Ultrasonic coupling system for histotripsy, and the system, method, and device thereof.

Abstract

A histotripsy therapy system configured for the treatment of tissue, which may include any number of features, is provided. Systems and methods that provide effective, non-invasive and minimally invasive therapeutic, diagnostic, and research procedures are provided herein. Additional embodiments herein provide a coupling system for histotripsy, which includes various reservoirs or ultrasound medium containers (UMCs) and coupling constraints configured to interface with the reservoirs or UMCs during histotripsy procedures.

Description

[[Technical Field]]

[0001] Claim of Priority

[0001] This patent application claims priority to U.S. Provisional Patent Application No. 63 / 519,141 filed on August 11, 2023, entitled "ULTRASOUND COUPLING SYSTEMS FOR HISTOTRIPSY AND SYSTEMS, METHODS, AND DEVICES THEREOF", which is hereby incorporated herein by reference in its entirety.

[0002] Incorporation by Reference

[0002] All publications and patent applications mentioned in this specification are herein incorporated 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 novel high intensity therapeutic ultrasound (HITU) systems configured to generate 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 transducers, drive electronics, positioning robotics, imaging systems, coupling systems, and integrated treatment planning and control software for performing comprehensive treatment and therapy of a patient's soft tissue. [[Background Art]]

[0004]

[0004] Histotripsy or pulsed ultrasonic cavitation therapy is a technique in which extremely short, powerful bursts of acoustic energy induce controlled cavitation (microbubble formation) within a focal volume. The violent expansion and collapse of these microbubbles mechanically homogenize the cellular and tissue structures within the focal volume. This is a very different end result from the coagulation necrosis characteristics of thermal delamination. To operate within the non-thermal histotripsy region, it is necessary to deliver the acoustic energy in the form of high-amplitude acoustic pulses with a low duty cycle.

[0005]

[0005] Compared to conventional focused ultrasound techniques, histotripsy has several key advantages: 1) the destructive process at the focus is mechanical and not thermal; 2) cavitation appears bright on ultrasound imaging, thereby confirming correct targeting and localization of treatment; 3) the tissue being treated appears darker (less echogenic) on ultrasound imaging, not always but generally, so that the operator can see what has been treated; and 4) histotripsy presents lesions in a controlled and precise manner. It is important to emphasize that, unlike thermal dissection techniques such as microwave, radio frequency, high-intensity focused ultrasound (HIFU), cryo, or radiation, histotripsy relies on the mechanical action of cavitation for tissue destruction and does not rely on heat, cold, or ionizing energy. [Overview of the project] [Problems that the invention aims to solve]

[0006]

[0006] This disclosure is directed toward histotripsy and various related systems, methods, and devices, and more specifically toward linked systems or subsystems (used interchangeably throughout) suitable for use in histotripsy and various related systems, methods, and devices. [Means for solving the problem]

[0007]

[0007] The present disclosure describes a coupling system or subsystem including an ultrasonic medium container or reservoir for histotripsy. The container or reservoir may include a frame body, a coupling thin film, and at least one of a plurality of constraint connectors, or a frame support bracket, or both.

[0008]

[0008] The frame body includes an upper frame body portion that defines an upper frame cavity and a lower frame body portion that defines a lower opening. A connecting thin film is partially connected to the lower frame body portion and extends across the lower frame opening. The connecting thin film seals the upper frame cavity and / or the lower frame opening. Constraint connectors are intermittently arranged around the outside of the frame body. The constraint connectors are configured to releasably secure constraint members to the frame body. Multiple constraint connectors may extend upward and outward from the lower frame body portion.

[0009]

[0009] The upper frame body portion may include an upper frame side wall extending between the upper edge and the lower edge of the side wall, and the interior of the upper frame side wall defines the upper frame cavity. The circumference of the upper edge of the side wall may be larger than the circumference of the lower edge of the side wall, forming an upper frame body that defines a frustoconical shape.

[0010]

[0010] The upper frame body portion may include a support column configured to connect the ultrasonic medium container to a mechanical support arm. The support column defines a shape body that extends outward from the outside of the upper frame body portion.

[0011]

[0011] The frame body may further include one or more frame fasteners configured to lock the lower frame body portion into the upper frame body portion. Each fastener may include a fastener base fixed to the outside of the upper frame body portion, a fastener latch fixed to the outside of the lower frame body portion, a fastener handle rotatably connected to the fastener base, and a connecting rod connecting the fastener handle to the fastener latch. The frame fasteners are configured to transition between a locked position and an unlocked position.

[0012]

[0012] In some embodiments, one or more frame fasteners are adjustable frame fasteners configured to adjust the gap distance between the upper frame and the lower frame. The gap distance can be adjusted to accommodate thin films of various thicknesses.

[0013]

[0013] The container or reservoir may include a frame support bracket configured to connect the frame body to a mechanical support arm to stabilize the position of the ultrasound medium container or reservoir. In some embodiments, the container or reservoir may be stabilized in position relative to the patient by the support bracket.

[0014]

[0014] The frame support bracket may include a central bracket portion and one or more support wings extending from the central bracket portion, the one or more support wings following the outer circumference of the upper frame body. The outer shelf portion of the upper frame body portion may rest on the upper surface of one or more wings.

[0015]

[0015] The central bracket portion may include two or more inner tabs extending inward from its inner surface. The two or more inner tabs are spaced apart to define a tab cavity between them and an inner cavity shelf portion above the tab cavity. The inner tabs, tab cavity, and inner cavity shelf portion of the central bracket portion are configured to engage with the support columns of the upper frame body portion.

[0016]

[0016] The central bracket portion may also include one or more outer tabs extending outward from its outer surface. One or more outer tabs are configured to mate and engage with a separate mechanical support arm.

