent relative movement of the ultrasound treatment transducer with respect to the coupling container; delivering a flow of coupling medium to the coupling container to fill the coupling container and remove air from the coupling container; and placing the membrane in contact with the patient's skin.

[0035]

[0035] In some embodiments, the method further includes the step of rotating the binding container and the ultrasonic treatment transducer by about 90 degrees in order to position the binding container vertically, prior to the delivery step.

[0036]

[0036] In some embodiments, the delivery step further includes delivering a flow of the binding medium into the uppermost part of the binding container when the binding container is oriented vertically.

[0037]

[0037] In another embodiment, the method further includes visualizing the delivery of the flow of the binding medium to the container so that it can be seen through the membrane.

[0038]

[0038] In other embodiments, the method includes automatically filling the coupling vessel with an acoustic coupling medium by a fluid system separate from the coupling vessel.

[0039]

[0039] In one embodiment, automatic filling further includes automatic filling based on sensor feedback from within the coupling container or fluid system.

[0040]

[0040] In some embodiments, the sensor feedback includes the fluid level in the container. In another embodiment, the sensor feedback includes the detection of unwanted bubbles in the coupled container. In some embodiments, the sensor feedback includes the detection of unwanted cavitation in the coupled container.

[0041]

[0041] In some embodiments, the method further includes applying positive air pressure to the binding vessel before the delivery step in order to inspect the membrane or binding vessel for air leaks.

[0042]

[0042] In another embodiment, the method further includes exhausting air from the binding vessel. In some embodiments, the air is exhausted from a port located at the highest point of the binding vessel. In other embodiments, the air is exhausted from a central hole in the therapeutic transducer.

[0043]

[0043] In another embodiment, the method includes, prior to the placement step, rotating the coupling vessel and the ultrasonic treatment transducer back to a horizontal orientation.

[0044]

[0044] Novel features of the present invention are specifically described in the claims at the end. A better understanding of the features and advantages of the present invention can be gained by referring to the following detailed description, which describes exemplary embodiments in which the principles of the present invention are used, and the accompanying drawings. [Brief explanation of the drawing]

[0045] [Figure 1A]

[0045] This figure shows an ultrasound imaging and treatment system. [Figure 1B] This is a diagram showing an ultrasound imaging and treatment system. [Figure 2]

[0046] This figure shows one embodiment of a tissue disruption therapy and imaging system equipped with a binding system. [Figure 3A]

[0047] This is a detailed diagram showing the combined assembly and related components. [Figure 3B] This is a detailed diagram showing the combined assembly and related components. [Figure 3C] This is a detailed diagram showing the combined assembly and related components. [Figure 3D] This is a detailed diagram showing the combined assembly and related components. [Figure 3E] This is a detailed diagram showing the combined assembly and related components. [Figure 3F] This is a detailed diagram showing the combined assembly and related components. [Figure 4A]

[0048] Another diagram showing the combined assembly. [Figure 4B] Another diagram showing the combined assembly. [Figure 4C] Another diagram showing the combined assembly. [Figure 4D] Another diagram showing the combined assembly. [Figure 5A]

[0049] This figure shows another embodiment of the coupling assembly. [Figure 5B] This figure shows another embodiment of the coupling assembly. [Figure 5C] This figure shows another embodiment of the coupling assembly. [Figure 6A]

[0050] This figure shows one embodiment of a fluid system cart. [Figure 6B] This figure shows one embodiment of a fluid system cart. [Figure 7A]

[0051] This diagram shows a method for filling UMC with a binding medium. [Figure 7B] This diagram shows a method for filling UMC with a binding medium. [Figure 7C] This diagram shows a method for filling UMC with a binding medium. [Figure 7D] This diagram shows a method for filling UMC with a binding medium. [Figure 7E] This diagram shows a method for filling UMC with a binding medium. [Figure 7F] This diagram shows a method for filling UMC with a binding medium. [Figure 7G] This diagram shows a method for filling UMC with a binding medium. [Modes for carrying out the invention]

[0046]

[0052] The systems, methods, and devices of this disclosure can be used for open surgery, (laparoscopic and percutaneous) minimally invasive surgery, robotic surgery (integrated into robot-enabled medical systems), endoscopic or completely percutaneous non-enterpriseous acoustic cavitation for the treatment of healthy, diseased and / or injured tissue, including but not limited to tissue disruption, cutting, skeletonization, and ablation. Furthermore, due to its tissue-selective properties, tissue disruption can be used to form a cytoskeleton that enables subsequent tissue regeneration by de novo or stem cell and other adjuvant application. Finally, tissue disruption can be used to induce the release of delivery agents, such as chemotherapy and immunotherapy, by locally inducing drug release through the application of acoustic energy to a target. As described below, the acoustic cavitation system may include various subsystems, including carts, treatments, embedded imaging, robots, couplings, and software. The system may also include various other components, auxiliary and accessory devices, including but not limited to computers, cables and connectors, networking devices, power supplies, displays, drawers / storage units, doors, wheels, and various simulation and training tools. Any system, method, and means for causing, controlling, or carrying out tissue disruption, including any new related inventions disclosed herein, shall be deemed to be part of this disclosure.

[0047]

[0053] Figure 1A shows the tissue disruption system 100 according to this disclosure as a whole, including a therapeutic transducer 102, an imaging system 104, a display and control panel 106, a robotic positioning arm 108, and a cart 110. The system may further include an ultrasonic coupling interface and a coupling medium source, which are not shown.

[0048]

[0054] Figure 1B is a bottom view of the therapeutic transducer 102 and the imaging system 104. As shown in the figure, the imaging system may be positioned in the center of the therapeutic transducer. However, other embodiments may include an imaging system located elsewhere within the therapeutic transducer or directly integrated into the therapeutic transducer. Depending on the embodiment, the imaging system may be configured to generate real-time imaging at the focal point of the therapeutic transducer. The system may also allow for the placement of multiple imaging transducers within the therapeutic transducer to provide multiple fields of view of the target tissue simultaneously and to integrate those images into a single 3D image.

[0049]

[0055] The tissue disruption system may include one or more subsystems from a variety of subsystems, including a therapeutic subsystem capable of generating, applying, focusing, and executing acoustic cavitation / tissue disruption via one or more therapeutic transducers; an embedded imaging subsystem (or connection to an embedded imaging subsystem) enabling real-time visualization of the treatment site and tissue disruption effect throughout the procedure; and a robotic positioning subsystem further enabled to mechanically and / or electronically steer the therapeutic transducers, connect to / support a coupling subsystem to enable acoustic coupling between the therapeutic transducers and the patient, or interact with the coupling subsystem; software for communicating, controlling, and interface with the system and a computer-based control system (and other external systems); and various other components, auxiliary devices, and accessories, including one or more user interfaces and displays, associated guidance workflows, all of which function partially or in conjunction. The system may further include various fluid systems and fluid management components for supplying and storing fluids, including but not limited to pumps, valves and flow control, temperature and degassing control, and cleaning and suction functions. The system may also include various power supplies and protective devices.

[0050]

[0056] As described above, the tissue disruption system may include integrated imaging. However, in other embodiments, the tissue disruption system may be configured to interface with a separate imaging system such as a C-arm, fluoroscopy system, cone-beam CT, or MRI to provide real-time imaging during tissue disruption therapy. Depending on the embodiment, the tissue disruption system may be sized and configured to fit within a C-arm, fluoroscopy system, cone-beam CT, or MRI.

[0051] cart

[0057] Cart 110 can generally be configured in various ways and form factors based on specific uses and procedures. In some cases, the system may include multiple carts configured in similar or different configurations. In some embodiments, the cart may be configured and positioned for use in a radiological environment, and possibly in conjunction with imaging (e.g., CT, cone-beam CT, and / or MRI scans). In other embodiments, the cart can be positioned for use in operating rooms and sterile environments for open or laparoscopic surgery and endoscopic applications, or in robot-enabled operating rooms, and can be used alone or as part of a surgical robotic procedure in which a surgical robot performs specific tasks before, during, or after the use of the system and the implementation of acoustic cavitation / tissue disruption. Accordingly, depending on the procedure environment based on the embodiments described above, the cart may be positioned to provide ample workspace and access to various anatomical parts of the patient (e.g., torso, abdomen, flank, head, and neck), as well as workspace for other systems (e.g., anesthesia cart, laparoscopic tower, surgical robot, endoscopy tower, etc.).

[0052]

[0058] The cart may also be linked to and repositioned to a patient surface (e.g., a table or bed), including allowing the patient to change to numerous positions, angles, and orientations before, during, and after the procedure. The cart may further include the ability to interface and communicate with one or more external imaging or image data management and communication systems of one or more modalities, not limited to ultrasound, CT, fluoroscopy, cone-beam CT, PET, PET / CT, MRI, optics, ultrasound, image fusion, and / or image flow, to support the procedure and / or usage environment, including physical / mechanical interoperability (e.g., interoperability within a cone-beam CT workspace for collecting imaging data before, during, and / or after tissue lithotripsy), and to provide access to and display of patient medical data, including but not limited to examination data and historical medical record data.

[0053]

[0059] Depending on the embodiment, one or more carts may be configured to work in conjunction. For example, one cart may include a bedside mobile cart equipped with a therapeutic transducer and one or more robotic arms usable with therapeutic generators / amplifiers, etc., while an accompanying cart, located away from the patient and working in conjunction with it, may include built-in imaging and a console / display for controlling the robot and the treatment surface, similar to a surgical robot and master / slave configuration.

[0054]

[0060] Depending on the embodiment, the system may include multiple carts, each being a slave to a single master cart and equipped to perform acoustic cavitation procedures. Depending on the configuration and potential configuration, one cart configuration may reduce operating room congestion by allowing the storage of specific subsystems at a certain distance, while another linked cart may essentially include bedside subsystems and components (e.g., delivery systems and treatment components).

[0055]

[0061] Many substitutions and configurations of the cart design can be conceived, and these embodiments do not limit the scope of this disclosure.

[0056] Tissue disruption

[0062] Tissue disruption involves short, high-amplitude focused ultrasonic pulses to generate a dense, powerful “bubble cloud” capable of targeted fragmentation and destruction of tissue. When directed towards tissue interfaces, including tissue / fluid interfaces, tissue disruption can produce controlled tissue erosion, and when bulk tissue is targeted, it can produce clearly defined tissue fragmentation and destruction at the subcellular level. Unlike other forms of ablation, including thermal and radiation modalities, tissue disruption does not rely on heat or ionizing (high) energy for tissue treatment. Instead, tissue disruption uses acoustic cavitation generated at the focus to mechanically act on the tissue structure, and in some cases liquefy, suspend, solubilize, and / or destroy the tissue into subcellular components.

[0057]

[0063] Histotripsy can be applied in various forms, including: 1) Intrinsic-Threshold Histotripsy: A pulse of 1 to 2 cycles with high amplitude negative / tensile phase pressure (e.g., approximately 24-28 MPa for aqueous soft tissue) exceeding the intrinsic threshold is delivered to induce cavitation in the medium; 2) Shock-Scattering Histotripsy: A pulse typically lasting 3 to 20 cycles is delivered. Shock waves (positive / compression phase) scattered from the initial individual microbubbles form inverse shock waves, which constructively interfere with the incident negative / tensile phase to form a high amplitude negative / dilute phase exceeding the intrinsic threshold. In this way, clusters of cavitating microbubbles are produced. The amplitude of the tensile phase of the pulse is sufficient to generate bubble nuclei in the medium so that they undergo inertial cavitation within the focal region throughout the pulse duration. These nuclei scatter the incident shock wave, constructively interfering with it so that the incident shock wave inverts and exceeds the threshold for intrinsic nucleation. 3) Boiling Histotripsy: This employs pulses with a duration of approximately 1 ms to 20 ms. The absorption of the shock pulse rapidly heats the medium, thereby lowering the threshold for intrinsic nucleation. When this intrinsic threshold coincides with the peak negative pressure of the incident wave, boiling bubbles are formed at the focus.

[0058]

[0064] The high pressure generated at the focal point causes a cloud of acoustic cavitation bubbles to form above a certain threshold, thereby generating localized stress and strain within the tissue and mechanical fracture without significant thermal welding. At pressure levels where cavitation does not occur, minimal effects are observed on the tissue at the focal point. This cavitation effect is observed only at peak negative pressures of approximately 10 MPa to 30 MPa, which are significantly higher than the pressure level that defines the inertial cavitation threshold in water for a similar pulse duration.

[0059]

[0065] Tissue fragmentation can be performed in multiple ways and with different parameters. It can be performed completely non-invasively by acoustically coupling a focused ultrasound transducer to the patient's skin and percutaneously delivering acoustic pulses through the covering (and intervening) tissue to a focal area (treatment area and site). The applications of tissue fragmentation are not limited to percutaneous techniques and are applicable by any means that allows contact between the tissue and the transducer, including open surgery, laparoscopic surgery, and percutaneous and robotic surgical procedures. If the resulting bubble cloud is observable, for example, as a highly dynamic echogenic region on a B-mode ultrasound image, and continuous visualization is possible through its use (and associated procedures), tissue fragmentation can be further targeted, planned, directed, and observed under direct visualization by ultrasound imaging. Similarly, treated and fragmented tissue exhibits dynamic changes (typically a decrease) in echogenicity, which can be used to evaluate, plan, observe, and monitor the treatment.

[0060]

[0066] Generally, in tissue disruption therapy, an ultrasonic pulse of one or more acoustic cycles is applied, and bubble cloud formation depends on the pressure release scattering (sometimes exceeding 100 MPa, P+) of the positive shock wavefront from the initially generated, sparsely distributed bubbles (or a single bubble). This is called the "shock scattering mechanism."

[0061]

[0067] This mechanism relies on one (or several sparsely dispersed) bubble generated in the initial negative half-cycle of the pulse at the transducer's focus. Next, a cloud of microbubbles is formed due to pressure-releasing backscattering of the high-peak positive shock wavefront from these sparsely generated bubbles. These backscattered high-amplitude rarefied waves exceed the intrinsic threshold, thus generating a localized, high-density bubble cloud. Then, each subsequent acoustic cycle causes further cavitation due to backscattering from the bubble cloud surface growing toward the transducer. As a result, an elongated, high-density bubble cloud is observed growing along the acoustic axis opposite to the direction of ultrasonic propagation, due to the shock scattering mechanism. This shock scattering process makes bubble cloud generation dependent not only on the peak negative pressure but also on the number of acoustic cycles and the amplitude of the positive shock. In the absence of at least one strong shock wavefront generated by nonlinear propagation, a high-density bubble cloud is not generated when the peak negative half-cycle falls below the intrinsic threshold.

[0062]

[0068] When ultrasonic pulses of less than two cycles are applied, shock scattering can be minimized, and the formation of a high-density bubble cloud depends on the negative half-cycle of the applied ultrasonic pulse exceeding the "intrinsic threshold" of the medium. This is called the "intrinsic threshold mechanism."

[0063]

[0069] This threshold can range from 26 MPa to 30 MPa for soft tissues with high water content, such as soft tissues in the human body. Depending on the embodiment, this intrinsic threshold mechanism can be used to make the spatial extent of damage clearer and more predictable. At peak negative pressures (P-) not significantly higher than this threshold, reproducible damage of only a few subwavelengths, about half the transducer's -6 dB beamwidth, may occur.

[0064]

[0070] With high-frequency tissue disruption pulses, the minimum reproducible injury size is smaller, which is advantageous in applications requiring precise injury generation. However, high-frequency pulses are more susceptible to attenuation and distortion, making them problematic treatments at deeper penetration depths (e.g., ablation in deep tissues) or through distorting media (e.g., transcranial procedures or procedures where pulses are delivered through bone). Tissue disruption can also be applied as low-frequency "pump" pulses (typically <2 cycles and having frequencies between 100 kHz and 1 MHz) along with high-frequency "probe" pulses (typically <2 cycles and having frequencies above 2 MHz or in the range between 2 MHz and 10 MHz), in which case the peak negative pressures of the low-frequency and high-frequency pulses constructively interfere to exceed an intrinsic threshold in the target tissue or medium. Low-frequency pulses, which are more resistant to attenuation and distortion, can increase the peak negative pressure (P-) level relative to the region of interest (ROI), while high-frequency pulses, which offer greater precision, can pinpoint the target site within the ROI and increase the peak negative pressure (P-) beyond the intrinsic threshold. This technique is sometimes called "dual-frequency," "dual-beam tissue disruption," or "parametric tissue disruption."