[0017]

[0017] One or more support wings may include first and second support wings. In some embodiments, the first support wing may extend circumferentially from a first side of the central bracket portion around the upper frame body portion. The first support wing may extend between a first fixed end and a first free end and have a first central wing portion positioned between them. The first central wing portion may be thinner than at least one of the first fixed end, the first free end, or both.

[0018]

[0018] In some embodiments, the second support wing may extend circumferentially from the second opposite side of the central bracket portion around the upper frame body portion. The second support wing may extend between the second fixed end and the second free end and have a second central wing portion positioned between them. The second central wing portion may be thinner than the second fixed end, the second free end, or at least two of both.

[0019]

[0019] The disclosure also describes an ultrasound therapy system including at least a coupling assembly, an ultrasound therapy transducer, and a robotic positioning arm. The ultrasound therapy transducer is configured to provide ultrasound therapy when at least partially submerged in the acoustic coupling medium of an ultrasound medium container. The robotic positioning arm is coupled to the ultrasound therapy transducer. The robotic positioning arm is configured to move the ultrasound therapy transducer relative to the patient within the ultrasound medium container while maintaining an acoustic coupling with the patient via the acoustic coupling medium.

[0020]

[0020] The coupling assembly may include an ultrasonic medium container, an acoustic coupling medium, and a constraint member. The constraint member may include holes. The ultrasonic medium container may include a frame body that defines a frame cavity, which is sealed with a coupling thin film and configured to receive the coupling medium therein. Multiple constraint connectors may extend from the outside of the frame body to attach the constraint member to the frame body, particularly through holes. The frame body may also include a frame support bracket attached to the outer surface of the frame body, which is configured to stabilize the position of the ultrasonic medium container relative to the patient when fixed to a mechanical support arm.

[0021]

[0021] Methods for acoustically coupling an ultrasound therapy system to a patient before treatment are also described. In some embodiments, the method includes, in no particular order, placing an ultrasound medium container configured to receive an acoustic coupling medium over the patient, locking the ultrasound medium container in place, adding the acoustic coupling medium to the container, and introducing an ultrasound therapy introducer into the container or medium.

[0022]

[0022] In some embodiments, a method of acoustically coupling an ultrasound therapy system to a patient before treatment includes placing an ultrasound medium container configured to receive an acoustic coupling medium on the patient, the ultrasound medium container including a frame body which includes an upper frame body portion that defines an upper frame cavity and a lower frame body portion that defines a lower frame opening. A coupling thin film is partially connected to the lower frame body portion and extends across the lower frame opening. The coupling thin film seals the upper frame cavity and / or the lower frame opening. The ultrasound medium container may further include at least one of a plurality of constraint connectors extending from the outer surface of the frame body, a frame support bracket fixed to the outer surface of the frame body, or both.

[0023]

[0023] In some embodiments, a method of acoustically coupling an ultrasound therapy system to a patient prior to treatment comprises locking an ultrasound medium container in position relative to the patient for optimal acoustic coupling.

[0024]

[0024] In some embodiments, a method of acoustically coupling an ultrasound therapy system to a patient prior to treatment comprises adding an amount of acoustic coupling medium to an ultrasound medium container sufficient to submerge an ultrasound therapy transducer in the ultrasound medium container and bring a coupling membrane into contact with a portion of the patient's skin.

[0025]

[0025] In some embodiments, a method of acoustically coupling an ultrasound therapy system to a patient prior to treatment comprises introducing an ultrasound therapy introducer into a medium to form an acoustic coupling therebetween.

[0026]

[0026] The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] [Figure 1A]

[0027] It is a diagram of an ultrasonic diagnostic imaging and therapy system. [Figure 1B] It is a diagram of an ultrasonic diagnostic imaging and therapy system. [Figure 2]

[0028] It is a diagram of at least one embodiment of a histotripsy therapy and imaging system with a coupling system. [Figure 3A]

[0029] It is a side view of a coupling assembly as described in at least one embodiment. [Figure 3B]

[0030] It is a perspective view of an upper frame body of the coupling assembly of FIG. 3A as described in at least one embodiment. [Figure 3C]This is a side view of the upper frame body of the connecting assembly shown in Figure 3A, as described in at least one embodiment. [Figure 3D] This is a bottom view of the upper frame body of the connecting assembly shown in Figure 3A, as described in at least one embodiment. [Figure 3E]

[0031] This is a perspective view of the lower frame body of the connecting assembly shown in Figure 3A, as described in at least one embodiment. [Figure 3F] This is a top view of the lower frame body of the connecting assembly shown in Figure 3A, as described in at least one embodiment. [Figure 3G] This is a cross-sectional side view of the lower frame body of the connecting assembly shown in Figure 3A, as described in at least one embodiment. [Figure 4A]

[0032] Each is a side view of one or more constraint connectors of at least one embodiment. [Figure 4B] Each is a side view of one or more constraint connectors of at least one embodiment. [Figure 4C] Each is a side view of one or more constraint connectors of at least one embodiment. [Figure 4D] Each is a side view of one or more constraint connectors of at least one embodiment. [Figure 4E] Each is a side view of one or more constraint connectors of at least one embodiment. [Figure 5A]

[0033] These are side views of each of the frame fasteners in an open configuration as described in at least one embodiment. [Figure 5B] This is a side view of each of the frame fasteners in a closed configuration as described in at least one embodiment. [Figure 6]

[0034] This is a side view of a connecting assembly as described in at least one embodiment. [Figure 7A]

[0035] This is a perspective view of a frame support bracket as described in at least one embodiment. [Figure 7B] This is a top view of a frame support bracket as described in at least one embodiment. [Figure 7C] This is a side view of a frame support bracket as described in at least one embodiment. [Figure 8A]

[0036] This is a perspective view of the upper frame body including the frame support brackets shown in Figures 7A-7C, as described in at least one embodiment. [Figure 8B] This is a side view of the upper frame body including the frame support brackets shown in Figures 7A-7C, as described in at least one embodiment. [Figure 8C] This is a bottom view including the frame support brackets shown in Figures 7A-7C, as described in at least one embodiment. [Figure 9A]

[0037] This is a side perspective view of a connecting assembly including a frame support bracket in an upright configuration as described in at least one embodiment. [Figure 9B]

[0038] This is a side perspective view of the upper frame including the support bracket in an inverted configuration as described in at least one embodiment. [Figure 9C] This is a side perspective view of the upper frame including the support bracket in an inverted configuration as described in at least one embodiment. [Figure 10A]

[0039] This figure illustrates several embodiments of thin-film constraints. [Figure 10B] This figure illustrates several embodiments of thin-film constraints. [Figure 10C] This figure illustrates several embodiments of thin-film constraints. [Figure 11]

[0040] This is a perspective view of a connected assembly including thin-film constraints as described in at least one embodiment. [Modes for carrying out the invention]

[0028]

[0041] This disclosure is directed towards histotripsy and various related systems, methods, and devices, and more specifically, towards linked systems or subsystems (used interchangeably throughout) suitable for use in histotripsy and various related systems, methods, and devices.

[0029]

[0042] The histotripsy systems, methods, and devices of this disclosure may be used for non-invasive acoustic cavitation in extracorporeal, endoscopic, or fully percutaneous, surgical, minimally invasive (laparoscopic and percutaneous), robotic surgery (integrated into robotically capable medical systems), endoscopic, or fully percutaneous, for the treatment of healthy, diseased, and / or damaged tissue, including but not limited to tissue destruction, cutting, skeletonizing, and detachment. Furthermore, due to its tissue selectivity, histotripsy may be used to create a cytoskeleton that enables subsequent tissue regeneration, either newly or through the application of stem cells and other auxiliary means. Finally, histotripsy may be used to induce the release of delivered agents, such as chemotherapy and immunotherapy, by locally inducing the release of these agents by applying acoustic energy to a target. As described below, the acoustic cavitation system may include a variety of subsystems, including carts, therapy, integrated imaging, robotics, coupling, and software. The histotripsy system may also comprise a variety of other components, auxiliary devices, and accessories, including but not limited to computers, cables and connectors, networking devices, power supplies, displays, drawers / storage, doors, wheels, and various simulation and training tools. All systems, methods, devices, systems (or subsystems), and means for producing / controlling / delivering histotripsy are deemed to be part of this disclosure, including any new related inventions disclosed herein.

[0030]

[0043] Figure 1A illustrates the histotripsy system 100 according to this disclosure as a whole, comprising one or more devices or subsystems described herein, such as a therapeutic transducer 102, an imaging system 104, a display and control panel 106, a robotic positioning arm 108, and a cart 110. The devices and subsystems can be configured in various combinations to perform various methods of histotripsy, also provided herein. The system may further include an ultrasonic coupling interface and a coupling medium source (Figure 2).

[0031]

[0044] Figure 1B is a bottom view of the therapy transducer 102 and the imaging system 104. As shown, the imaging system 104 can be positioned at the center of the therapy transducer 102. Nevertheless, other embodiments may include an imaging system positioned at other locations within the therapy transducer, or possibly directly integrated with the therapy transducer. In some embodiments, the imaging system 104 is configured to produce real-time imaging at the focus of the therapy transducer 102. The system also allows multiple imaging transducers to be placed within the therapy transducer to provide multiple views of the target tissue simultaneously and integrate these images into a single 3D image.

[0032]

[0045] The histotripsy system may comprise one or more of various subsystems, including a therapeutic subsystem capable of generating, applying, focusing, and performing acoustic cavitation / histtripsy through one or more therapeutic transducers; an integrated imaging subsystem (or connection thereto) enabling real-time visualization of the treatment site and histotripsy effect throughout the procedure; a robotics positioning subsystem for mechanically and / or electronically steering the therapeutic transducers, which may further be capable of connecting to / supporting or interacting with a coupling subsystem to enable acoustic linkage between the therapeutic transducers and the patient; a system and computer-based control system (and other external systems); and software for communicating with, controlling, and interfaceing with various other components, assistive devices and accessories, including one or more user interfaces and displays and associated induction workflows, all of which function partially or together. The system may further comprise various fluid engineering and fluid management components, including pumps, valves and flow control, temperature and degassing control, and without limitation, water injection and suction capabilities, as well as supplying and storing fluids. The system may also comprise various power supplies and protective devices.

[0033]

[0046] As described above, the histotripsy system may include integrated imaging. However, in other embodiments, the histotripsy system may be configured to interface with a separate imaging system such as a C-arm, fluoroscope, cone-beam CT, or MRI to provide real-time imaging during histotripsy therapy. In some embodiments, the histotripsy system may be made to be sized to fit inside a C-arm, fluoroscope, cone-beam CT, or MRI, and may be configured to fit inside such a system.

[0034] cart

[0047] The cart 110 can be configured as a whole in various schemes and form factors based on specific intended use and procedures. In some cases, the system may comprise a number of carts configured in similar or different arrangements. In some embodiments, the carts may be configured and arranged for use in a radiological environment, and optionally in conjunction with imaging (e.g., CT, cone-beam CT and / or MRI scans). In other embodiments, the carts may be arranged for use in operating rooms and sterile environments for invasive or laparoscopic and endoscopic applications, or in robot-enabled operating rooms, and may be used alone or as part of a surgical robot procedure in which the surgical robot performs specific tasks before, during, or after the use of the system and the implementation of acoustic cavitation / histotomy. Accordingly, and depending on the procedure environment based on the embodiments described above, the carts may be positioned to provide ample workspace and access to various anatomical locations of the patient (e.g., torso, abdomen, flanks, head and neck, etc.), as well as to provide workspace for other systems (e.g., anesthesia carts, laparoscopic towers, surgical robots, endoscopic towers, etc.).