[0065]

[0071] Additional systems, methods, and parameters for performing optimized tissue disruption using impact scattering, an intrinsic threshold, and various parameters enabling frequency synthesis and bubble manipulation are included herein as part of the systems and methods disclosed herein. These include additional means for controlling the tissue disruption effects described above with respect to the steering and positioning of the focus, and simultaneously managing tissue effects (e.g., pre-focusing thermal injury) at the treatment site or within intervening tissue. Also disclosed are various systems and methods that may include, but are not limited to, multiple parameters, including, frequency, operating frequency, center frequency, pulse repetition frequency, pulse, burst, number of pulses, cycle, pulse length, pulse amplitude, pulse duration, delay, burst repetition frequency, sets thereof, loops of multiple sets, loops of multiple and / or different sets, sets of loops, and various combinations or substitutions thereof. These are included herein as part of the disclosure, including embodiments of these that may be conceived in the future.

[0066] Therapeutic components

[0072] The therapeutic subsystem may work in conjunction with other subsystems for generating, optimizing, implementing, visualizing, monitoring, and controlling acoustic cavitation, also referred to herein and hereafter as “tissue disruption,” and its derivatives, including boiling tissue disruption and other thermal high-frequency ultrasonic techniques. It should be noted that the inventions of this disclosure may also be more beneficial to other acoustic therapies that do not involve cavitation, mechanical, or tissue disruption components. The therapeutic subsystem may include, among other mechanisms, an ultrasonic therapeutic transducer and pulse generator system configured to deliver ultrasound into tissue.

[0067]

[0073] To produce and carry out tissue disruption and its derivatives, the therapeutic subsystem may include, but is not limited to, one or more function generators, amplifiers, therapeutic transducers, and power supplies.

[0068]

[0074] A therapeutic transducer may comprise a single or multiple elements configured to be excited by high-amplitude electrical pulses (>1000V or any other voltage capable of causing tissue damage). The amplitude required to drive the therapeutic transducer for tissue destruction varies depending on the transducer design and the materials used (e.g., solid or polymer / piezoelectric composites, including ceramic or single crystals) and the transducer center frequency, which is directly proportional to the thickness of the piezoelectric material. Thus, a transducer operating at high frequencies requires a lower voltage to produce a given surface pressure than a low-frequency therapeutic transducer. In some embodiments, the transducer element is formed using a piezoelectric polymer composite or a solid piezoelectric material. The piezoelectric material may also be polycrystalline / ceramic or single-crystal in structure. In some embodiments, the transducer element can be formed using silicon, including CMUT and PMUT designs, using MEMS technology.

[0069]

[0075] Depending on the embodiment, the function generator may include a field-programmable gate array (FPGA) or other suitable function generator. The FPGA can be configured using the parameters disclosed above herein, which include, but are not limited to, frequency, pulse repetition frequency, burst, number of bursts which may include pulses, number of pulses, pulse length, pulse duration, delay, burst repetition frequency or duration, where the set of bursts may include a set of parameters, the loop set may include various sets of parameters, with or without delay, or with different delays, with different time delays, and it is possible to repeat and / or introduce new loop sets that are independently controlled, and various combinations and substitutions of these are possible throughout.

[0070]

[0076] In some embodiments, the generator or amplifier may be configured to serve as a general-purpose single-cycle or multi-cycle pulse generator, accommodating Class D drive or inductive drive, and to serve any further conceivable clinical applications and operating environments, some of which are described later in this disclosure. In other embodiments, the Class D or inductive current driver may be configured to include a transformer and / or autotransformer drive circuit to further provide an increasing / decreasing component, and more optionally, preferably to enable amplitude increasing. The generator or amplifier may also include certain protective mechanisms to further support the system and to provide protection for other components of the system (e.g., therapeutic transducers and / or amplifier circuit components) and / or the user from a variety of hazards, including but not limited to electrical safety hazards, that could cause harm, injury, or problems to the operating environment, the system and the therapeutic system, and the user.

[0071]

[0077] The disclosed generator may enable and support the following: the ability of the system (via available software tools) to select, change and control a variety of parameters, including but not limited to those disclosed above; the ability to start / stop treatment; set and read voltage levels, pulse and / or burst repetition frequencies, cycle count, duty cycle, available channels and delays, etc.; modulate pulse amplitude on a fast time scale independent of the high voltage source; and / or other service, diagnostic or therapeutic functions.

[0072]

[0078] Depending on the embodiment, the therapeutic subsystem and / or its components, such as amplifiers, may further include embedded computer processing functions, be networked, connected, accessible, and / or removable / portable, modular, and / or interchangeable between systems, and / or be driven / directed by / from other systems, or in various combinations. Other systems include other acoustic cavitation / tissue disruption, HIFU, HITU, radiotherapy, radiofrequency, microwave and cryoablation systems, navigation and positioning systems, open surgery, laparoscopy, single-incision / single-port, endoscopic and non-invasive surgical robots, laparoscopic towers or surgical towers including other energy-based or viewing systems, surgical system racks or booms, imaging carts, and the like.

[0073]

[0079] Depending on the embodiment, one or more amplifiers may include a Class D amplifier and associated drive circuitry including matching circuitry components. Depending on the selection of the transducer element electrical impedance and the matching circuitry components (e.g., an LC circuit consisting of a series inductor L1 and a parallel capacitor C1), the combined impedance can be set aggressively low to have the high-amplitude electrical waveform required to drive the transducer element. The maximum amplitude of the Class D amplifier depends on the circuitry components used, including the drive MOSFET / IGBT transistor, matching circuitry components or inductor, and transformers or autotransformers, and can typically be in the low kV range (e.g., 1kV to 3kV).

[0074]

[0080] The therapeutic transducer element is excited by an electrical waveform with an amplitude (voltage) that generates sufficient pressure output for tissue disruption therapy. The excitation field can be defined as the required waveform voltage depending on the thickness of the piezoelectric element. For example, a piezoelectric element operating with a 1 MHz transducer is half the thickness of an equivalent 500 kHz element, so the voltage required to achieve the same field and surface pressure is halved.

[0075]

[0081] The therapeutic subsystem may also include therapeutic transducers with various designs and operating parameters to accommodate use in various procedures (and procedures). The system may be configured with one or more therapeutic transducers that are further compatible and interoperable with various embodiments of similar or different systems (for example, it may interface with a robotic arm using a common interface and exchange mechanism, or conversely, it may be adapted to interoperate in a different manner with application-specific imaging probes, in which case different imaging probes may interface with and integrate with therapeutic transducers in distinctly different manners).

[0076]

[0082] Therapeutic transducers can be comprised of various parameters, including size, shape (e.g., rectangular or circular, anatomically curved housing), geometry, focal length, number of elements, element size, element distribution (e.g., number of rings and ring size in annular patterning transducers), frequency, and available electron beam steering. Transducers can be comprised of various materials (e.g., piezoelectric, silicon), form factors and types (e.g., machined components, chip bases), and / or various manufacturing methods.

[0077]

[0083] Transducers can be designed and optimized for clinical applications (e.g., abdominal tumors, peripheral vascular disorders, fat ablation, etc.) and desired outcomes (e.g., acoustic cavitation / tissue disruption without thermal damage to intervening tissues), offering a broad operating range including relatively shallow and surface targets (e.g., thyroid nodules or mammary nodules) and deeper or hard-to-reach targets such as central liver tumors or brain tumors. Transducers can be configured to enable acoustic cavitation / tissue disruption under various parameters and sets made available by the aforementioned system components (e.g., function generators and amplifiers, etc.), including but not limited to frequency, pulse repetition rate, pulses, pulse count, pulse length, pulse duration, delay, repetition, synchronization delay, synchronization duration, synchronization pulse, synchronization pulse delay, various loop sets, and others and substitutions thereof. Transducers can also be designed to enable activation of drug payloads accumulated in tissue by various means, including injection, implantation, or delivery of micelles or nanostructures. Embedded imaging

[0078]

[0084] The system of this disclosure may include various imaging modalities that enable the user to visualize, monitor, and collect / use feedback from the patient's biostructure, relevant areas of interest and treatment / procedure site, and surrounding and intervening tissues, in order to evaluate, plan, perform, and adjust treatment parameters as necessary. The imaging modalities may include various ultrasound, X-ray, CT, MRI, PET, fluoroscopy, optics, contrast or contrast agent types, and / or various combinations thereof. It is further disclosed that various image processing and characterization techniques are also available to enable enhanced visualization and user decision-making. These may be selected or commanded manually by the user or automatically by the system. The system may be configured to enable juxtaposition, toggle, superposition, 3D reproduction, segmentation, alignment, multimodal image fusion, image flow, and / or any other method, enabling the user to identify, define, and be notified of various aspects of using imaging displayed on various system user interfaces and displays during a procedure. Examples, in a non-limiting manner, may include the localization, visualization, and characterization of possible treatment sites within, on, and / or around an area of ​​interest, organ systems, organs or tissues, important structures such as glands, blood vessels, nerves, ureters, fissures, sacs, tumors, tissue damage / injury / disease, other organs, connective tissue, and / or the identification of one or more of these relative to each other (e.g., tumor drainage lymph nodes or blood vessels, or tumors near organ sacs or other underlying organs).

[0079]

[0085] The system can be configured to include onboard embedded imaging hardware, software, sensors, probes, and wetware, and / or to communicate with and interface with external imaging and image processing systems. These components can also be incorporated into the system's therapeutic subsystem components, in which case probes, imaging arrays, etc., are electrically, mechanically, or electromechanically integrated into the therapeutic transducer. This can partially provide the capability to have geometrically aligned imaging and treatment, possibly along the imaging, with the treatment directly in the field of view. In some embodiments, this integration may include a fixed orientation of the imaging function (e.g., imaging probe) in relation to the therapeutic transducer. In other embodiments, the imaging product may be able to move or adjust its own position, including modification of angle, extension (e.g., distance from the therapeutic transducer or patient), rotation (e.g., imaging plane in the example of an ultrasound probe), and / or other parameters, including dynamic movement / adjustment while actively imaging. The imaging component or probe can be encoded so that its orientation and position can be determined relative to another aspect of the system, such as the therapeutic transducer and / or a robot-responsive positioning component.

[0080]

[0086] In one embodiment, the system may include an onboard ultrasound mechanism further configured to allow the user to visualize, monitor, and receive feedback on the treatment site via a system display and software, which includes enabling ultrasound imaging and characterization (and various forms thereof), ultrasound-guided planning, and ultrasound-guided treatment, all in real time. The system may be configured to allow the user to image the patient manually, semi-automated, or fully automated (e.g., using a hand or robot-compatible imaging device).

[0081]

[0087] Depending on the embodiment, imaging feedback and monitoring may include monitoring changes in backscattering from bubble clouds, speckle reduction in backscattering, backscattering speckle statistics, tissue dynamic properties (i.e., elastography), tissue perfusion (i.e., ultrasound contrast), shear wave propagation, acoustic emissions, electrical impedance tomography, and / or various combinations thereof, including visualization by other forms of imaging (e.g., CT or MRI) or integration with other forms of imaging.

[0082]

[0088] Depending on the embodiment, imaging including feedback and monitoring from backscatter from bubble clouds can be used as a method to immediately determine whether a tissue disruption process has been initiated, properly maintained, or stopped. For example, this method allows for real-time, continuous monitoring of drug delivery, tissue erosion, etc. The method can also provide feedback that allows for initiating the tissue disruption process at a higher intensity and maintaining it at a significantly lower intensity. For example, backscatter feedback can be monitored by any transducer or ultrasound imaging device. By measuring feedback from a therapeutic transducer, an auxiliary transducer may be configured to send a call pulse or passively detect cavitation. Furthermore, the nature of the received feedback can be used to adjust acoustic parameters (and associated system parameters) to optimize drug delivery and / or tissue erosion processes.

[0083]

[0089] Depending on the embodiment, imaging including feedback and monitoring from backscatter and speckle reduction may be configured in the system.

[0084]

[0090] In systems that include backscattering feedback and monitoring, and as background information, as the tissue is gradually mechanically subdivided, in other words homogenized, fragmented, or eroded, the size and dispersion of acoustic scattering change as a result of this process. At some point in this process, the scattering particle size and density are reduced to a level where ultrasound is hardly scattered, or the amount of scattering decreases significantly. As a result, the coherent illumination source, in this case speckle, which is the coherent constructive and canceling interference pattern of light and dark spots seen on the image when ultrasound is used, is significantly reduced. After a certain amount of treatment time, dark areas appear within the treatment volume as a result of the speckle reduction. The amount of speckle reduction is related to the amount of tissue subdivision and can therefore be related to the size of the remaining tissue fragments. When this size is reduced to a subcellular level, it is considered that there are no remaining cells. Thus, treatment can proceed until the desired level of speckle reduction is reached. Speckle is readily observed and evaluated on standard ultrasound imaging systems. Dedicated transducers and systems, including those described herein, are also available to evaluate changes in backscattering.

[0085]

[0091] Furthermore, in systems that include speckle-based feedback and monitoring, and as background information, images may persist between frames with minimal change, provided the scattering distribution remains unchanged and there is no movement of the subject. However, scattering can change sufficiently to be detected by signal processing and other means well before the magnitude of the scattering is reduced enough to cause a speckle reduction. Techniques in this lineage can function as detectors of changes in speckle statistics. For example, the correlation between the magnitude and location of one or more specks in an image begins to be lost before an observable speckle reduction occurs. Speckle uncorrelatedness, after appropriate motion correction, can become a highly sensitive metric for mechanical tissue disruption and, therefore, a metric for therapeutic effectiveness. This feedback and monitoring technique allows for early observation of changes resulting from the acoustic cavitation / tissue disruption process, enabling the identification of changes in tissue before significant or complete tissue effects (e.g., the occurrence of erosion). In one embodiment, this method may be used to monitor the acoustic cavitation / tissue disruption process for advanced drug delivery, where the treatment site / tissue is disrupted over time and tissue damage / erosion is undesirable. In other embodiments, this may include speckle-free scattering due to the motion of scattering in the gradually fluidizing treatment volume, for example, when partial or complete tissue erosion is desired.

[0086]

[0092] In systems that include elastography-based feedback and monitoring, and as background information, when the treatment site / tissue is further subdivided (homogenized, fragmented, or eroded) by acoustic cavitation / tissue fragmentation effects, its mechanical properties change from a soft but interconnected solid to a viscous fluid or paste with little long-range interaction. Such changes in mechanical properties can be measured by various imaging modalities, including MRI and ultrasound imaging systems. For example, ultrasound pulses can be used to generate a force (i.e., radiation pressure) on a localized volume of tissue. This tissue response (displacement, strain, and velocity) can change significantly during tissue fragmentation therapy, allowing the state of tissue fragmentation to be determined by imaging or other quantitative means.

[0087]

[0093] The system may also include feedback and monitoring based on changes in shear wave propagation. As background information, tissue fragmentation makes the tissue more fluid and less solid, and fluid systems generally do not propagate shear waves. Therefore, the degree of tissue fluidization provides opportunities for feedback and monitoring of the tissue disruption process. For example, ultrasound and MRI imaging systems can be used to observe shear wave propagation. The disappearance of such waves in the treatment volume is used as a criterion for measuring tissue damage or disruption. In one embodiment of the system, the system and support subsystems can be used to generate and measure interacting shear waves. For example, two adjacent ultrasound foci may perturb the tissue by pushing it in a particular way. If the adjacent foci are in a fluid, there are no shear waves propagating to interact with each other. If the tissue is not fluidized, interaction will be detected using external means, for example, by different frequencies that are only detected if two shear waves interact nonlinearly, their disappearance correlating with tissue damage. Therefore, the system may be configured to use this modality to enhance feedback and monitoring of acoustic cavitation / tissue disruption procedures.

[0088]

[0094] In systems that include feedback and monitoring via acoustic emissions, and as background information, as tissue volume is subdivided, its effect on acoustic cavitation / tissue disruption (e.g., bubble clouds in this case) changes. For example, bubbles may grow larger, have different lifespans, collapse, and change their properties in intact and fluidized tissue. Bubbles can move and interact even after tissue subdivision, resulting in larger bubbles or synergistic interactions between bubbles, and as a result of all this, acoustic emissions change. Such emissions can be heard during treatment and change during treatment. Analysis of such changes and their correlation with treatment effects can enable monitoring of treatment progress and may be configured as a function of the system.