[0035]

[0048] The cart may also work with the patient's surface (e.g., a table or bed) to allow the patient to be presented and repositioned in a great many positions, angles, and orientations, including allowing changes to be made pre-operative, perioperative, and post-operative. The cart may further have the ability to interface and communicate with one or more external imaging or image data management and communication systems, not limited to ultrasound, CT, fluoroscopy, cone-beam CT, PET, PET / CT, MRI, optics, ultrasound, and image fusion and / or image flow of one or more modalities, and to support a procedure and / or usage environment, including physical / mechanical interoperability (e.g., compatibility within a cone-beam CT workspace for collecting pre-histotripsy, pre- and post-histotripsy, and / or post-histotripsy imaging data), and to provide access to and display of patient medical data, including but not limited to laboratory and historical medical record data.

[0036]

[0049] In some embodiments, one or more carts may be configured to operate together. For example, one cart may comprise a bedside mobile cart equipped with one or more robotic arms corresponding to a therapy transducer and a therapy generator / amplifier, while companion carts operating with and away from the patient may comprise integrated imaging and console / display for controlling robots and therapy facets similar to surgical robots and master / slave configurations.

[0037]

[0050] In some embodiments, the system may comprise multiple carts, all slaves to one master cart, each equipped to perform acoustic cavitation procedures. In some arrangements and in some cases, one cart configuration may allow for the storage of specific subsystems at a distance that reduces the disruption of the operating room, while another cooperating cart may essentially house bedside subsystems and components (e.g., implementation systems and therapies).

[0038]

[0051] A great many sorting and configurations of cart designs can be envisioned, and these examples do not limit the scope of this disclosure.

[0039] histotripsy

[0052] Histotripsy employs short, high-amplitude, focused ultrasonic pulses to generate a dense, active “bubble cloud” capable of targeted tissue division and destruction. Histotripsy has the ability to produce controlled tissue erosion when directed at tissue interfaces, including tissue / fluid interfaces, as well as well-bounded tissue division and destruction at subcellular levels when histotripsy targets large amounts of tissue. Unlike other forms of dissection, including thermal and radiation-based modalities, histotripsy does not rely on heat, cold, or ionizing (high) energy to treat tissue. Instead, histotripsy uses acoustic cavitation generated at the focus to mechanically influence tissue structure, potentially causing the tissue to liquefy, float, dissolve, and / or break down into subcellular components.

[0040]

[0053] Histotripsy can be applied in various forms, including: 1) Intrinsic threshold histotripsy: A pulse is delivered with a high amplitude inverse / extension phase pressure of 1-2 periods that exceeds the intrinsic threshold for cavitation in the medium (e.g., approximately 24-28 MPa for aqueous soft tissue). 2) Shock scattering histotripsy: A pulse of 3-20 periods is typically delivered within the duration. The shock waves (positive / compression phase) scattered from the initial individual microbubbles generated form inverse shock waves that structurally interfere with the incoming inverse / extension phase, forming a high amplitude inverse / dilute phase that exceeds the intrinsic threshold. In this way, a cluster of cavitating microbubbles is generated. The amplitude of the extension phase of the pulse is sufficient to cause bubble nuclei in the medium to undergo inertial cavitation within the focal zone throughout the duration of the pulse. These nuclei invert the incident wave and scatter the incident shock wave that structurally interferes with the incident wave, exceeding the threshold for intrinsic nucleation. 3) Boiling histotripsy: A pulse of approximately 1–20 ms is employed during the duration. The absorption of the impacted pulse rapidly heats the medium, thereby lowering the threshold of the intrinsic nucleus. When this intrinsic threshold coincides with the peak negative pressure of the incident wave, boiling bubbles are generated at the focus.

[0041]

[0054] The high pressure generated at the focus creates a cloud of acoustic cavitation bubbles exceeding a certain threshold, causing localized stress and tension within the tissue, as well as mechanical collapse without significant heat accumulation. At pressure levels where cavitation is not generated, minimal effects are observed in the tissue at the focus. This cavitation effect is only observed at pressure levels significantly higher than those defining the inertial cavitation threshold in water for similar pulse durations, with peak negative pressures of approximately 10 to 30 MPa.

[0042]

[0055] Histotripsy can be performed in numerous ways and under different parameters. Histotripsy can be performed entirely non-invasively by acoustically coupling a focused ultrasound transducer to the patient's skin and delivering acoustic pulses through the skin to the focal zone (treatment zone and site) through the tissues above (and intervening) it. While the application of histotripsy is not limited to percutaneous approaches, it can be applied through any means that allows contact of the transducer with tissue, including percutaneous and robotically bridging surgical procedures between open surgery and laparoscopic surgery. Assuming that the bubble cloud generated by histotripsy can be visible as a highly dynamic echo region on B-mode ultrasound images, for example, enabling continuous visualization through its use (and associated procedures), it can be further targeted, planned, directed and observed under direct visualization via ultrasound imaging. Similarly, treated and dissected tissues exhibit dynamic changes (typically reductions) in echoes that can be used to evaluate, plan, observe and monitor the treatment.

[0043]

[0056] Generally, in histotripsy therapy, an ultrasonic pulse with one or more acoustic periods 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 initiated, slightly dispersed bubbles (or a single bubble). This is called the "shock scattering mechanism."