[0089]

[0095] In systems that include feedback and monitoring via electrical impedance tomography, and as background information, an impedance map of the treatment site can be created based on the spatial electrical properties of the entire treatment site. By performing electrical measurements on the skin surface, imaging of the conductivity or dielectric constant of the patient's treatment site can be estimated. Conductive electrodes are attached to the patient's skin, and a small alternating current is applied to some or all of the electrodes. One or more known currents are injected into this surface, and voltages are measured at multiple points using the electrodes. This process can be repeated for different settings of applied current. The resolution of the resulting image can be adjusted by changing the number of electrodes employed. From the impedance map, measurements of the electrical properties of the treatment site within the skin surface can be obtained, and depending on the configuration of the system and support subsystems, this can be used to monitor changes and locations of acoustic cavitation / tissue disruption (e.g., specifically bubble clouds) and the tissue disruption process.

[0090]

[0096] The user may also be able to select, annotate, mark, highlight, and / or contour various regions of interest or treatment sites (on the image) and defined treatment targets, which can be used to command and direct the system, via system software, user interface, and display, to where to acquire, examine, and / or treat. Depending on the configuration, the user may use a manual ultrasound probe (e.g., a handheld diagnostic probe) to perform the procedure. In another configuration, the system may use a robotic and / or electromechanical positioning system to perform the directed and / or system-automated procedure, or conversely, the system may allow a combination of manual and automated use.

[0091]

[0097] The system may further include the ability to perform image registration, including imaging and image dataset alignment to enable the system's navigation and localization to a patient, including the identification of a treatment site (e.g., tumor, vital structure, anatomical bone structure, anatomical structure and its features). In one embodiment, the system enables a user to image and identify a region of interest, e.g., the liver, using built-in ultrasound, and to select and mark a tumor (or its surrogate marker) contained within the liver via / displayed in the system software, the system then aligns the image data to a coordinate system defined by the system, further enabling the system's therapeutic and robotic subsystems to perform synchronized acoustic cavitation / tissue disruption on the marked tumor. The system may further include the ability to align various image sets, including those disclosed above, with each other, and to provide navigation and localization (e.g., of the therapeutic transducer to the images by tracking the therapeutic transducer and robotic subsystem to the CT or MRI / ultrasound fusion images).

[0092]

[0098] The system may also include the ability to operate in a variety of intervention, endoscopic, and surgical environments, including standalone operation and operation in conjunction with other systems (surgical / laparoscopic towers, visual systems, endoscopic systems and towers, ultrasound-enabled endoscopic ultrasound (flexible and rigid), percutaneous / endoscopic / laparoscopic and minimally invasive navigation systems (e.g., optical, electromagnetic, shape detection, ultrasound-enabled, etc.)), which may also be linked to or include various optical imaging capabilities (e.g., fiber and / or digital). The system of this disclosure is configurable to link with these systems, and in some embodiments may be juxtaposed and linked with them, or in other embodiments, all or part of the system (e.g., acoustic cavitation / tissue disruption-enabled endoscopic system or laparoscopic surgical robot) may be incorporated into the above system / platform. In many of these environments, for example, during or before / after use of optically guided endoscopes / bronchoscopes, or as another embodiment, a laparoscopic robot (e.g., Intuitive Da Therapeutic transducers can be used when the Vinch*Xi system is observing / manipulating the tissue / treatment site. These environments and embodiments may also include cases where the other systems / platforms described above are used to deliver fluid (locally) to enable the creation of an artificial acoustic window that would not normally exist (e.g., fluidizing a section or lobe of the lung in preparation for acoustic cavitation / tissue disruption by non-invasive transthoracic treatment) (e.g., transducers positioned externally on / around the patient). The systems disclosed herein may also include all or part of their subsystem hardware packaged within the other system carts / consoles / systems described herein (e.g., acoustic cavitation / tissue disruption systems and / or subsystems incorporated and operated from the navigation or laparoscopy systems described above).

[0093]

[0099] The system can also be configured to spatiotemporarily display real-time visualizations of bubble clouds, including tissue effects of intra- and post-treatment outcomes due to tissue / bubble cloud interactions, using various parameters as described above and other parameters. In this configuration, the system can dynamically image, visualize, and display the bubble clouds and their changes (e.g., decrease and increase in echo intensity), which may include intensity, shape, size, location, form, and persistence. These features may allow users to track and follow treatments continuously in real time within a single integrated procedure and interface / system, enabling immediate confirmation of the safety and effectiveness of the treatment (in contrast to other interventions or surgical modalities that require multiple procedures to achieve the same thing, or where treatment effects cannot be seen in real time (e.g., radiotherapy), or where such a thing is impossible (e.g., real-time visualization of local tissue during thermal ablation), and / or other procedures that require further invasive techniques (e.g., incision or puncture) and repeated imaging (CT or MRI scanning) in the scanner between procedure steps). The systems, subsystems, components, modalities, mechanisms, and workflows / usages described above can be implemented in an unrestricted manner by making the hardware, software, user interfaces, and usage environments available, and any future improvements, enhancements, and inventions in this art, along with the resulting data and the means of using that data for analytical, artificial intelligence, or digital health applications and systems, are deemed to be included within the scope of this disclosure.

[0094] robot

[0100] The system may include a variety of robotic subsystems and components, including, but not limited to, one or more robotic arms and controllers, which may further cooperate with other subsystems or components of the system to perform and monitor acoustic cavitation / tissue disruption. As described herein, the robotic arms and control systems may be incorporated into one or more cart configurations.

[0095]

[0101] For example, one embodiment of the system may include a cart equipped with a built-in robotic arm and control system, and treatment, built-in imaging, and software, wherein the robotic arm and other enumerated subsystems are controlled by the user in the form factor of a single bedside cart.

[0096]

[0102] In other embodiments, the robot subsystem may consist of one or more separate carts that can be driven in a master / slave configuration from a separate master or cart, in which case the robot-enabled cart is located next to the bed / patient and the master is located at a distance from the cart.

[0097]

[0103] The disclosed robotic arm may consist of multiple joints, compartments, and degrees of freedom, and may also include various types of embedded sensors and encoders implemented for various uses and safety functions. Sensing techniques and data may include, as an example, vision, potentiometers, position / location, motion, force, torque, velocity, acceleration, and / or dynamic loading. In some cases, sensors may be used to instruct the robot with commands (e.g., hand gestures to place the robot in a preferred setup position or to retract it into a fixed position). Further details relating to the robotic arm are described in Kassow et al., U.S. Patent Publication 2013 / 0255426, which is disclosed in its entirety herein by reference.

[0098]

[0104] The robotic arm receives control signals and commands from a robotic control system housed in a cart. The system can be configured to provide a variety of functions, including but not limited to position, tracking, pattern, triggering, and event / action.

[0099]

[0105] The positions may be configured to include fixed positions, pallet positions, time-controlled positions, distance-controlled positions, variable time-controlled positions, and variable distance-controlled positions.

[0100]

[0106] Tracking may be configured to include time-controlled tracking and / or distance-controlled tracking.

[0101]

[0107] The movement pattern may be configured to include an intermediate position or midpoint and a series of positions along a defined path in space.

[0102]

[0108] The trigger may be configured to include, but is not limited to, distance measuring means, time, and / or various sensor means, including visual / imaging, force, torque, localization, energy / power feedback, and / or others, as disclosed herein.

[0103]

[0109] Events / actions may be configured to include a variety of examples, such as proximity methods (approaching / moving away from a target), activation or deactivation of various end-effectors (e.g., therapeutic transducers), start / stop / interruption sequences of the above events, triggers or toggles of triggers for events / actions, initiation of movement patterns, changes / toggles between movement patterns, and / or time-based or temporal events / actions that span defined tasks and spatiotemporal periods.

[0104]

[0110] In one embodiment, the system includes a three-degree-of-freedom robot positioning system that allows the user to perform micropositioning of the therapeutic transducer in X, Y, and Z coordinate systems (via the system's software and associated user interface), while coarse macropositioning of the transducer (e.g., aligning the transducer with the patient's body) is performed manually. In some embodiments, the robot may include six degrees of freedom, including X, Y, Z, and pitch, roll, and yaw. In other embodiments, the robot subsystem may include further degrees of freedom that allow the robot arm support base to be positioned along a linear axis parallel to the approximate direction of the patient plane, and / or allow the height of the support base to be adjusted upward or downward, thereby allowing the position of the robot arm to be modified relative to the patient, patient plane, cart, coupling subsystem, additional robots / robot arms, and / or additional surgical systems, including but not limited to surgical towers, imaging systems, and endoscopic / laparoscopic systems.

[0105]

[0111] One or more robotic arms may also include various mechanisms to assist in manually or semi-manually manipulating and correcting the arm position, which may interface with the therapeutic transducer on or between the furthest joints of the robotic arm. In some embodiments, this mechanism may be configured to include a handle that enables operation and manual control by one or more hands. The handle may also be configured to include a user input and electronic control mechanism for the robotic arm that commands various drive functions or modes (e.g., to activate or deactivate the free-drive mode) to actuate the robot to assist in rough or fine positioning of the arm. A workflow for the initial positioning of the robotic arm and therapeutic head may be configured to allow the therapeutic transducer / head to be first positioned in the binding solution with the therapeutic transducer directly interfaced with the arm, or, in a different workflow, to allow the user to first set up the binding solution, with the robotic arm being able to interface with the therapeutic transducer / binding solution as a later / final setup step.

[0106]

[0112] Depending on the embodiment, the robotic arm may include a laparoscope, single-port, endoscope, a hybrid or combination thereof, and / or other robotic arm, and the robot in the system may be a slave to a master controlling the arm, and may optionally be multiple other arms equipped to perform other tasks (such as visualization, imaging, grasping, cutting, ligation, sealing, closure, stapling, ablation, suturing, marking, etc.) in parallel, including operating one or more laparoscopic arms (and instruments) and various tissue disruption system components. For example, a laparoscopic robot can be used to prepare the surgical site, including manipulating the organ position to provide more ideal acoustic access and optionally further stabilizing the organ to minimize respiratory movement. In conjunction with this, a second robotic arm can be used to perform non-invasive acoustic cavitation through the body cavity, while being observed by simultaneous visualization with a laparoscopic camera under real-time imaging (e.g., ultrasound) from a therapeutic transducer. In other related embodiments, similar techniques may be used in combination with endoscopic and non-invasive techniques, as well as in combination with endoscopy, laparoscopy, and non-invasive techniques.

[0107] software

[0113] The system may include various software applications, mechanisms, and components that enable users to interact with, control, and use the system for a wide range of clinical applications. The software can communicate with and interact with one or more subsystems of the system, including but not limited to therapeutic, embedded imaging, robotics, and other components, auxiliary mechanisms, and accessories.

[0108]

[0114] Overall, without any particular order of importance, the software initializes, sets up, services, communicates / imports / exports / stores data, allows users to change / operate / configure / control / command various settings and parameters, reduces safety and user-related hazards, plans procedures, various configurations of transducers, robotic arms, and drive systems, function generators and amplifier circuits / slaves, test and treatment ultrasound sequences, transducer steering and positioning (electromechanical and electron beam steering, etc.), treatment patterns, support for imaging and imaging probes, their manual and electromechanical / robot movement, and measurement of various dimensions within or around the procedure and treatment site (e.g., depth from one anatomical site to another). Mechanisms and support may be provided to support imaging for determination / characterization analysis, pre-treatment diagnosis and protocols for measurement / characterization analysis of in-situ treatment site characteristics and conditions (e.g., acoustic cavitation / tissue disruption threshold and its heterogeneity), targeting and target registration, calibration, marking / annotation, localization / navigation, registration, guidance, workflow provision and guidance, autonomous execution of procedure steps, treatment plans and protocols, autonomous execution with direct observation and visual monitoring using real-time imaging according to software display including various fields of view and observation viewpoints for autonomous and visual monitoring, communication tools (video, audio, sharing, etc.), troubleshooting, instructions, warnings, alarms, and / or communication via various networking devices and protocols.Furthermore, it is conceivable that the software user interface and support display may include a variety of buttons, commands, icons, graphics, text, etc., enabling the user to interact with the system in a user-friendly and effective manner, and that these may be presented in an unlimited number of substitutions, layouts, and designs, and may include multiple displays (e.g., touchscreen monitors and touchpads), and / or may be displayed in a similar or different set of mechanisms for the system, and may be networkable with one or more external displays or systems (e.g., another robot, navigation system, system tower, console, monitor, touch display, mobile device, tablet, etc.).

[0109]

[0115] The software may support various function generators (e.g., FPGAs), amplifiers, power supplies, and therapeutic transducers as part of a typical system including one or more computer processors. The software may be configured to allow the user to select, determine, and monitor various parameters and settings for acoustic cavitation / tissue disruption, and to allow the user to stop / start / modify the above parameters and settings upon observation / receiving feedback regarding performance and status.

[0110]

[0116] The software may be configured to allow the user to select from a list or menu of multiple transducers and to support automatic detection of the transducers (and verification of appropriate sequence and parameter settings based on the selected application) once the transducers are connected to the system. In other embodiments, the software may update targeting and amplifier settings (e.g., channels) based on a specific transducer selection. The software may also provide transducer recommendations based on pre-treatment and planning inputs. Conversely, the software may give the user an error message or warning if the selection or parameters of the treatment transducers, amplifiers, and / or function generators are incorrect, faulty, or cause injury. This may further include reporting the details and location of the error.

[0111]

[0117] In addition to the above, the software may be configured to allow the user to select treatment sequences and protocols from a list or menu, and to remember selected and / or previously selected sequences and protocols, associating them with specific clinical use or patient profiles. Associated profiles may include any associated patient, procedure, clinical data and / or technical data, and may be used to notify, modify and / or guide current or future treatments or procedures / interventions, whether as decision support or as an active part of the procedure itself (e.g., using serial datasets to build and guide new treatments).

[0112]

[0118] As part of the plan or during treatment, the software (in conjunction with other components of the system) may allow the user to evaluate and test acoustic cavitation / tissue disruption thresholds at various locations within a user-selected region of interest or a defined treatment area / volume, in order to determine a minimum cavitation threshold for the entire region or volume, so as to ensure that treatment parameters are optimized to achieve, maintain, and dynamically control acoustic cavitation / tissue disruption. In one embodiment, the system may allow the user to manually evaluate and test threshold parameters at various points. These points may include defined boundaries of the selected region of interest and treatment area / volume, points inside the boundaries, and points at the center of the site / location, and the resulting threshold measurements may be reported / displayed to the user and used to update treatment parameters before treatment. In another embodiment, the system may be configured to enable automated threshold measurement and updating, which is made available by the robot subsystem described above, in which case the user may instruct the robot or the robot may be commanded to perform the measurements autonomously.

[0113]

[0119] The software may be configured to enable various substitutions for performing and positioning optimized acoustic cavitation / tissue disruption across a selected range / volume by coordinating with a computer processor and one or more function generators, amplifiers, and therapeutic transducers. This may include, but is not limited to, systems configured with various combinations of these, including fixed / natural focus placement using purely electromechanical positioning configurations, electron beam steering (with or without electromechanical positioning), electron beam steering to a newly selected fixed focus with further electromechanical positioning, axial (Z-axis) electron beam steering with lateral (X and Y) electromechanical positioning, high-speed axial electron beam steering with lateral electromechanical positioning, high-speed beam steering in 3D space, and dynamic modification of one or more acoustic cavitation / tissue disruption parameters based on the above-mentioned functions that update therapeutic parameters based on threshold measurements (e.g., dynamic adjustment of amplitude across the entire therapeutic range / volume). Other components, auxiliary mechanisms, and accessories

[0114]

[0120] The system may include, but is not limited to, computers, computer processors, power supplies including high-voltage power supplies, controllers, cables, connectors, network devices, security, communications, software applications for integration into information systems including hospital information systems, cellular communication devices and modems, handheld wired or wireless controllers, high-visualization goggles or glasses, augmented reality or virtual reality applications, cameras, sensors, tablets, smart devices, telephones, Internet-enabled functions of objects, special-purpose "apps" or user training materials and applications (software or paper-based), virtual proctors or trainers, and / or other corresponding mechanisms, devices, systems or applications, and / or methods of using the foregoing, as well as various other components, auxiliary mechanisms and accessories. System Modification Modes and Methods / Applications

[0115]

[0121] In addition to performing a wide range of procedures, the system may enable additional benefits such as enhanced planning, imaging, and guidance to assist the user. In one embodiment, the system may allow the user to create patient, target, and application-specific treatment plans, in which case the system may be configured to optimize treatment parameters based on feedback to the system during planning, and the plan may further include the ability to perform various test protocols to collect specific inputs to the system and the plan.