[0044]

[0057] This mechanism relies on one (or several slightly dispersed) bubbles initiated in the initial negative half-period of the pulse at the transducer's focus. Then, a cloud of microbubbles is generated by pressure-releasing backscattering of the high-peak positive shock wavefront from these slightly initiated bubbles. These backscattered high-amplitude tenuous waves exceed the intrinsic threshold, thus creating a localized, high-density bubble cloud. Each subsequent acoustic period then induces further cavitation by backscattering from the bubble cloud surface, causing it to grow towards the transducer. As a result, a stretched, high-density bubble cloud, growing along the acoustic axis opposite to the direction of ultrasonic propagation, is observed in 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 periods and the amplitude of the positive shock. Without at least one strong shock wavefront induced by nonlinear propagation, a high-density bubble cloud would not be generated when the negative half-period of the peak falls below the intrinsic threshold.

[0045]

[0058] When ultrasonic pulses of less than two cycles are applied, shock scattering can be minimized, and the formation of dense bubble clouds depends on the negative half-cycle of the applied ultrasonic pulse that exceeds the "intrinsic threshold" of the medium. This is called the "intrinsic threshold mechanism."

[0046]

[0059] This threshold can be in the range of 26-30 MPa for soft tissues with high water content, such as human tissue. In some embodiments, using this intrinsic threshold mechanism can make the spatial extent of lesions well-defined and more predictable. At peak negative pressures (P-) not significantly higher than this threshold, subwavelength reproducible lesions can be generated that are only about half the size of the transducer's -6 dB beamwidth.

[0047]

[0060] Using high-frequency histotripsi pulses results in smaller minimum reproducible lesion sizes, which is beneficial for applications requiring precise lesion generation. However, high-frequency pulses are more susceptible to attenuation and aberrations, making treatment at greater penetration depths (e.g., deep tissue dissection) or through highly aberration-prone media (e.g., transcranial procedures or procedures where pulses are transmitted through bone) uncertain. Furthermore, histotripsi can be applied in conjunction with low-frequency "pump" pulses (typically <2 periods and having frequencies between 100 kHz and 1 MHz) and high-frequency "probe" pulses (typically <2 periods and having frequencies greater than 2 MHz or extending between 2 MHz and 10 MHz), and the peak negative pressures of the low and high-frequency pulses structurally interfere to exceed the intrinsic threshold of the target tissue or medium. Low-frequency pulses, which are tolerant of attenuation and aberrations, can raise the peak negative pressure (P-) level in a region of interest (ROI), while high-frequency pulses, which offer higher precision, can precisely pinpoint target locations within the ROI and raise the peak negative pressure (P-) above the intrinsic threshold. This approach is sometimes called "dual-frequency," "dual-beam histotripsy," or "parametric histotripsy."

[0048]

[0061] Additional systems, methods, and parameters for performing optimized histotripsy using various parameters enabling impact scattering, intrinsic thresholds, and frequency compounding and bubble manipulation are included herein as part of the systems and methods disclosed herein, including additional means for controlling the histotripsy effect such as those relating to steering and positioning the focus and simultaneously managing tissue effects (e.g., constant-focus thermal incidental injury) at or within the treatment site. Furthermore, various systems and methods that may include multiple parameters such as, but not limited to, frequency, operating frequency, center frequency, pulse repetition frequency, pulse, burst, number of pulses, period, pulse length, pulse amplitude, pulse duration, delay, burst repetition frequency, set of the former, loops of many sets, loops of many and / or different sets, sets of loops, and various combinations or arrangements thereof are included herein as part of the disclosure, including future conceivable embodiments thereof.

[0049] Therapeutic components

[0062] The therapeutic subsystem can operate in conjunction with other subsystems to produce, optimize, deliver, visualize, monitor, and control acoustic cavitation, also referred herein and hereafter as “histtripsy” and its derivatives, including boiling histotripsy and other high-frequency ultrasonic approaches to heat. It is noted that the inventions of the disclosure may also further benefit from other acoustic therapies that do not involve cavitation, mechanical, or histotripsy components. Among other features, the therapeutic subsystem may include an ultrasonic therapeutic transducer and pulse generator system configured to deliver ultrasonic pulses to tissue.

[0050]

[0063] To produce and deliver histotripsy and histotripsy derivatives, the therapeutic subsystem may also include components including, but not limited to, one or more function generators, amplifiers, therapeutic transducers, and power supplies.

[0051]

[0064] Therapeutic transducers can comprise a single or multiple elements configured to be excited by high-amplitude electrical pulses (>1000V, or any other voltage that may be harmful to the body). The amplitude required to drive the therapeutic transducer for histotripsy varies depending on the transducer design, the material 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 elements are formed using piezoelectric polymer composite materials or solid piezoelectric materials. Furthermore, the piezoelectric material can be of polycrystalline / ceramic or single-crystal components. In some embodiments, the transducer elements can be formed using silicon using MEM techniques, including CMUT and PMUT designs.

[0052]

[0065] In some embodiments, the function generator may include a field-programmable gate array (FPGA) or other suitable function generator. The FPGA may consist of parameters previously disclosed herein, including but not limited to frequency, pulse repetition frequency, burst, and number of bursts, where a burst may include pulses, number of pulses, pulse length, pulse duration, delay, burst repetition frequency, or duration; a set of bursts may include a parameter set; a loop set may include various parameter sets with or without delays, and various time delays, and independently controlled, and a number of loop sets of various combinations and sorts of such as, and throughout, may be repeated and / or new loop sets may be introduced.

[0053]

[0066] In some embodiments, the generator or amplifier may be a general-purpose single-period or multi-period pulse generator and may be configured to support driving via Class D or inductive drive and across all conceivable clinical applications and operating environments, which will be discussed in part later in this disclosure. In other embodiments, the Class D or inductive current driver may be configured to further provide step-up / down components and, optionally, preferably, enable amplitude step-up, a transducer and / or automatic transducer drive circuit. These may also have inherent protective features to further support the system and provide the ability to protect other components of the system (e.g., therapeutic transducers and / or amplifier circuit components) and / or the user from a variety of threats, including but not limited to electrical safety threats that may potentially lead to the operating environment, the system and the therapeutic system, and harm, adverse effects or problems to the user.