[0116]

[0122] The feedback may include various energy, power, site, location, tissue, and / or other parameters.

[0117]

[0123] The system and the feedback described above can be further configured and used to autonomously (and robotically) execute optimized treatment plans and protocols visualized under real-time imaging during the procedure, thereby allowing the user to directly observe the local therapeutic tissue effect during the course of treatment and to initiate / stop / modify treatment at the user's discretion. Both the trial and treatment protocols can be updated during the procedure, at the user's discretion, or, depending on the embodiment, based on logic incorporated into the system.

[0118]

[0124] Furthermore, it should be understood that many of these advantages can further enhance other forms of acoustic therapy, including thermal ablation using high-intensity focused ultrasound (HIFU) and high-intensity therapeutic ultrasound (HITU), including boiling tissue disruption (thermal cavitation), and are considered part of this disclosure. This disclosure also considers applications of tissue disruption as a means of activating pre-delivered inactive drug payloads whose activity is inactive due to protection in micelles, nanostructures or similar protective structures, or by molecular arrangements that allow activation only when acoustic energy is applied.

[0119]

[0125] In another embodiment, a therapeutic subsystem comprising one or more amplifiers, transducers, and a power supply may be configured to enable multiple acoustic cavitation and tissue disruption drive functions and to provide specific advantages based on application, method, and / or patient-specific use. These advantages include, but are not limited to, the ability to deliver more energy with a more desirable thermal profile, faster treatment speed, and shorter procedure time, and to enable better optimization and control of therapeutic parameters, which may enable electron beam steering and / or other functions.

[0120]

[0126] This disclosure also includes novel systems and concepts relating to systems and subsystems including a novel “general-purpose” amplifier capable of enabling multiple driving methods (e.g., single and multi-cycle pulse supply). Depending on the embodiment, this may include a variety of novel features to further protect the system and user with respect to electrical safety or other hazards (e.g., damage to transducer and / or amplifier circuits).

[0121]

[0127] In another embodiment, the system and treatment subsystem may include many treatment transducers, which are configured for specific applications and uses, capable of accommodating treatments across a wide range of operating parameters (target size, depth, site, etc.) and may include a wide range of operating specifications (detailed below). The transducers can be further adapted, interfaced, and connected to robot-enabled systems and coupling subsystems, allowing the transducers to be placed within or juxtaposed with acoustic coupling devices, thereby enabling simultaneous imaging and tissue disruption therapy through appropriate acoustic windows in many embodiments. Since the tissue effects and bubble clouds of acoustic cavitation / tissue disruption may or may not change in appearance and intensity throughout the treatment, depending on their location within the treatment (e.g., tumor, surrounding healthy tissue, vital structures, adipose tissue, etc.), the treatment transducer may also include an embedded imaging probe or localization sensor capable of displaying and determining the transducer's position within the treatment site and providing a direct view (or representation) of the treatment site.

[0122]

[0128] The systems, methods, and uses of the systems disclosed herein may be beneficial in overcoming unmet needs in the fields of soft tissue ablation, oncology, immuno-oncology, highly image-guided procedures, surgical procedures including but not limited to open, laparoscopic, single incision, natural orifice, endoscopic, non-invasive, and various combinations thereof; various intervention spaces for catheter-based procedures of blood vessels; cardiovascular, pulmonary and / or neurocranial-related spaces; cosmetic / aesthetic, metabolic (e.g., type 2 diabetes), plastic and reconstructive, ophthalmo-ophthalmology, orthopedics, gynecology and men's medicine; and other systems, devices and methods for the treatment of diseased, injured, useless or healthy tissues, organs or cells.

[0123]

[0129] Systems and methods are also provided for improving intratissue treatment patterns, which can shorten treatment time, improve effectiveness, and reduce the amount of energy delivered to the patient and pre-focused tissue heating.

[0124] Usage environment

[0130] The disclosed system, method of use, and use of the system can be implemented in many environments and situations with or without various support systems such as anesthesia, including, but not limited to, treatment rooms, operating rooms, hybrid rooms, inpatient and outpatient facilities, outpatient facilities, imaging centers, radiography, radiotherapy, oncology, surgery and / or any medical center, and clinics, mobile medical centers or systems, automobiles and related vehicles (e.g., vans), air and sea transport means such as aircraft and ships, and / or any structure (e.g., tents) capable of providing temporary therapeutic support. In some cases, the system and / or subsystem disclosed herein may also be provided as an integration mechanism into other environments, e.g., direct integration of the tissue disruption therapy subsystem into an MRI scanner or patient face / bed, in which case at a minimum, a therapy generator and transducer are incorporated therein, and in other cases, the tissue disruption configuration further includes a robotic positioning system, and the robotic positioning system may also be incorporated into the design around the scanner or bed.

[0125] join

[0131] The system may include various coupled subsystem embodiments, which are made available and configured to enable acoustic coupling to the patient (e.g., providing an acoustic window and acoustic medium between the transducer and the patient, and their support) to provide effective acoustic access for ultrasound visualization and acoustic cavitation / tissue disruption. The coupled subsystems may include different form factors of coupled subsystems, including open and closed device solutions and several mechanisms configurable to enable dynamic control of the acoustic medium (e.g., temperature, dissolved gas concentration, particulate filtration level, sterility, volume, composition, etc.). Such dynamic control components may be directly integrated into the system (in the cart) or located in separate external devices and / or the cart, communicating with the system intermittently / intermittently or continuously.

[0126]

[0132] A binding subsystem typically includes, at a minimum, a binding medium (e.g., degassed water or aqueous solution), a storage / container for the binding medium, and a support structure (including interfaces with other surfaces or devices). In most embodiments, the binding medium is water, which may be prepared before or during treatment (e.g., by cooling, degassing, filtering, etc.). A variety of adjustment parameters may be employed based on the system configuration and its intended use / application.

[0127]

[0133] The storage container or medium container may be of various sizes and shapes, and in form and shape to adapt to / conform to the patient, and may be formed and shaped so that the therapeutic transducer can be fitted / accessed and function within the acoustic medium according to defined required working space (minimum volume of the medium that allows the therapeutic transducer to be positioned and / or move through one or more therapeutic positions or patterns, at various distances and depths from the patient, etc.), and the storage container or medium container may also mechanically support the load and load distribution using mechanical and / or electromechanical support structures. Typical examples may include support frames. The container may be of various shapes, sizes, curvatures, and dimensions, and may consist of various material compositions (single, multiple, composite materials, etc.), which may vary throughout. Depending on the embodiment, the container may include mechanisms such as insertable and removable and / or assembled internally, which can be used to conform to the patient and useful for confining / containing the medium within the container. The container may further include various sensors (e.g., volume / fill level), discharge pipes (e.g., inlet / outlet), lights (e.g., LEDs), markings (e.g., filling line, setting orientation, etc.), text (e.g., labels, etc.).

[0128]

[0134] In one embodiment, the storage or medium container houses a sealable frame and a membrane and / or film may be arranged inside it to provide a conformal means of contacting the storage (including later a treatment head / treatment transducer) as an interface with the patient and further providing a barrier to the medium (e.g., water) between the patient and the treatment transducer. In other embodiments, the membrane and / or film may include an opening, the patient-contact edge of which provides a fluid / mechanical seal to the patient, while at the same time allowing direct communication of the medium with the patient (e.g., a direct degassed water interface with the patient). In both of these embodiments, the superstructure of the storage or medium container may further provide a proximal portion (e.g., top) of the open or sealed structure (e.g., for preventing spills or providing additional mechanisms).

[0129]

[0135] The disclosed membranes may consist of various elastomers, viscoelastic polymers, thermoplastics, thermoplastic elastomers, thermosetting polymers, silicones, urethanes, rigid / flexible copolymers, block copolymers, random block copolymers, etc. The materials may be hydrophilic, hydrophobic, surface modified, coated, or extractable, and may also include various additives to enhance performance, appearance, or stability. In some embodiments, the thermoplastic elastomer may be styrene-ethylene-butylene-styrene (SEBS) or other similar strong-flexible elastomers. The form factor of the membrane may be flat or pre-molded before use. In other embodiments, the membrane may be inelastic (e.g., convex) and pressed against the patient's skin to acoustically couple a transducer to tissue. Furthermore, systems and methods for controlling the level of contaminants (e.g., particulate matter) on the membrane to maintain an appropriate level of ultrasonic coupling are disclosed. Too much particulate matter or contaminants may cause ultrasonic scattering. This can be achieved using a removable film or coating on the outer surface of the membrane to protect against contamination.

[0130]

[0136] The above materials can be formed into useful films by molding, integral molding, spraying, ultrasonic spraying, extrusion, and / or any other processing method that produces a useful embodiment. The films can be disposable or reusable. The films may be non-sterilized, aseptically cleaned, or aseptically supplied, and sterilization may include, but is not limited to, any known method including, ethylene oxide, gamma, electron beam, high-pressure steam sterilization, steam, peroxide, plasma, chemical sterilization, etc. The films may be further configured with an externally molded or overmolded frame to provide mechanical stability to the film during handling, including assembly, setting, and disassembly of the coupled subsystem. Various parameters of the film, including thickness, thickness profile, density, and formulation (e.g., high molecular weight and copolymer ratio, additives, plasticizers, etc.), can be optimized for this use, and this typically includes optimization to maximize acoustic transmission properties, including the effect on the cavitation onset threshold and / or ultrasonic imaging artifacts, including, but not limited to, film reflection.

[0131]

[0137] Open storage containers or medium containers may include various filling methods, including the use of a pre-conditioned medium or water that can be supplied into the container according to predetermined specifications of the water (e.g., temperature level and gas saturation rate), or may include additional mechanisms (e.g., ports, valves, hoses, tubes, fittings, bags, pumps, etc.) integrated with the design to enable filling and discharging. These mechanisms may be further configured to be incorporated into or interface with other devices, including, for example, a fluid system. In some cases, the fluid system may be an in-hospital medium conditioning system in a hospital or medical facility room, or differently, a mobile cart-based system that can condition the medium and transfer it to and from the cart to the medium container.

[0132]

[0138] A sealed storage container or medium vessel may include various sealing mechanisms, depending on the embodiment, including sealing to the proximal / upper part or structure of the storage / container, or otherwise, embodiments may include sealing to a transducer or mechanism on the transducer housing. Some embodiments may also include dynamic functions to control the amount of fluid in these designs to minimize the possibility of bubble or turbulence generation in the fluid and to allow changes in the focal length to a target area without moving the transducer. Therefore, built-in mechanisms enabling fluid communication and its control (functions for supplying / removing fluid on demand) may be provided, including functions for monitoring and controlling various fluid parameters, as disclosed above. To provide this functionality, coupled subsystems, both as a whole and as part of the system, may include a fluid conditioning system, which may include various electromechanical devices, systems, power, sensing, computing, pumps, filters, and control systems. The storage container may also be configured to receive signals that deform or change the shape of the container in a specific controlled manner, allowing adjustment of the target point without moving the transducer.

[0133]

[0139] The combined support system may include various mechanical support devices that interface the storage / container and medium with the patient and the workspace (e.g., bed, floor, etc.). Depending on the embodiment, the support system may include a mechanical arm having three or more degrees of freedom. This arm may have a proximity interface with one or more locations (mechanisms) on the bed, including but not limited to frames, rails, customized rails or inserts, and one or more distal locations on the storage or container. The arm may be a mechanism mounted on one or more carts, the carts may consist of various non-limiting substitutional forms, and in some cases the carts may have only the role of supporting and providing the disclosed support structure.

[0134]

[0140] Depending on the embodiment, the support structure and arm may be a robot-responsive arm implemented as a standalone cart or incorporated into a cart further including two or more subsystems, or the robot-responsive arm may be the arm of another robot of intervention, surgery or other types, and may further include various user input mechanisms for operating / controlling (e.g., positioning within / inside the binding medium) the robot arm and / or binding solution mechanism (e.g., filling, discharging, etc.). Depending on the embodiment, a support structure robot arm position encoder may be used to coordinate the operation of a second arm (e.g., including a therapeutic transducer / treatment head), such as to position a therapeutic transducer in a desired / known location and orientation within the binding support structure.

[0135]

[0141] Overall, there are significant unmet needs in interventions and surgical medical procedures, including those using minimally invasive devices and techniques to treat disease and / or injury, and across various types of procedures, and these unmet needs may be addressed by entirely new medical procedures. The functionality of current medical systems is often limited by access, in which case minimally invasive or non-invasive techniques are preferred, or current means cannot achieve the desired / necessary tissue effects (e.g., surgery around / through critical structures without major injury), or the physical configuration of the system makes certain procedure techniques less desirable or impossible, and combinations of techniques, along with enhanced tissue-effect therapies, may enable entirely new procedures and techniques that are currently impossible.

[0136]

[0142] Furthermore, there is a specific need to enable tissue disruption delivery, including robotic tissue disruption delivery, in which one or more tissue disruption therapeutic transducers can be configured to be acoustically connected to the patient, using a completely sealed method (e.g., without acoustic medium communication with the patient's skin), and allowing the one or more tissue disruption transducers to move within the binding solution without interfering with the movement / route of the robotic arm or interfering with / inhibiting the binding interface, which could affect the intended treatment and / or target site.

[0137]

[0143] This specification discloses, in non-limiting examples, tissue lithotripsy acoustic / patient-binding systems and methods that enable tissue lithotripsy therapy / procedures in any setting, including intervention rooms, operating rooms, combined treatment rooms, imaging centers, medical centers, clinics, mobile treatment centers, and / or other situations. The following disclosure further describes novel systems used to fabricate, control, maintain, modify / enhance, monitor, and set up / decommission acoustic / patient-binding systems in a variety of techniques, methods, environments, architectures, and workflows. Generally, the novel systems of this disclosure can have a binding medium, in some embodiments degassed water, serve as the interface between a tissue disruption therapy transducer and a patient, the acoustic medium providing sufficient acoustic coupling to the patient, thereby enabling the delivery of tissue disruption pulses through the user's desired treatment location (and volume), the delivery may require the physical movement of the tissue disruption therapy transducer within a defined workspace containing the binding medium, and the coupling system is configured to allow the free movement of the therapy transducer (and positioning system, e.g., a robot) without obstruction by a coupling support system (e.g., a frame or manifold holding the binding medium).

[0138] Integrated systems and subsystems / components

[0144] The tissue disruption acoustic / patient coupling systems of the present disclosure generally include, but are not limited to, one or more subsystems and components, including, 1) a novel membrane / barrier film providing a sealed conformal patient coupling and tissue disruption system interface; 2) a frame and assembly that holds the membrane and provides sufficient working space and head space for the required range of motion (x, y and z, pitch, roll and yaw) of the disruption therapy transducer; 3) a sufficient amount of ultrasonic medium to provide an interface between the acoustic coupling and the tissue disruption therapy transducer and a robotic arm; 4) one or more mechanical support arms that enable the placement, positioning and load support of the frame, assembly and medium; and 5) a fluid system for preparing, supplying and removing the ultrasonic medium from the frame and assembly.

[0139]

[0145] In some embodiments, the coupling system may be completely sealed, while in other embodiments and configurations, the coupling system may be partially open to allow immediate access (physically and / or visually).

[0140]

[0146] Acoustic / patient coupling systems and subsystems may further include various mechanisms and functions, as well as associated workflows, and can be configured in various ways to enable tissue disruption procedures as detailed below.

[0141]

[0147] Figure 2 shows one embodiment of the lithotripsy and imaging system 200, including the coupling assembly 212. As described above, the lithotripsy and imaging system may include a therapeutic transducer 202, an imaging system 204, a robotic positioning arm 208, and a cart 210.