[0054]

[0067] The disclosed generator may enable and support the ability of the system to select, vary, and control a variety of parameters (through an effective software tool), including but not limited to those previously disclosed, as well as the ability to start / stop therapy, set and read voltage levels, pulse and / or burst repetition frequencies, number of cycles, duty cycle, effective channels and delays, modulate pulse amplitude on a fast time scale independent of the high voltage source, and / or perform other services, diagnostic or therapeutic features.

[0055]

[0068] In some embodiments, the therapeutic subsystem and / or its components, such as amplifiers, may have further integrated computer processing capabilities and may be networked, connected, accessible, and / or removable / portable, modular, and / or interchangeable between systems, and / or driven / commanded by / by other systems, or in various combinations. Other systems may include other acoustic cavitation / histtripsy, HIFU, HITU, radiotherapy, radio frequency, microwave, and cryoablation systems, navigation and positioning systems, invasive surgery, laparoscopy, single-incision / single-port, endoscopic and non-invasive surgical robots, laparoscopy or surgical towers with other energy-based or vision systems, surgical system racks or booms, imaging carts, and the like.

[0056]

[0069] In some embodiments, one or more amplifiers may comprise a Class D amplifier and associated drive circuit equipment including a matching network component. Depending on the electrical impedance of the transducer element and the selection of the matching network component (e.g., an LC circuit made from 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 circuit components used, including the drive MOSFET / IGBT transistor, the matching network component or inductor, and the transducer or autotransformer, and may typically be in the low kV range (e.g., 1–3kV).

[0057]

[0070] Therapeutic transducer elements are excited with an electrical waveform having an amplitude (voltage) sufficient to produce a pressure output for histotripsy therapy. The excitation field can be defined as the required waveform voltage per unit thickness of the piezoelectric element. For example, a piezoelectric element operating at 1 MHz is half the thickness of an equivalent 500 kHz element, so it will require half the voltage to achieve the same electric field and surface pressure.

[0058]

[0071] The therapy subsystem may also include therapy transducers of various designs and working parameters to support use in various procedures (and procedures in various settings). The system may consist of one or more therapy transducers, one or more of which may be further interchangeable and can operate with various aspects of the system in similar or different ways (for example, they may interface with a robotic arm using common interfaces and interchangeable features, or conversely, be adapted to operate with application-specific imaging probes, each of which may interface with and integrate with therapy transducers in a specifically different way).

[0059]

[0072] Therapeutic transducers can consist of various parameters, including size, shape (e.g., rectangular or circular, anatomically curved housing, etc.), geometric shape, focal length, number of elements, size of elements, distribution of elements (e.g., number of rings and ring size in annular pattern transducers), frequency, and electron beam steering that enables them. Transducers can be made from various materials (e.g., piezoelectric, silicon, etc.), form factors and types (e.g., machined elements, chip-based, etc.), and / or by various methods of their manufacture.

[0060]

[0073] Transducers can be designed and optimized for clinical applications (e.g., abdominal tumors, peripheral vascular diseases, fat removal, etc.) and desired outcomes (e.g., acoustic cavitation / histotolypse without burns to interstitial tissues), as well as to provide a broad range of applications including relatively shallow and superficial targets (e.g., thyroid or mammary nodules) and deeper or more difficult-to-reach targets such as central liver or brain tumors. They can be configured to enable acoustic cavitation / histotolypse under various parameters and sets, such as those enabled by the aforementioned system components (e.g., function generators and amplifiers, etc.), including but not limited to frequency, pulse repetition rate, pulses, number of pulses, pulse length, pulse duration, delay, repetition, synchronization delay, synchronization duration, synchronization pulse, synchronization pulse delay, various loop sets, and others, and their sortings. Transducers can also be designed to enable activation of drug payloads accumulated in tissues through various means, including injection, replacement, or delivery in micelles or nanostructures.

[0061] Integrated imaging

[0074] The disclosed system may include various imaging techniques that enable the user to visualize, monitor, and collect / use feedback on the patient's anatomical structure, areas of interest and treatment / procedure sites, and surrounding and intervening tissues in order to evaluate, plan, and perform procedures, and to adjust treatment parameters as necessary. The imaging techniques may include various ultrasound, X-ray, CT, MRI, PET, fluoroscopy, optical, contrast or agent-enhanced versions, and / or various combinations thereof. It is further disclosed that various image processing and characterization techniques may also be utilized to provide 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 the user to identify, define, and be informed of various modes of using imaging during a procedure, such as side-by-side, toggling, overlay, 3D reconstruction, segmentation, registration, multimodal image fusion, image flow, and / or displayed on various system user interfaces and displays. Examples, without limitation, may include identifying one or more significant structures (e.g., tumor drainage lymphatic vessels or vascular structures, or tumors near organ encapsulation or underlying organs) in the context of each other, such as blood vessels, tubes, nerves, ureters, fissures, encapsulations, tumors, tissue trauma / injury / disease, other organs, connective tissues, and / or identifying potential therapeutic sites within, on, and / or surrounding areas, organ systems, organs or tissues of interest.

[0062]

[0075] The system may be configured to include onboard integrated imaging hardware, software, sensors, probes, and wetware, and / or to communicate and interface with external imaging and image processing systems. Furthermore, the aforementioned components may be integrated into a therapeutic subsystem component of the system, including probes, imaging arrays, or similar, and may be electrically, mechanically, or electromechanically integrated into a therapeutic transducer. This can partially provide the ability to perform geometrically aligned imaging and therapy, where the therapy is directly in the field of view and, in some cases, aligned with the imaging. In some embodiments, this integration can constitute a fixed orientation of context-adapted imaging capability (e.g., imaging probe) to the therapeutic transducer. In other embodiments, the imaging solution may have the ability to move or adjust its position, including modifying other parameters such as angle, range (e.g., distance from the therapeutic transducer or patient), rotation (e.g., imaging plane in the case of an ultrasound probe), and / or dynamically moving / adjusting while actively imaging. The imaging component or probe may be encoded in such a way that its orientation and position relative to another aspect of the system, such as a therapeutic transducer and / or a robot-compatible positioning component, can be determined.