[0142]

[0148] The therapeutic and / or imaging transducer can be housed within a coupling assembly 212, which may further include a coupling membrane 214 and a membrane constraint mechanism 216 configured to prevent the membrane from expanding excessively far from the transducer. The coupling membrane may be filled with an acoustic coupling medium such as a fluid or gel. The coupling membrane constraint mechanism may be, for example, a semi-rigid or rigid material configured to limit the expansion / movement of the membrane. In some embodiments, the membrane constraint mechanism is not used, and the elasticity and tensile strength of the membrane prevent over-expansion. The coupling membrane may be a mineral oil-mixed SEBS membrane to prevent direct fluid contact with the patient's skin. In the embodiment shown in the figure, the coupling assembly 212 may be load-bearing in the x and y planes but is supported by a mechanical support arm 218 that allows for manual or automatic z-axis adjustment. The mechanical support arm may be mounted on the floor, operating table, or cart 210. The mechanical support arm is designed and configured to hold the binding membrane 214 in contact with the patient's skin and in a predetermined position, while allowing the therapeutic / imaging transducer to be moved by the robotic positioning arm 208, which is also relative to the patient and the binding membrane 214.

[0143]

[0149] The system may further include a fluid system 220 that may be equipped with a fluid source, a cooling and degassing system, and a programmable control system. The fluid system is configured for external loading of the bonding membrane by automatic control of the fluid sequence. Details of the fluid system 220 will be described later.

[0144]

[0150] Figure 3A is a detail view of a coupling assembly or UMC 312 configured to couple a treatment and imaging system to a patient P. Figure 3A shows that the coupling assembly 312 may include a mechanical support arm 318, a robotic arm 308, a coupling membrane 314, an ultrasound treatment transducer 302, a fluid 322 placed within the membrane, an ultrasound imaging transducer 304, a flexible boot 324, a frame clamp 326, a fluid inlet / outlet 328, a boot clamp 330, a boot ring 332, a probe rotation handle 334, a vent / fluid tube 336, a probe cable 338, a membrane constraint mechanism 316, a bubble swipe 340, an upper UMC frame 342 and a lower UMC frame 344, a transducer assembly 346, and an ultrasound coupling medium 348 such as a gel or oil. Figure 3A shows how freely the robot arm and transducer assembly can move relative to the coupling assembly and membrane.

[0145]

[0151] The robotic arm and transducer assembly can move relative to the membrane and mechanical support due to the flexible boot 324, thereby allowing movement of the transducer assembly (e.g., treatment head) while the coupling assembly and membrane retain fluid. In this embodiment, the flexible boot acts as a splash guard to confine the fluid within the UMC during treatment or transducer movement, preventing the fluid from escaping, splashing, or splattering from the UMC. In this embodiment, the flexible boot is connected to the upper frame 342 and the transducer assembly 302. However, it should be understood that in other embodiments, the flexible boot can be connected to other components of the system or to protect other components of the system from splashing or fluid contact (e.g., it can be connected to the top of the treatment head or the distal end of the robotic arm, or it can extend upward to protect the robotic arm (and the surrounding workspace and devices)). In other embodiments, as will be described later, the UMC does not include a flexible boot; instead, the UMC is completely open on top to accommodate the transducer / robot arm and to allow unobstructed operation of the transducer / robot arm within a defined workspace.

[0146]

[0152] The coupling assembly 312 may include one or more sensors 349 positioned on, within, or inside the assembly. The sensors can be configured to measure or sense various parameters of the UMC or the coupling medium during treatment. For example, the sensors may include a pressure sensor configured to measure the pressure (of the fluid) in the UMC, a coupling medium or fluid level sensor configured to measure the fluid level in the UMC, a temperature sensor configured to measure the temperature (of the fluid) in the UMC, a flow sensor configured to measure the flow rate of the fluid flowing into and / or out of the UMC, a dissolved gas concentration, bubble or particulate sensor, a cavitation detection sensor, or an air detection sensor configured to detect air or bubbles in the coupling medium, or any other sensor that can be used to measure parameters of the UMC or the coupling medium that are useful before, during, or after treatment. Depending on the embodiment, the sensors may be positioned on or inside other components of the overall treatment system, or may be electrically coupled to or communicate with other components of the system. For example, sensors such as flow sensors, fluid level sensors, or pressure sensors can be placed in the fluid system or configured to communicate with the fluid system to assist in automatically filling or discharging the binding medium or fluid of the UMC. In another embodiment, a sensor placed within the UMC can communicate with a sensor placed on or inside the robot positioning arm. For example, proximity sensors, NFC chips or sensors, optical sensors, etc., can be used to communicate with the robot positioning arm to ensure that the robot positioning arm does not move beyond the boundaries of the UMC. In some embodiments, these sensors can be used to geolocate or geofence boundaries or areas within the UMC that the robot positioning arm (and therefore the treatment transducer) can move.

[0147]

[0153] To acoustically couple the UMC to the patient, the ultrasonic coupling medium 348 may include a layer of ultrasonically permeable gel or an oil may be applied to the patient's skin. While it is desirable to create a bubble-free and void-free contact area between the membrane and the patient, in practice, the application of the coupling medium may result in bubbles or other voids between the UMC and the patient. The medium can be applied by hand by the user or by a more controlled method such as spray application. Suitable materials for the gel or oil may include water, oils, creams, and gels. The layer of the ultrasonic coupling medium should be thin and of consistent thickness, biocompatible, immobile at the application site, and bubble-free in a material with minimal ultrasonic absorption. Examples of suitable medium materials include combinations of propylene glycol, glycerin, phenoxyethanol, Carbopol R940 polymer, water, and oils such as refined mineral oil or castor oil.

[0148]

[0154] The bubble swipe mechanism 340 can be configured to form a void- and bubble-free interface between the bonding assembly 312 and the patient's skin P. Depending on the embodiment, the bubble swipe may include systems and methods for facilitating the formation of a more uniform, bubble-free contact layer between the membrane and the patient after the membrane has been initially placed on the patient's body surface across a layer of ultrasonic gel or oil. The operation using the bubble swipe removes excess oil or gel, resulting in controlled, consistent wetting and fit between the membrane's contact surface and the patient. The bubble swipe process forms a more continuous, consistently thin layer of ultrasound-compatible gel or oil, reducing the risk of ultrasonic distortion and minimizing the presence of bubbles in the thin layer that could reduce ultrasound transmission. The membrane can also be further formulated to be transparent or translucent, allowing any residual bubbles to be directly visible.

[0149]

[0155] Figures 3B to 3D show an example of a bubble swipe mechanism in use. Referring to Figure 3A, the bubble swipe mechanism 340 can be positioned on the first side of the interface between the binding membrane 314 and the patient P. As described above, the UMC may include a fluid 322 placed within the membrane and a binding medium 348 placed between the membrane and the patient. The bubble swipe mechanism may include a rigid or flexible tube, cable, catheter, lumen or cable, which may include a certain range of materials (thermoplastic, metal, thermoplastic elastomer, rubber, etc.) and a certain range of cross-section, size and length. Depending on the embodiment, the bubble swipe may have a solid cross-section or may be hollow (as shown in Figures 3B to 3D). The cross-sectional shape is designed and configured to form a continuous air connection along the length of the bubble swipe and at the rear of the bubble swipe, so that air can be expelled when the two surfaces "tightly" or wet each other and air is not trapped between the membrane and the skin.

[0150]

[0156] Referring to Figure 3B, it can be seen that when the UMC membrane 314 is initially positioned in contact with the patient P and bonded to the patient by the bonding medium 348, there may be one or more bubbles 350 trapped in the medium that could cause suboptimal acoustic coupling between the UMC and the patient. In this example, the bubble swipe mechanism 340 can be positioned on the first side of the interface between the UMC and the patient (e.g., the left side in Figure 3B). Referring to Figure 3C, the bubble swipe mechanism 340 can be advanced through the interface between the UMC and the patient. As the bubble swipe mechanism moves between the UMC and the patient and passes through the medium 348, the bubble swipe mechanism can create a thinned thickness 352 of the medium by removing the bubbles 350 from the medium 348 by expelling them through the gap 354 created by the passage of the bubble swipe mechanism. Referring to Figure 3D, after the bubble swipe mechanism has completely passed through the interface between the UMC and the patient, the entire medium may have a thinned thickness of 352. In some embodiments, the bubble swipe mechanism can remove excess medium 356 from the interface.

[0151]

[0157] In one embodiment, the bubble swipe comprises a single hollow circular cross-section PVC tube having a continuous outer diameter of 2 mm to 8 mm. The length may exceed the width of the membrane. The bubble swipe may have intersecting holes or use porous material to actively remove air from the membrane / skin interface by applying a vacuum through the center of the hollow tube. These same intersecting holes or porous materials can also be used for ultrasonically compatible gel or oil application. The bubble swipe component may be supplied separately from the rest of the membrane / UMC or may be incorporated into the membrane, UMC or other subassemblies. The bubble swipe may be disposable or reusable. The bubble swipe may be a straight section stiff enough to withstand bending during application, or it may be stiff and pre-formed (e.g., curved). The bubble swipe may also be flexible and can be drawn between the membrane and the patient by linear motion or by a rotational sweep with fixed endpoints. Depending on the embodiment, the bubble swipe may have a mechanism for scraping and collecting excess gel or oil during the process to minimize manual removal of excess oil or gel. The bubble swipe may or may not rotate around its long axis during the swiping process.

[0152]

[0158] Figures 3E to 3F show embodiments for fixing the membrane within the UMC. As shown in Figures 2 and 3A, various mechanical fastening methods are available to enable fixing / sealing the membrane 314 within the frame housing. In these embodiments, the membrane 314 and the flexible boot 324 may be fixed by positioning the membrane 314 and the flexible boot 324 between the upper frame 342 and the lower frame 344, and by using a rotary device mechanism 358 to compress the upper and lower frames to form a seal and hold the membrane and boot in place. In the embodiments shown, both the membrane and the boot can be interlocked or molded to fit into corresponding keyholes / shapes in the upper and lower frames. Furthermore, the boot and membrane may be interlocked or molded with each other. In the embodiments shown, the compression is obtained from a two-piece assembly frame (upper and lower).

[0153]

[0159] Referring to Figure 3E, the T-shaped rotating device mechanism 358 can compress the bayonet catch barrel 360 in the upper frame 342 against the lower frame 344 by a bayonet catch pin 362 captured by the lower frame. In the embodiment of Figure 3F, the D-shaped rotating device mechanism 358 can compress against the upper frame 342 so as to fix the flexible boot 324 and membrane 314 to the lower frame 344. In this embodiment, it can be seen that the flexible boot and membrane are compressed into contact with each other and positioned between the upper and lower frames. In some embodiments, the flexible boot and membrane may interlock with each other or include other mechanisms to ensure that a fluid seal or watertight seal is reliably formed at the contact point between the upper and lower frames and the flexible boot and membrane. In other embodiments, the design uses a lower assembly frame (a frame that interfaces with the membrane and the mechanical arm) and an upper boot frame (a frame that includes an upper barrier through which the robot / therapeutic transducer passes), the membrane is positioned between the two frames, and a rotary compression screw is tightened to seal the membrane between the boot and the assembly.

[0154]

[0160] Figure 4A is another diagram showing an embodiment of a coupling assembly or UMC 412 including a flexible boot 424, a frame clamp 457, a fluid inlet / outlet 428, a boot clamp 458, a boot ring 460, a probe rotation handle 462, and a mechanical lock 464. In this embodiment, the coupling membrane can be held in place between the upper frame 442 and the lower frame 444 by the frame clamp 457. The flexible boot can be held in place between the boot ring 460 and the upper frame 442 by the boot clamp 458. The probe rotation handle 462 is configured to rotate the system's imaging probe relative to the therapeutic transducer. The mechanical lock 464 is configured to lock the transducer assembly (such as the therapeutic transducer) to the UMC. As described above, the fluid inlet / outlet 428 can couple the inside of the UMC (e.g., the volume between the membrane and the flexible boot) to a fluid system configured to deliver and maintain the volume of an acoustic coupling medium or fluid within the UMC.

[0155]

[0161] Figure 4B is an exploded view of another embodiment of the coupling assembly or UMC 412. The UMC may include a flexible boot 424, an upper frame 442, a lower frame 444, and a coupling membrane 414. It can be seen that the flexible boot is attached to the upper frame 442 by a boot clamp 458. Similarly, it can be seen that the membrane 414 is attached to the lower frame 444 by a frame clamp 457. As described above, the flexible boot can allow the transducer assembly / robot arm to move and rotate relative to the frame of the UMC and provide splash protection from fluids during treatment. However, it should be understood that in other embodiments, the flexible boot is not used or is unnecessary, and instead the top of the UMC is open to the atmosphere and the transducer assembly / robot arm.

[0156]

[0162] As shown in Figures 4C-4D, the mechanical lock 464 is configured to hold the transducer assembly in a predetermined position relative to the UMC while the UMC is filled with fluid before treatment. The coupling assembly and / or transducer assembly can be mechanically coupled to the mechanical lock by tabs, screws, clips, etc. After the UMC is filled with fluid, referring to Figure 4D, the mechanical lock can be released from the UMC to allow relative movement of the transducer assembly within the UMC.

[0157] Membrane / barrier film and related architectures

[0163] The membranes and barrier films can consist of a variety of biocompatible materials that enable conformal bonding to the patient's biostructure with minimal or no trapped bubbles that could interfere with ultrasound imaging and tissue disruption therapy, and that provide a sealing barrier layer between the patient's biostructure and the ultrasound medium housed within the workspace provided by the frame and assembly.

[0158]

[0164] The materials for the membrane and barrier film may include a variety of thermoplastic and thermosetting materials, as well as flexible elastomer biocompatible materials / polymers, such as permanent or bioabsorbable polymers. Furthermore, the UMC frame may also contain the same materials. Depending on the example, the membrane may be a pre-formed or flat rigid or semi-rigid polymer. Non-limiting examples of materials capable of forming membranes and barrier films include, but are not limited to, polyurethanes, polystyrene copolymers, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyrate), poly(phosphatine), polyesters, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl methyl acrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, polybutylene, aliphatic polyesters, glycerol, poly(amino acids), copoli(ether esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyalkylene oxalates, polyoxaesters, polyorthoesters, polyphosphazenes, and copolymers, block polymers, homopolymers, mixtures, and combinations thereof. In some embodiments, the film comprises a polystyrene copolymer and a block copolymer comprising ethylene, butadiene, butylene, and / or other styrene blocks, examples of which include styrene-butadiene-styrene (SBS) and styrene-ethylene-butylene-styrene (SEBS). In other embodiments, the film and barrier film may comprise formulations of various silicone compositions, including various silicones and silicone copolymers, and / or formulations of low molecular weight silicones or silicone-based oils. The film and barrier film may further comprise various additives, including oils or low molecular weight fluids, to improve thermal or optical stability, mechanical properties, biological properties (e.g., anti-infectiveness), and bactericidal stability, including vapor, thermal, chemical, radiation, and / or electron beam stability, and to plasticize or flexibly make the material and / or improve adhesion to other surfaces (backing materials, skin, etc.).In some embodiments, the membrane / barrier film contains 10 to 80 percent oil, and in other embodiments, 40 to 60 percent by weight. In some cases, the oil is paraffin oil. In some embodiments, additives also include blooming agents and / or other agents to improve surface properties. Some membrane / barrier film compositions may also include adhesives or one or more components of adhesive formulations to enable adhesion of the membrane / film to patient biostructures (e.g., skin), and constraint mechanisms intended to prevent the membrane from "escaping" from the body and / or frame / manifold.

[0159]

[0165] The membrane / barrier film may have a thickness ranging from 0.01 mm to 7 mm, and in some embodiments, preferably between 1 mm and 5 mm. In some embodiments, the membrane may have a thickness between 2 mm and 4 mm, and in other embodiments, the membrane may have a thickness between 2.5 mm and 3.5 mm. The membrane may have a tensile strength of >0.2 MPa. In some embodiments, the tensile strength may be between 0.4 MPa and 1 MPa. The membrane can be configured to stretch or elongate by up to 200%, and in some embodiments, up to 500% or up to 3000%. The thickness may be selected to balance physiological-mechanical properties, their impact on the acoustic cavitation / tissue disruption threshold, their suitability to patient biostructures, and the degree of membrane stretching and displacement (based on the set position and predicted ultrasonic medium mass and relative spatial distribution). The membrane may be transparent or translucent, and / or colored or lightly colored, including full or partial coloring or light coloring, and coloring or light coloring as marks or continuous / discrete regions. In some embodiments, the membrane is preferably transparent / translucent to allow visibility of the working space, any bubbles that may be present in the ultrasonic medium and sealed system, and to visualize the ultrasonic imaging probe contained within the central opening of the therapeutic transducer. This may include, for example, viewing the probe and its position / orientation (e.g., whether it is translated onto the skin and / or retracted from the skin).