[0063]

[0076] In one embodiment, the system may further include an onboard ultrasound system configured to allow the user to visualize, monitor, and receive feedback about the treatment site through a system display and software, including 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 (e.g., by hand or using a robot-enabled imager), semi-automated, or fully automated means.

[0064]

[0077] In some embodiments, imaging feedback and monitoring may include monitoring changes in various combinations thereof, including backscattering from bubble clouds, backscatter speckle reduction, backscatter speckle statistics, mechanical properties of tissue (i.e., elastography), tissue perfusion (i.e., ultrasound contrast), shear wave propagation, acoustic emission, electrical impedance tomography, and / or other forms of imaging (e.g., CT or MRI) that are displayed or integrated with these.

[0065]

[0078] In some embodiments, imaging including feedback and monitoring from backscatter from bubble clouds can be used as a method to immediately determine whether a histotripsy process has been initiated, properly maintained, or possibly extinguished. For example, this method allows for the continuous monitoring of drug delivery, tissue erosion, and similar processes in real time. The method can also provide feedback that allows the histotripsy process to be initiated at a high intensity and maintained at a much lower intensity. For example, backscatter feedback can be monitored by any transducer or ultrasound imager. By measuring feedback from a therapeutic transducer, an accessory transducer can be configured to emit interrogation pulses or passively detect cavitation. Furthermore, the nature of the feedback received can be used to adjust acoustic parameters (and associated system parameters) to optimize drug delivery and / or tissue erosion processes.

[0066]

[0079] In some embodiments, imaging, including feedback and monitoring from backscatter, and speckle reduction may be configured in the system.

[0067]

[0080] In systems with feedback and monitoring via backscattering, and as a background means, when the tissue is gradually mechanically subdivided, in other words, homogenized, rendered unviable, or corroded, this process results in changes in the size and distribution of acoustic scattering. At some point in the process, the size and density of scattered particles are reduced to a level where ultrasound is hardly scattered, or the amount scattered is significantly reduced. This results in a significant reduction of speckle, which is a coherent constructive and destructive interference pattern of bright and dark areas seen in an image when a coherent illumination source, in this case ultrasound, is used. After some treatment time, the speckle reduction results in dark areas within the treatment volume. The amount of speckle reduction is related to the amount of tissue subdivision and therefore may be related to the size of the remaining tissue fragments. When this size is reduced to a level smaller than cells, it is not assumed that cells are surviving. Thus, treatment can proceed until the desired level of speckle reduction is achieved. Speckle is readily visible and evaluated on standard ultrasound imaging systems. Specialized transducers and systems, including those disclosed herein, may also be used to evaluate backscattering changes.

[0068]

[0081] Furthermore, in systems with speckle-mediated feedback and monitoring, as well as as a background means, the image persists and changes little from frame to frame, provided that the scattering distribution does not change and there is no movement of the object being imaged. Nevertheless, the scattering can change enough to be detected by signal processing and other means well before it is reduced to a size sufficient to cause speckle reduction. This group of techniques can act as detectors of speckle statistical changes. For example, the size and location of one or more specks in an image begin to decorrelate before observable speckle reduction occurs. Speckle decorrelation, after appropriate motion compensation, can be a highly sensitive measure of the mechanical unviability of tissue and therefore a measure of the efficacy of therapy. This feedback and monitoring technique can enable early observation of changes resulting from acoustic cavitation / histotopsis processes and can identify tissue changes (e.g., the occurrence of erosion) before substantial or complete tissue effects. In one embodiment, this method may be used to monitor acoustic cavitation / histtripsy processes for enhanced drug delivery when the treatment site / tissue is to be temporarily rendered unsustainable and tissue damage / erosion is undesirable. In other embodiments, this may include speckle decorrelation by the movement of scattering in an increasingly fluidized therapeutic volume, for example, when partial or complete tissue erosion is desired.

[0069]

[0082] In systems with feedback and monitoring via elastography, and as a background measure, when the treatment site / tissue is further subdivided (homogenized, rendered unsustainable, or corroded) for each acoustic cavitation / histotomy effect, its mechanical properties change from a soft but interconnected solid to a mucus or paste with little long-range interaction. These changes in mechanical properties can be measured by various imaging techniques, including MRI and ultrasound imaging systems. For example, ultrasound pulses can be used to generate forces (i.e., radiant forces) on localized volumes of tissue. Tissue responses (displacement, tension, and velocity) can be significantly altered during histotripsy treatment, allowing the state of tissue unsustainability to be determined by imaging or other quantitative means.

[0070]

[0083] The system can also incorporate feedback and monitoring via changes in shear wave propagation. As a background measure, tissue repartitioning makes the tissue more fluid and less solid, and fluid systems generally do not propagate shear waves. Thus, the degree of tissue fluidization provides an opportunity for feedback and monitoring of the histotripsy process. For example, ultrasound and MRI imaging systems can be used to observe shear wave propagation. The disappearance of such waves in the volume being treated can be used as a measure of tissue destruction or inviolability. In one system embodiment, the system and support subsystems can be used to generate and measure interacting shear waves. For example, two adjacent ultrasound foci may affect tissue by pushing the tissue in a particular manner. If the adjacent foci are in a fluid, the shear waves will not propagate to interact with each other. If the tissue is not fluidized, the interaction should be detected by external means, for example, by the difference frequency which is detected only when two shear waves interact nonlinearly, and the disappearance of the wave correlates with tissue damage. Therefore, the system can be configured to use this modality to enhance feedback and monitoring of acoustic cavitation / histopexy procedures.