[0160]

[0166] The membrane / barrier film may further include structural components such as frames or fixtures that can further improve the handling and usability of the acoustic / patient coupling system, including but not limited to setting up and removing procedures, and without including acoustic window sizes. The frames may consist of biocompatible metals and / or polymers, including but not limited to aluminum, aluminum alloys, acrylonitrile butadiene styrene (ABS), polyethylene, propylene, polyamide, and / or other impact-resistant materials. The frames of this disclosure may be positioned along the edge contour of the membrane / barrier film and may be continuous or divided into sections / lengths. Typically, the frame is positioned along the outer edge contour of the membrane. The frame may be positioned within the membrane / barrier film (e.g., on top of the molded film), or differently, may be contained on the membrane / barrier film, in which case the frame is molded around the membrane. Thus, the concepts of the disclosure may provide one or more means of interface with a membrane / barrier film, wherein the interface includes “rigid,” “semi-rigid,” and / or “flexible” interfaces, or combinations thereof. For example, a seal may be formed along the exposed / revealed flexible membrane / barrier film surface and edges, or along a rigid membrane frame, interface to a larger system “frame and assembly” described later. The interface may also include various mechanisms for reinforcing mechanical joining, fitting, interlocking, linking, and / or sealing, including, but not limited to, mechanical protrusions, grooves, pins, locks, and connecting structures, which can be manufactured in various heights, depths, grading / pitch, tapering, angles, separations, shapes, spacings, frequency / amount, and / or cutout degrees. In some embodiments, the membrane / barrier film may include a window for direct physical / acoustic access, where the edge region of the window (e.g., cutout) is adherable to the patient, and the edge region serves as a “mechanical support interface and frame-like mechanism”.

[0161]

[0167] The membrane / barrier film frame can be formed in various shapes and dimensions / sizes to accommodate the various working spaces and working space volumes provided by the bonding system, from smaller (<5 cm) transducers to larger (>20 cm along the long axis) transducers, and can be formed for location / position and for the associated required movement space corresponding to desired settings where different acoustic windows and conformal anatomical contouring (along the abdomen, thorax / chest, head / neck, limbs, etc.) are desirable, as well as target anatomical sites (e.g., abdomen, nerves, etc.). The frame can be fabricated from various metals, alloys, polymers / plastics, ceramics and / or composite materials and combinations thereof using integral molding, molding, machining and / or any useful / known manufacturing method. In some embodiments, the frame is preferably aluminum. In other embodiments, the frame is injection-molded plastic as derived from the above enumeration.

[0162]

[0168] Overall, the physiological-mechanical, chemical, dimensional, and processing-derived properties / qualities of the membranes of this disclosure provide the ability to control, and in some cases minimize, the acoustic cavitation initiation (tissue disruption) threshold requirements compared to other membranes. In some embodiments, membranes and barrier films can raise the cavitation threshold (and required driving amplitude) by more than 50% (above the threshold obtained directly through the skin and bound using degassed water). In other embodiments, this is 10-50% in similar inspections. In other embodiments, membranes / barrier films raise the threshold requirements by around 10%, and in preferred embodiments, raise the threshold requirements by only 5-10% or less. In some embodiments, membranes and barrier films provide this functionality without attenuating clinically relevant ultrasound imaging properties. In other embodiments, assuming direct acoustic access through the skin, windows as detailed above cannot alter the threshold. This includes B-mode or other forms of ultrasound imaging or post-acquisition image processing, some of which can be used to further enable multimodal image reconstruction, segmentation, alignment, and image fusion (in the form of MRI, CT, cone beam CT, fluoroscopy, and extended fluoroscopy).

[0163]

[0169] The therapeutic ultrasound systems described herein typically operate at a threshold voltage that is reasonably low and effective at the maximum penetration depth (to produce effective acoustic cavitation and tissue disruption).

[0164]

[0170] The use of membranes described herein offers advantages such as improved ease of use, enhanced targeting of difficult-to-reach tissue sites in patients, and improved patient comfort. However, membranes have the disadvantage of placing an additional layer of material between the therapeutic transducer and the patient's skin. These additional layers, specifically membranes, have two potential effects: transmission loss and strain.

[0165]

[0171] Transmission loss refers to the percentage of ultrasonic energy that is bonded through the membrane, and varies depending on the thickness, sound velocity, acoustic impedance, and how well a bubble-free interface can be achieved in the membrane and the gel or oil layer used between the membrane and the tissue. The membrane addresses this transmission effect by having an acoustic impedance close to that of water / tissue while maintaining a thinness sufficient to minimize loss within the membrane itself. Contact is achieved through a combination of extremely high compliance of the membrane to conform to the body, the self-wetting properties of the oil-mixed material, and coating techniques (bubble swiping) that allow for control of the interface.

[0166]

[0172] Controlling the level of strain is possible by ensuring that the medium and the membrane have similar sound velocities and by keeping the membrane as thin as possible. The level of strain is likely governed by the difference in sound velocities between the binding medium (e.g., water) and the tissue.

[0167]

[0173] The membrane properties that affect transmission loss and strain levels are related to the properties of the raw materials (composition and additives), the membrane design (e.g., film thickness, cross-section and surface roughness), the manufacturing process, and how the membrane is positioned on the patient to ensure a sufficiently large and effective contact area.

[0168]

[0174] The raw materials for the membrane can be selected to have an acoustic impedance as close as possible to the acoustic impedance of the ultrasonic medium, and must be biocompatible and compatible with both the ultrasonic medium and the gels and oils used on the patient's skin. The membrane material can also provide sufficient temperature resistance (e.g., the use of antioxidants that allow the material to withstand high temperatures in the final manufacturing process) and environmental resistance during storage. The material must not contain or have any additives that could reduce ultrasonic transmission (e.g., fine particles that could scatter ultrasound). Other material properties that may provide advantages in application include high transparency (allowing visualization of bubbles through the membrane), good puncture resistance (safety), avoidance of absorption by the ultrasonic medium (e.g., water), and low bubble trapping. Materials such as SEBS that can allow mineral oil to leach / bloom onto the surface can improve the quality of contact between the membrane and any oils or gels used on the patient's skin (i.e., this should reduce the risk of bubble trapping). However, the level of material that leach / blooms must be at a level that can be handled safely and does not contaminate the ultrasonic medium.

[0169]

[0175] The mechanical properties and design of the membrane must be specified to create a sufficiently large effective ultrasonic coupling area between the ultrasound treatment transducer and the patient's skin. The contact area must not contain trapped air or bubbles (which would result in transmission loss), and no load should be applied to the patient that could cause discomfort or injury or excessively alter the position of internal organs. To avoid variations in transmission loss, the cross-section of the membrane at the patient contact area must be consistent. The structural stiffness of the material must be sufficiently low so that the material is always under tension while in contact with the patient's skin, preventing skin folds, overlaps, or wrinkles that could trap air. A preferred embodiment is a flat membrane that stretches convexly when filled, resulting in an initial single contact point with the patient. As this membrane is pulled down or further expanded / filled, the skin contact increases radially, largely preventing the formation of trapped air pockets. Alternatively, a pre-formed convex membrane may be used, but the risk is that this embodiment may not have sufficient material tension at the initial contact point or during the placement phase.

[0170]

[0176] The manufacturing process also affects the presence of air bubbles in the material, particulate matter and contamination, variations in material composition, variations in film thickness, and surface roughness and defects. All of the above can potentially increase transmission loss.

[0171] Frame and assembly

[0177] The bonding solution frame and assembly, also sometimes called the ultrasonic medium container (UMC), bonding solution, and / or bonding device, is generally configured to hold, seal and support a membrane / barrier film and to enable / provide an interface with 1) an upper boot (e.g., upper sealing / enclosing), 2) a fluid inlet / outlet (e.g., receiving / removing the ultrasonic medium), 3) a mechanical arm, and 4) other mechanisms including, but not limited to, membrane support / restraint mechanisms, handles, locking mechanisms (for membrane frames, boots, and frame / assembly components), ventilation and bubble management, and imaging probe control. In some embodiments, the frame may incorporate a pressure sensor configured to measure the pressure of the medium within the UMC, which can be used to detect leak or overpressure events. The UMC may further include a pressure relief valve.

[0172]

[0178] Examples of frames and assemblies are partially shown in Figures 2–4C. Depending on the embodiment, the frame or UMC may include multiple parts, including top / upper and bottom / lower frame components, to allow external and internal access to the entire frame / assembly. This embodiment and similar embodiments may allow the membrane to be more easily positioned / oriented within the frame / assembly before sealing the UMC / binding solution in the upper boot and before filling with the ultrasonic medium. A frame / assembly including a lower frame component may include various pedestals, settings and / or connecting mechanisms (e.g., pins) for aligning / connecting the lower frame, membrane assembly, upper frame and / or upper boot.

[0173]

[0179] In some cases, a two-piece frame / assembly may include multiple frame fixing and compression mechanisms (e.g., knobs, clamps, cams, dials, screws, pins, etc.), the frame fixing mechanisms being configured to allow for rapid locking / unlocking (and compression of the membrane), efficient setting and sealing of the frame / assembly, and rapid interface with one or more mechanical support arms, one of which may include a robotic arm. Hereinafter, it is assumed that many fixing and compression mechanisms / methods may be employed as part of the present invention, and may interact / interface with frames / assemblies, boots, membranes and / or membrane fixing structures / mechanisms, etc.

[0174]

[0180] The frame and entire assembly may be designed and configured as having various profiles, including thin structures that minimize the thickness of the upper or lower frame, with the aim of reducing weight, spatial constraints, and potential collisions with other systems (e.g., conical beam CTs).

[0175]

[0181] Frame / assembly designs that offer various filling methods are also intended, and the filling orientation of the frame / assembly (and their respective / associated interface support arms, etc.) may also differ. Orientations may include, but are not limited to, horizontal, vertical, and / or angled / inclined methods, and static or dynamic orientations (e.g., fixing the robot arm or allowing controlled movement / angular displacement simultaneously with filling / discharging). Fluid inlets and outlets may be located in various places / positions. Depending on the embodiment, the fluid inlets and outlets may be configured to be located distal to the patient's body surface / operating table / bed in order to maximize the distance from the fluid communication interface.

[0176]

[0182] Figures 5A–5C show another embodiment of the UMC 512 configured to acoustically couple a therapeutic transducer 502 to a patient. Referring to Figures 5A–5B, the UMC may include a frame 543 configured to hold or support the coupling membrane 514. The frame may be flexible and adaptable (e.g., urethane composition) so that it can be positioned / fitted over and around the patient while also providing mechanical stability. In this embodiment, the UMC has an open architecture that provides an open workspace for the robotic arm 508 and the therapeutic transducer 502 to move without obstruction in the workspace (without constraints on the required movement / pattern or approach (angle, trajectory, etc.)). As shown in the figure, the frame itself may include a first opening 566 located on the patient contact side of the frame and a second opening 568 located on the opposite side of the first opening and configured to receive the therapeutic transducer and / or the robotic positioning arm. The frame may further include an adhesive 570 or other fastening mechanism positioned at or around the first opening for bonding the frame to the patient during treatment.

[0177]

[0183] Referring to Figure 5B, the membrane 514 is configured to hang over the edge of the frame and may include an adapted bag or other similarly shaped material. In another embodiment, the membrane may include only a single sheet attached to the bottom of the frame and covering only the opening 566. Thus, the membrane is configured to cover the first opening 566 and extend over it, while the second opening 568 can be left open to the atmosphere. As shown in Figure 5A, the frame may further include a lid 572 that can confine or hold the membrane in place. The lid may be hinged to the frame, for example, or may be completely removable. The lid itself also includes an opening 574, thereby allowing the transducer 502 and / or robot positioning arm 508 to pass through the openings 574 and 568 into the acoustic coupling medium placed within the frame and membrane. The embodiments shown in Figures 5A and 5B enable the use of robot controls (physical controls, such as a space mouse or joystick) to position the robot and / or to allow the user to grasp, position, and move the robot within the workspace, thus enabling "free driving."

[0178]

[0184] The membranes in Figures 5A and 5B may have windows to allow a direct acoustic interface with the skin, and each edge of the film / drape may contain adhesive to allow the formation of a watertight seal around the edges of the windows and to support the acoustic medium (degassed water) placed within the formed workspace. This may be held / mechanically fixed and supported by a frame using latches, clips, etc., and in some embodiments, the film / drape may be sealed over / around the distal end of the robot (and therapeutic transducer) to prevent splashing / spilling. In some cases, as in this embodiment, the latches / clips may be integrated with a hinged frame that confines the film / drape within the frame. The assembly / container may be configured to support the film / drape and minimize escape or movement from the patient.

[0179]

[0185] In another embodiment, referring to Figure 5C, the frame 543 may include a bellows assembly. Similar to the embodiments shown in Figures 5A and 5B, the bellows frame may include first and second openings 566 and 568 and may be configured to be used with a binding membrane (not shown), which is a bag or drape-type membrane (as shown in Figure 5B) that either seals / blocks only the first opening or covers the first opening but allows the second opening to be opened to accept a binding medium and / or a transducer and / or robotic arm.

[0180]

[0186] Depending on the embodiment, the frame may include an arm interface that allows the frame (and the entire subsystem) to interface with other structures, including operating table rails, carts, or other mechanical structures, via a mechanical support arm. The mechanical support arm may have various degrees of freedom to allow for various setting configurations / orientations of x, y, and z, as well as pitch, roll, and yaw.

[0181]

[0187] An example workflow for this method may include adjusting the binding medium to 15°C to 25°C and less than 40% dissolved oxygen, or between 5% and 60% dissolved oxygen (for example, the binding medium may be tap water adjusted to the above conditions by a degassing pump and cooling device), recording the temperature and oxygen concentration in study-specific case reports, performing system checks, calibrating the system's crosshairs (sights), preparing the patient's skin to remove foreign matter, identifying the treatment site by ultrasound, marking the patient's skin with ink based on the location of the treatment site, applying benzoin ink (adhesion promoter) and the binding medium container drape to the skin, assembling the UMC, mounting the UMC and placing it on the binding medium container drape, filling the UMC with approximately 16 liters of binding medium, and performing ultrasound treatment. The treatment head of the treatment system can be immersed in the binding medium and inspected for trapped air. Using ultrasound image guidance, free-movement control, and a space mouse, the treatment head can be positioned relative to the target during treatment.

[0182] ultrasonic medium

[0188] As described above, the ultrasonic medium may include any suitable medium that can provide sufficient and useful acoustic coupling to enable tissue disruption therapy and adequate clinical imaging (e.g., ultrasound). The ultrasonic medium as part of the system may include, but is not limited to, a variety of aqueous solutions / mediums that have preferred or more preferred acoustic qualities, including the ability to match the velocity of sound, including mixtures with other cosoluble fluids. Examples of media may include degassed water and / or mixtures / cosolutions of degassed water with various alcohols such as ethanol.

[0183] Mechanical support arm and arm architecture

[0189] Various designs and configurations of mechanical support arms (and arm architectures) can be employed to support acoustic / patient coupling systems, including providing users with an efficient and ergonomic workflow. The support arms may be configured with a set of degrees of freedom, including but not limited to x, y, z, pitch, roll, and yaw, and additional interface mechanisms that may allow for additional height adjustment or translation.

[0184]

[0190] An arm can contain a variety of joints and compartments of different numbers and types. Typically, an arm can contain at least two compartments. Depending on the configuration, an arm can contain three to five compartments.

[0185]

[0191] The arm is also configured to interface proximal to the main support base or base interface (e.g., robot, operating table, operating table / bed rail, cart, floor fixture, etc.) and distally to the frame / assembly and the entire "UMC" or "binding solution". This particular distal interface may further include a mechanism for controlling the position / orientation of the frame / assembly at the frame / assembly interface.

[0186]

[0192] For example, in some embodiments, the arm / frame interface may include a ball joint list. In another embodiment, the interface may include the use of a gimbal list or an adjustable pitch-roll control list. These interfaces may further be employed with specific user interfaces and inputs to assist interaction with various lists, and they may include additional handles or knobs (as a non-limiting example) to allow for further positioning of the UMC / coupling solution. For example, a gimbal list may be useful in allowing the frame / assembly to have three degrees of freedom (independent of the arm's degrees of freedom), including pitch, roll, and yaw adjustments.

[0187]

[0193] A support arm, configured with an armlist further interfaced with a frame / assembly, may include mechanisms such as brakes and quick releases, including cable brakes or electronically actuated brakes, which can interact individually or collectively with one or more axes. The support arm may also include an electronic lift system and a base support. In some embodiments, these lift systems / base supports are located in the same location as the robot arm base, and the robot arm includes a tissue lithotripsy transducer configured to reside / operate within a sealed binding solution. In other embodiments, the support arm is located on a separate cart. In some cases, the separate cart may include a fluid system or a user console. In other embodiments, the cart interfaces with a bed / operating table, including but not limited to rails, sides, and / or a bed / operating table base. In other embodiments, the cart interfaces with a floor-mounted structure / base that can manage weight and tilt requirements.

[0188] Fluid systems, control systems, and system architectures

[0194] As part of the overall fluid management, the tissue disruption system, including the acoustic / patient binding system, may be configured to include an automated fluid system that primarily serves to provide a storage area for the preparation or use of the binding medium, and preparation may include the ability to degas, cool, monitor, prepare, load / fill, and remove / discharge the binding medium to and from the frame / assembly. The fluid system may include an emergency high-flow system for rapid discharge of the binding medium from the UMC. Depending on the embodiment, the fluid system can be configured for single-use or reuse of the binding medium. Depending on the embodiment, the fluid system may provide positive air pressure or vacuum to perform leak testing of the UMC and membrane before loading the binding medium. Vacuum assistance can also be used to remove air from the UMC during the loading process. The fluid system may further include filters configured to prevent particulate contaminants from reaching the UMC.

[0189]

[0195] Figures 6A and 6B show one embodiment of the fluid system. As shown in the figures, the fluid system allows a clinician to prepare an ultrasonic medium and transport it from a clinical water source (e.g., hospital tap water or other) to the treatment room, and as part of this, it may include a mobile fluid cart 676 that can be rapidly degassed (e.g., 4-6 liters / minute) to minimize water preparation time, treatment setup, and rotation time, and the cart can be brought in / out during treatment (e.g., not needed during treatment).

[0190]

[0196] The fluid system cart may further include one or more pumps 678 configured to allow pumping fresh water and wastewater to and from the coupling system (on the patient) using a dedicated injection (cleaning) tank 680 and discharge (wastewater) tank 682. To enable degassing, one or more pumps 678 may be configured to pump fresh water to a degassing module 684, which includes a filter, a degassing contactor and a vacuum pump. One or more pumps also fill and discharge the coupling solution to and from the UMC. One or more pumps may further allow pumping purging of the discharge / wastewater tank.

[0191]

[0197] The cart can be powered via standard electrical fixtures / connectors and via battery 686 to enable portable or grid-independent use. The battery can also supply emergency power. The cart may also include a nitrogen tank 688 and / or an air compressor 690 to enable blowdown of tubing / piping so that tubing / piping can be reliably kept dry / clean (under a nitrogen blanket). Depending on the embodiment, the cart may also include a variety of user interfaces for enabling tubing connections to the binding solution and water source (and wastewater container), and a physical and software control system or electronic controller 692 configured to program / monitor / report water conditions and parameters. Parameters may include oxygen saturation, temperature, particulate debris, pH, mixing ratio, flow rate, fill level, power level / battery level, etc., which can be detected in real time by any number of sensors placed inside and around the system. Parameters can be read on a UI screen on the fluid system cart and / or displayed / controlled (via a software UI) on a treatment system cart display.

[0192]

[0198] As described above, the fluid system may be implemented in the form of a mobile fluid system cart. The cart may include an injection tank, a discharge tank, a degassing module, a filling pump, a discharge pump, an inert gas tank, an air compressor, tubing / connectors / piping, an electronic manual control system, an input device, a power supply, and one or more batteries. The cart may optionally be a system for evaluating the performance of the tissue disruption system and related system diagnostics (configured to accommodate the required water volume and the working space for the therapeutic transducer).

[0193] This may also include check containers / storage units.

[0199] The injection tank can generally hold up to approximately 80 liters of the medium (e.g., water). In some cases, the volume may be as small as 40 liters.

[0194]

[0200] The exhaust module may include a filter or degassing membrane configured to remove particulate matter / debris, a degassing contactor, and a vacuum pump or peristaltic pump for moving fluid within the system. In some embodiments, the filter may have a pore size of 0.2 micrometers. The degassing contactor can be pulled down to parts per billion at a flow rate of approximately 3 gallons (11 liters) per minute and can remove dissolved O2, CO2, and N2 gases. The vacuum pump may include important features such as pure transfer and discharge, high compatibility with vapor and condensation, chemical resistance, and airtightness (ultra-low leakage). In some embodiments, the vacuum pump can be pulled down to 8 tors. In some embodiments, the degassing system may omit the pump and rely on the flow rate of a water source (e.g., tap water flow rate) to move fluid within the system.

[0195]

[0201] One or more pumps, including a filling pump, may be configured to pump water to a degassing module and a medium to a frame / assembly (e.g., UMC or binding solution), and also to pump any excess input to a receiving container (e.g., a sink, tub, storage container, drain pipe, etc.). In some embodiments, the filling pump is configured to pump 0.1 to 10 liters / minute using a 115V AC power supply.

[0196]

[0202] One or more pumps, including a drainage pump, can be configured to de-aqueous the frame / assembly (e.g., UMC or binding solution) and the system inspection container, pumping the waste medium / tank into a container (outside the system).

[0197]

[0203] The wastewater tank receives the ultrasonic medium (degassed water) after treatment, and provides a function that prevents contamination and eliminates the need to reuse individual treatment supplies.

[0198]

[0204] The inert gas tank contains a built-in compressed inert gas (such as nitrogen) intended for storage to provide a gas blanket to the system when not in use.

[0199]

[0205] The air compressor is configured as part of the system to assist with bulk fluid removal and post-treatment drying / drainage.

[0200]

[0206] Plastic and / or metal tubing / connectors / piping are configured to allow fluid and air communication throughout the system and the acoustic / patient coupling system. These may also include various components such as valves (e.g., two-way valves, three-way valves, etc.).

[0201]

[0207] Electronic and manual controls provide user-facing system controls for all functions of the system, including but not limited to pump control and degassing control. The control system may further include a variety of in-line and on-board sensors for sensing temperature, pressure, flow rate, dissolved oxygen concentration, volume, and other parameters.

[0202]

[0208] The fluid system and cart may also include various electrical connections for power, including the use of external power, and / or may include a battery / toroid to enable a cordless, fully mobile configuration. This allows the fluid cart to be moved for preparation / setup of tissue lithotripsy procedures and then carried away after all fluid-related workflow steps are completed, so that the fluid cart does not have to be left next to the patient during the procedure / treatment.

[0203]

[0209] The architecture and design of the fluid system cart may also include a handle, individual or centrally locking casters, an upper work surface, a built-in user display device, and connectivity (e.g., Ethernet), and may be designed to allow for the further incorporation of support arms depending on the embodiment. Furthermore, long / extension tubes may be provided to accommodate in-imaging system filling / draining, for example, if it is desirable for use in a CT or MRI to avoid having the total volume of medium / water near the scanner, and / or if setting-up filling is required to further evaluate pre- / post-image / body separation filling.

[0204]

[0210] Figures 7A to 7G illustrate one method for filling a UMC, such as the UMC described herein. Referring to Figure 7A, one filling method begins with the assembly of the UMC 712, the membrane 714, and the transducer assembly 702. In this embodiment, the transducer can be fixed or locked to the UMC with a mechanical lock 764 to prevent the transducer from moving relative to the UMC during filling. Figure 7A also shows that a front plate 794 can be attached to the UMC to prevent the membrane from expanding too far beyond the UMC during filling. This configuration provides a sealed unit. Next, referring to Figures 7B and 7C, the entire assembly can be rotated to a vertical or near-vertical position and filled with the coupling fluid (such as by the fluid system described above). The assembly can be filled through the injection / discharge ports of the coupling vessel. In some embodiments, these injection / discharge ports are located at the top / top of the coupling vessel when the coupling vessel is oriented vertically. In other embodiments, the injection / discharge ports are located at the bottom / bottom of the coupling vessel when the coupling vessel is oriented vertically. This vertical UMC filling has potential advantages, such as allowing manual or mechanical visualization of the filling process through a (transparent) membrane, which both allows for confirmation that bubble-free filling has been successfully achieved directly through the membrane and provides an opportunity for manual or automated manipulation and removal of bubbles in the ultrasonic medium. Another advantage is that the filling process can be carried out without the need to vent air from the center of the concave ultrasonic treatment transducer, which is required in the case of horizontal filling methods.

[0205]

[0211] Vertical filling can be performed with the ultrasonic transducer in a vertical or horizontal orientation. Vertical filling may require the use of a mechanical lock between the UMC frame and the transducer assembly (as described above). This mechanical lock can be a separate component or can be integrated into the UMC frame or transducer assembly.

[0206]

[0212] Positive air pressure may be used before filling the ultrasonic medium to expand the membrane and inspect for air leaks (due to membrane sealing defects or incorrect assembly). Alternatively, vacuum testing may be used to inspect for similar defect modes before filling.

[0207]

[0213] One objective of the filling process is to reduce the risk of air bubbles forming, which would otherwise need to be vented from the system. To enable filling under conditions where the risk of air bubble formation is low, the filling port can be located at the lowest point of the UMC frame. Alternatively, if the fluid is filled through a tube or structure connecting the port to the lowest point in the volume, the filling port may be located elsewhere. To prevent air bubbles from entering the UMC, a filter or air bubble trap can be incorporated into the fluid filling port.

[0208]

[0214] The UMC system must be designed to have no sharp corners or edges that could trap air bubbles during filling. Alternatively, locations where bubbles could be trapped may be identified, thereby preventing air in those locations from directly entering the volume of the ultrasonic medium between the transducer and the patient, which is the only volume in which bubbles could affect ultrasonic performance.

[0209]

[0215] Air can be vented during filling through one or more ports at the highest point of the UMC. To increase the effective area from which air can escape, a manifold structure can be used as part of the venting system, which further allows for a wider range of orientation tolerances for the UMC assembly during filling. The filling process may use a fluid flow or vent from the center of the transducer through the ultrasonic probe to facilitate the removal of trapped air bubbles between the probe and the transducer. The vents can be opened to the environment or to atmospheric pressure in the fluid system cart during the filling process. In this case, there is a risk that the weight of the ultrasonic medium will deform the membrane during filling, causing the membrane to bulge out from the front of the UMC. This can prevent normal filling or result in a significant overflow of the membrane. To mitigate this, the UMC may be angled from a vertical position, or a transparent support plate may be used in front of the membrane. Alternatively, a vacuum system can be used to actively evacuate from the UMC and maintain the shape of the membrane (vertically, without a support plate). In this case, the fluid filling rate and air removal (vacuum level) can be balanced to maintain a stable membrane shape until all the air inside the UMC is exhausted.

[0210]

[0216] Next, referring to Figure 7D, after filling the UMC, excess fluid can be drawn out of the UMC (for example, by using a fluid system) to pull the membrane against the transducer, minimizing the mass of the UMC and transducer assembly, thereby making the system as lightweight as possible so that the system can be more easily placed on the patient. The fluid injection port and exhaust port (and fluid port) can be designed to prevent accidental blockage of the ports by the membrane. Referring to Figure 7E, the mechanical lock can be released. In Figure 7F, the membrane constraint mechanism 716 can be attached to the UMC. As described above, the membrane constraint mechanism can be configured to prevent the membrane from expanding or moving beyond the boundaries of the UMC so that the entire surgical treatment area is ensured to maintain acoustic coupling during treatment. In Figure 7G, the entire assembly can be rotated back to a horizontal position in preparation for treatment or procedure.

[0211]

[0217] An active vacuum pump system may be used to improve the rate of air removal at the exhaust site while allowing control of the air pressure within the UMC. This method can be used to make it easier to prevent the membrane from expanding beyond the front of the UMC.

[0212] System Transformation Mode

[0218] As described and disclosed above, various substitutions of the system deformation modes of the acoustic / patient coupling system are envisioned and are not limited to the concepts described herein.

[0213]

[0219] The core systems and subsystems may be configured separately from or integrated into the various overall architectures of the tissue disruption system. This may include various configurations of how the "UMC / patient connection" and the frame / assembly system are supported by the "arms."

[0214]

[0220] For example, the UMC and arm may be in a separate configuration (e.g., not part of a robot or fluid system), including a tableside / bedside configuration.

[0215]

[0221] In another embodiment, the UMC and arm may be integrated with a treatment cart (for example, one housing a robot and a tissue lithotripsy generator).

[0216]

[0222] In different embodiments, the UMC and arm may be integrated with the fluid system cart.

[0217]

[0223] In another embodiment, it may be integrated with an imaging operation unit / user console (for example, including a graphical user interface and physical control / control panel for user control of treatment, imaging, and robots).

[0218]

[0224] In all of the above cases, various configurations / combinations may be set up in simple treatment rooms, operating rooms, combined treatment rooms, imaging rooms (e.g., CT, MRI, etc.), catheterization rooms (e.g., cone beam CT, extended fluorescence fluoroscopy), or otherwise in clinical room environments, etc.

[0219]

[0225] In some embodiments, all control of all systems may be interfaced through a single physical display or display center / user console (including the fluid system), and in other embodiments, each individual "subsystem, e.g., fluid system cart" may include its own control / display for satellite and independent control.

[0220]

[0226] In another embodiment, the binding system may include a cavitation detection or passive cavitation detection device for detecting the initiation, maintenance, and completion of tissue disruption.

[0221] Methods, applications, and workflows

[0227] The systems disclosed above can utilize various workflows for setup, use, and removal. In most cases, UMC / frame / assembly filling is performed after a series of initial workflow steps to configure the membrane / barrier film to fit the patient and / or frame / assembly.

[0222]

[0228] The filling steps and methods may allow for horizontal filling, where the working space of the UMC / frame / assembly is filled in a relative appropriate location / method for the procedure. In other workflows, the working space may be filled vertically to minimize / reduce air bubble trapping under the treatment transducer. Both horizontal and / or vertical methods (or other methods) may include an exhaust step to remove residual air bubbles if air bubbles are detected in any part of the procedure, either before treatment planning or treatment, or conversely, if it is permitted / possible to control those air bubbles.

[0223]

[0229] Another part of the workflow involving these steps may include the steps and timing of docking the robotic arm to the treatment head, and / or the steps and timing of positioning the treatment head within the UMC / frame / assembly. In some configurations and workflows, the robotic arm may interface with the treatment head before inserting the treatment head into the UMC / frame / assembly workspace. In other configurations and workflows, the UMC / frame / assembly may be assembled, filled, de-bubbled, etc., before being docked to the robotic arm quick-connect interface. In some cases, these setup steps may be performed directly in / on the patient as part of the procedure setup.

[0224]

[0230] Throughout these steps and flows, the user may be able to image the patient and patient biostructure locally using an ultrasound system integrated with a tissue disruption system. In some cases, the user may modify / change the UMC / frame / assembly setting position, angle, etc., based on this imaging to obtain the best acoustic window and approach to a user-defined target. This may also vary depending on the application (e.g., settings for treating abdominal tumors with known kinetic sources, acoustic blockage and other issues, and settings for relatively stable, consistent known blockage in the head / brain). Various considerations and novel setting and workflow techniques are described in the supporting documentation, examples, and drawings provided. <Note> [Note 1] It is an ultrasound therapy system, A binding container configured to come into contact with the patient's skin, the binding container being at least partially filled with an acoustic binding medium, An ultrasonic treatment transducer at least partially immersed in the acoustic coupling medium, A system comprising a robotic positioning arm coupled to the ultrasonic therapy transducer, configured to move the ultrasonic therapy transducer relative to the patient within the coupling container while maintaining acoustic coupling with the patient via the acoustic coupling medium. [Note 2] A system as described in Appendix 1, wherein the coupling container includes an open architecture that provides an open workspace for the robot positioning arm to move independently of the coupling container. [Note 3] The system as described in Appendix 1, further comprising a membrane configured to contact the patient's skin in the binding container. [Note 4] The system as described in Appendix 3, further comprising a bubble removal mechanism configured to remove bubbles and / or air between the membrane and the patient's skin. [Note 5] The system as described in Appendix 3, further comprising a flexible boot assembly attached to the coupling container, wherein the flexible boot assembly is configured to allow movement of the ultrasonic therapeutic transducer with the acoustic coupling medium contained within the coupling container. [Note 6] The system as described in Appendix 5, wherein the flexible boot assembly is further attached to the ultrasonic treatment transducer. [Note 7] The system described in Appendix 1, further comprising a fluid system including an acoustic coupling medium source, a cooling and degassing system, and a programmable control system configured to automatically control the fluid level of the acoustic coupling medium in the coupling container. [Note 8] A system as described in Appendix 7, wherein the fluid system is separate from the robot positioning arm. [Note 9] The system described in Appendix 1, further comprising a support arm configured to support the coupling container. [Note 10] The system described in Appendix 9, wherein the support arm is configured to be moved independently of the robot positioning arm. [Note 11] A system as described in Appendix 9, wherein the support arm is connected to the fluid system. [Note 12] A system as described in Appendix 9, wherein the support arm is connected to the treatment cart of the tissue disruption system. [Note 13] The system described in Appendix 9, wherein the support arm is connected to the patient bed. [Note 14] The system described in Appendix 10, wherein the support arm is movable between 4 degrees of freedom and 8 degrees of freedom. [Note 15] A system as described in Appendix 7, wherein the fluid system is configured to communicate with a sensor located on or inside the UMC. [Note 16] A system as described in Appendix 7, wherein the fluid system further includes one or more sensors configured to detect parameters of the fluid system or the acoustic coupling medium. [Note 17] A system as described in Appendix 15, wherein the sensor is selected from the group consisting of a pressure sensor, a coupled medium level sensor, an optical sensor, a dissolved gas concentration sensor, a bubble or particulate sensor, a temperature sensor, a flow sensor, a cavitation detection sensor, and a proximity sensor. [Note 18] A system as described in Appendix 5, wherein the coupling container includes a frame. [Note 19] A system as described in Appendix 18, wherein the frame includes a biocompatible material. [Note 20] The system described in Appendix 19, wherein the frame is made of aluminum and aluminum alloy, stainless steel, polyethylene, high-density polyethylene, polypropylene, polyacrylonitrile butylene styrene, polycarbonate, polyamide-imide, polyurethane, polystyrene copolymer, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyrate), poly(phosphatine), polyester, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl methyl acrylate, and polyvinylpyrrolidone. A system comprising a biocompatible material selected from the group consisting of polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, polybutylene, aliphatic polyester, glycerol, poly(amino acid), copoli(ether-ester), polyalkylene oxalate, polyamide, poly(iminocarbonate), polyalkylene oxalate, polyoxaester, polyorthoester, polyphosphazene, and copolymers, block polymers, homopolymers, mixtures, and combinations thereof. [Note 21] A system as described in Appendix 18, wherein the frame includes an upper frame and a lower frame, and the upper frame is configured to be detachably attached to the lower frame. [Note 22] The system as described in Appendix 21, wherein the flexible boot assembly is removably attached to the upper frame. [Note 23] The system as described in Appendix 22, wherein the membrane is removably attached to the lower frame. [Note 24] A system as described in Appendix 21, wherein the flexible boot assembly and the membrane form a watertight seal between the upper frame and the lower frame. [Note 25] The system described in Appendix 21, wherein the membrane is held in a predetermined position between the upper frame and the lower frame. [Note 26] The system described in Appendix 18, wherein the frame includes a first opening on the side of the frame configured to contact the patient's skin. [Note 27] The system described in Appendix 26, wherein the membrane is attached to the frame and covers only the first opening. [Note 28] The system as described in Appendix 26, wherein the membrane includes a bag and is configured to be placed inside the binding container so as to cover the first opening. [Note 29] The system as described in Appendix 28, wherein the frame further includes a second opening opposite to the first opening. [Note 30] The system described in Appendix 29, wherein the bag is configured to rest on the edge of the frame that defines the second opening. [Note 31] The system described in Appendix 1, wherein the coupling container includes an additional flexible support structure including a bellows or a constraint mechanism. [Note 32] A system as described in Appendix 1, wherein the membrane comprises a biocompatible material configured to bond the bonding vessel and the acoustic bonding medium to the patient's skin with minimal or no trapped air bubbles. [Note 33] The system described in Appendix 32, wherein the film comprises silicone polyurethane, polystyrene copolymer, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyrate), poly(phosphatine), polyester, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl methyl acrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, polybutylene, and poly A system comprising thermoplastic elastomers selected from the group consisting of styrene, polybutadiene, polystyrene-ethylene-butadiene-styrene, aliphatic polyester, glycerol, poly(amino acid), copoli(ether-ester), polyalkylene oxalate, polyamide, poly(iminocarbonate), polyalkylene oxalate, polyoxaester, polyorthoester, polyphosphazene, and copolymers, block copolymers, homopolymers, mixtures, and combinations thereof. [Note 34] A system as described in Appendix 32, wherein the film has a thickness between 2 mm and 4 mm. [Note 35] A system as described in Appendix 32, wherein the film has a thickness between 2.5 mm and 3.5 mm. [Note 36] A system as described in Appendix 32, wherein the film contains 10% to 80% by weight of oil. [Note 37] A system as described in Appendix 32, wherein the film contains 40% to 60% by weight of oil. [Note 38] A system as described in Appendix 32, wherein the membrane has a tensile strength of >0.2 MPa. [Note 39] The system described in Appendix 32, wherein the membrane further includes a membrane frame positioned along the edge of the membrane. [Note 40] A system as described in Appendix 39, wherein the membrane frame is configured to interface with the bonding vessel. [Note 41] A system as described in Appendix 7, wherein the fluid system is configured to deliver the acoustic coupling medium to the coupling container at a flow rate of 1 liter / min to 10 liters / min. [Note 42] A system as described in Appendix 7, wherein the fluid system is configured to maintain the dissolved oxygen level in the acoustic coupling medium at less than 40%. [Note 43] A system as described in Appendix 7, wherein the fluid system is configured to maintain the temperature of the acoustic coupling medium between 10°C and 30°C. [Note 44] A method of acoustically coupling the treatment system to the patient's skin before treatment, A step of receiving an ultrasound therapy system which includes a binding container having a membrane and an ultrasound therapy transducer configured to move freely within the binding container, The steps include: mechanically locking the coupling container and the ultrasonic treatment transducer to prevent the coupling container from moving relative to the coupling container; The steps include: filling the bonding container and delivering a flow of bonding medium to the bonding container in such a manner as to remove air from the bonding container; A method comprising the step of placing the aforementioned membrane in contact with the patient's skin. [Note 45] A method according to Appendix 44, further comprising the step of rotating the binding container and the ultrasonic treatment transducer by about 90 degrees in order to position the binding container vertically, prior to the delivery step. [Note 46] A method according to Appendix 45, wherein the delivery step further includes the step of delivering the flow of the binding medium into the uppermost part of the binding container when the binding container is oriented vertically. [Note 47] A method according to Appendix 46, further comprising the step of visualizing the delivery of the flow of the binding medium to the container so that it can be seen through the film. [Note 48] A method according to Appendix 45, further comprising the step of automatically filling the bonding container with the bonding medium by a fluid system separate from the bonding container. [Note 49] A method according to Appendix 48, wherein the automatic filling step further includes a step of automatic filling based on sensor feedback from within the coupling container or the fluid system. [Note 50] A method according to Appendix 49, wherein the sensor feedback includes the fluid level in the container. [Note 51] A method according to Appendix 50, wherein the sensor feedback includes the detection of undesirable bubbles in the bonding container. [Note 52] A method according to Appendix 50, wherein the sensor feedback includes the detection of undesirable cavitation in the binding vessel. [Note 53] A method according to Appendix 45, further comprising the step of applying positive air pressure to the coupling vessel before the delivery step in order to inspect for air leaks in the membrane or the coupling vessel. [Note 54] A method according to Appendix 45, further comprising the step of exhausting air from the coupling container. [Note 55] A method according to Appendix 54, wherein air is exhausted from a port located at the highest point of the coupling container. [Note 56] A method according to Appendix 54, wherein air is exhausted from the central hole of the treatment transducer. [Note 57] A method according to Appendix 45, further comprising the step of rotating the coupling container and the ultrasonic treatment transducer back to a horizontal orientation before the arrangement step.

Claims

1. It is an ultrasound therapy system, Ultrasonic medium container (UMC), A binding membrane (214) attached to the ultrasonic medium container (UMC) and configured to come into contact with the patient's skin, wherein the binding membrane (214) is at least partially filled with an ultrasonic medium so that the ultrasonic medium container (UMC) and the binding membrane (214) can stretch the binding membrane (214) and conform to the patient's skin, A membrane constraint mechanism (216) extending from the patient to the ultrasonic medium container (UMC) and coupled to the ultrasonic medium container (UMC), wherein the membrane constraint mechanism (216) is configured to restrict the expansion of the coupling membrane when the ultrasonic medium container is at least partially filled with the ultrasonic medium, An ultrasonic treatment transducer is disposed within the ultrasonic medium container (UMC), at least partially immersed in the ultrasonic medium, and configured to be movable independently of the ultrasonic medium container without moving the ultrasonic medium container. A system comprising a robotic positioning arm coupled to the ultrasonic therapy transducer, the robotic positioning arm configured to move the ultrasonic therapy transducer relative to the ultrasonic medium container without moving the ultrasonic medium container, while maintaining acoustic coupling between the ultrasonic therapy transducer and the patient via the ultrasonic medium.

2. A system according to claim 1, wherein the ultrasonic medium container includes an open architecture that provides an open space with respect to the ultrasonic therapeutic transducer so that the robot positioning arm moves the ultrasonic therapeutic transducer independently of the ultrasonic medium container without moving the ultrasonic medium container.

3. A system according to claim 1, further comprising an elongated bubble removal mechanism (340) configured to pass through the interface (350) between the binding membrane and the patient's skin in order to remove bubbles and / or air in the acoustic coupling medium between the binding membrane and the patient's skin.

4. The system according to claim 1, further comprising a flexible boot attached between the ultrasonic medium container and the ultrasonic therapy transducer, which is deformable without deforming the bonding membrane, wherein the flexible boot is configured to allow movement of the ultrasonic therapy transducer while the ultrasonic medium is contained within the ultrasonic medium container.

5. A system according to claim 1, further comprising a fluid system system including an ultrasonic medium source, a cooling and degassing system, and a programmable control system configured to automatically control the fluid level of the ultrasonic medium in the ultrasonic medium container.

6. The system according to claim 5, wherein the fluid system is separated from the robot positioning arm.

7. The system according to claim 1, further comprising a support arm configured to support the ultrasonic medium container.

8. The system according to claim 7, A system in which the support arm supporting the ultrasonic medium container is configured to move independently of the robot positioning arm, which is coupled to the ultrasonic treatment transducer, without moving the robot positioning arm.

9. The system according to claim 7, wherein the support arm is connected to a fluid system including an ultrasonic medium source.

10. The system according to claim 7, wherein the support arm is connected to a cart.

11. The system according to claim 7, wherein the support arm is connected to a patient bed.

12. The system according to claim 8, wherein the support arm is movable between 4 degrees of freedom and 7 degrees of freedom.

13. The system according to claim 5, wherein the fluid system is configured to communicate with a sensor located on or inside the ultrasonic medium container.

14. A system according to claim 5, wherein the fluid system further comprises one or more sensors configured to detect parameters of the fluid system or the ultrasonic medium.

15. The system according to claim 13, wherein the sensor is selected from the group consisting of a pressure sensor, a bound medium level sensor, an optical sensor, a dissolved gas concentration sensor, a bubble or particulate sensor, a temperature sensor, a flow sensor, a cavitation detection sensor, and a proximity sensor.

16. The system according to claim 4, wherein the ultrasonic medium container includes a frame.

17. The system according to claim 16, wherein the frame comprises a biocompatible material.

18. The system according to claim 17, wherein the frame is made of aluminum and aluminum alloy, stainless steel, polyethylene, high-density polyethylene, polypropylene, polyacrylonitrile butylene styrene, polycarbonate, polyamide-imide, polyurethane, polystyrene copolymer, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyrate), poly(phosphatine), polyester, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl methyl acrylate, and polyvinylpyrrolidone. A system comprising a biocompatible material selected from the group consisting of polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, polybutylene, aliphatic polyester, glycerol, poly(amino acid), copoli(ether-ester), polyalkylene oxalate, polyamide, poly(iminocarbonate), polyalkylene oxalate, polyoxaester, polyorthoester, polyphosphazene, and copolymers, block polymers, homopolymers, mixtures, and combinations thereof.

19. The system according to claim 16, wherein the frame includes an upper frame and a lower frame, and the upper frame is configured to be detachably attached to the lower frame.

20. The system according to claim 19, wherein the flexible boot is detachably attached to the upper frame.

21. The system according to claim 20, wherein the bonding membrane is removably attached to the lower frame.

22. A system according to claim 19, wherein the flexible boot and the bonding membrane are positioned between the upper frame and the lower frame and compressed by the upper frame and the lower frame, and the flexible boot and the bonding membrane form a watertight seal between the upper frame and the lower frame.

23. The system according to claim 19, wherein the bonding membrane is held at a predetermined position between the upper frame and the lower frame.

24. The system according to claim 16, wherein the frame includes a first opening on the side of the frame configured to contact the patient's skin.

25. The system according to claim 24, wherein the bonding membrane is attached to the frame and covers only the first opening.

26. The system according to claim 24, wherein the bonding membrane includes a bag and is configured to be placed inside the ultrasonic medium container so as to cover the first opening.

27. The system according to claim 26, wherein the frame further includes a second opening opposite to the first opening.

28. The system according to claim 27, wherein the bag is configured to rest on the edge of the frame defining the second opening.

29. The system according to claim 1, wherein the binding membrane comprises a biocompatible material configured to bind the ultrasonic medium container and the ultrasonic medium to the patient's skin with minimal or no trapped bubbles.

30. The system according to claim 29, wherein the binding film comprises silicone polyurethane, polystyrene copolymer, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyrate), poly(phosphatine), polyester, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl methyl acrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, and polybutylene. A system comprising a thermoplastic elastomer selected from the group consisting of polystyrene, polybutadiene, polystyrene-ethylene-butadiene-styrene, aliphatic polyester, glycerol, poly(amino acid), coply(ether-ester), polyalkylene oxalate, polyamide, poly(iminocarbonate), polyalkylene oxalate, polyoxaester, polyorthoester, polyphosphazene, and copolymers, block copolymers, homopolymers, mixtures, and combinations thereof.

31. The system according to claim 29, wherein the bonding film has a thickness between 2 mm and 4 mm.

32. The system according to claim 29, wherein the bonding film has a thickness between 2.5 mm and 3.5 mm.

33. The system according to claim 29, wherein the bonding film contains 10% to 80% by weight of oil.

34. The system according to claim 29, wherein the bonding film contains 40% to 60% by weight of oil.

35. The system according to claim 29, wherein the bonding film has a tensile strength of >0.2 MPa.

36. The system according to claim 29, wherein the bonding membrane further comprises a membrane frame positioned along the edge of the bonding membrane.

37. The system according to claim 36, wherein the membrane frame is configured to interface with the ultrasonic medium container.

38. The system according to claim 5, wherein the fluid system is configured to deliver the ultrasonic medium to the ultrasonic medium container at a flow rate of 1 liter / min to 10 liters / min.

39. The system according to claim 5, wherein the fluid system is configured to maintain the dissolved oxygen level in the ultrasonic medium at less than 40%.

40. The system according to claim 5, wherein the fluid system is configured to maintain the temperature of the ultrasonic medium between 10°C and 30°C.

41. The system according to claim 1, wherein the binding film is configured to stretch by 200 to 500%.

42. The system according to claim 1, wherein the binding film is configured to stretch by 200 to 3000%.

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