[0071]

[0084] In systems with feedback and monitoring via acoustic emission, as well as as a background means, when tissue volume is subdivided, its effect on acoustic cavitation / histtripsy (e.g., bubble cloud here) changes. For example, bubbles may grow larger, have different lifetimes, and disrupt the changing properties of intact and fluidized tissue. Bubbles may also migrate and interact after tissue subdivision, creating larger bubbles or synergistic interactions between bubbles, all of which can produce changes in acoustic emission. These emissions can be heard during treatment and change during treatment. Analysis of these changes, and their correlation with the efficacy of the therapy, can enable monitoring of the progress of the therapy and may be configured as a feature of the system.

[0072]

[0085] In systems with feedback and monitoring via electrical impedance tomography, and as a background means, it is possible to generate an impedance map of the therapy site based on the spatial electrical properties throughout the therapy site. Imaging of the conductivity or dielectric constant of the patient's therapy site can be inferred from performing surface electrometry. Conductive electrodes are attached / bonded 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 the surface, and the voltage is measured at several points using the electrodes. The process can be repeated for different configurations of the applied current. The resolution of the resulting image can be adjusted by changing the number of electrodes employed. A measure of the electrical properties of the therapy site within the skin surface can be obtained from the impedance map, and changes in acoustic cavitation / histtripsy (e.g., specifically bubble clouds) and their location, as well as the histotripsy process, can be monitored using this as configured in the system and support subsystems.

[0073]

[0086] Through the system software, user interface, and display, users may be able to further select, annotate, mark, highlight, and / or outline various areas of interest or treatment sites, as well as predefined treatment targets (on images) that can be used to instruct and direct the system to image, test, and / or treat the areas to be treated. In some configurations, users may perform procedures using manual ultrasound probes (e.g., diagnostic handheld probes). In other configurations, the system may perform procedures as directed and / or automated by the system using robotic and / or electromechanical positioning systems, or conversely, the system may allow a combination of manual and automated use.

[0074]

[0087] The system may further include the ability to perform image registration, including the registration of imaging and image datasets to enable the system's navigation and localization to a patient, including treatment sites (e.g., tumors, serious structures, anatomical structures of bone, anatomical structures and their distinguishing features). In one embodiment, the system enables a user to image and identify an area of ​​interest, such as the liver, using integrated ultrasound, and to select and mark a tumor (or its surrogate marker) contained within the liver through / displayed in the system software, the system registers the image data in a coordinate system defined by the system, and the system's therapy and robotics subsystems further enable the delivery of synchronized acoustic cavitation / histotopsy to the marked tumor. The system may have the ability to register various image sets, including those previously disclosed, with respect to each other and to provide navigation and localization (e.g., therapy transducers to the images and therapy transducers to CT or MRI / ultrasound fusion images with robotics subsystem tracking).

[0075]

[0088] The system may also be capable of operating in a variety of interventional endoscopic and surgical environments, including independently, and in conjunction with or equipped with various optical imaging capabilities (e.g., fiber and / or digital) and other systems (surgical / laparoscopic towers, vision 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-sensing, ultrasound-enabled, etc.)). The disclosed system may be configured to operate with these systems, and in some embodiments, it may operate together with them, or in other embodiments, all or part of the system may be integrated into the above systems / platforms (e.g., acoustic cavitation / histtripsy-enabled endoscopic systems or laparoscopic surgical robots). In many of these environments, the therapeutic transducer may operate, for example, during or around the time of use of optically guided endoscopes / bronchoscopes, or, as another example, with laparoscopic robots (e.g., Intuitive Da The Vinci*Xi system may be used when browsing / manipulating a tissue / treatment site. Furthermore, these embodiments and examples may 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 segment or lobe of the lung in preparation for acoustic cavitation / histotolipssis via non-invasive transthoracic treatment (e.g., with the transducer placed externally on / around the patient)). The systems disclosed herein may also comprise all or part of these subsystem hardware packaged within the other system carts / consoles / systems described herein (e.g., acoustic cavitation / histotolipssis systems and / or subsystems integrated and operated from the navigation or laparoscopic systems described above).

[0076]

[0089] The system may also be configured through various aforementioned parameters and other parameters to spatiotemporally display real-time visualization of the bubble cloud, including tissue effects resulting from the treatment phase / post-treatment from tissue / bubble cloud interactions, and the system can dynamically image, visualize, and display the bubble cloud and any changes to the bubble cloud (e.g., decreasing or increasing echogenicity), which may include intensity, shape, size, location, morphology, persistence, etc. These features can enable the user to track and follow the treatment in real time and continuously within a single integrated procedure and interface / system, and to verify the safety and efficacy of the treatment in operation (for other interventions or surgical modalities that require numerous steps to achieve the same thing, or when the treatment effect is not visible in real time (e.g., radiotherapy), or when such as (e.g., real-time visualization of local tissue during thermal dissection) is not achievable, and / or when other procedures further require invasive approaches (e.g., incisions or holes) and repeated imaging in a scanner between procedure steps (e.g., CT or MRI scans)). The systems, subsystems, components, modalities, features, and usage workflows / methods of the above disclosure may be implemented without limitation through hardware, software, user interfaces, and usage environments, and any resulting data, as well as any means of using such data for analytics, artificial intelligence, or digital health applications and systems, as well as any future improvements, enhancements, and inventions in this area, are also considered to be within the scope of this disclosure.

[0077] Robotics

[0090] The system may comprise a variety of robotic subsystems and components, including, but not limited to, one or more robotic arms and controllers, which may further operate in conjunction with other subsystems or components of the system for delivering and monitoring acoustic cavitation / histtripsy. As previously discussed herein, the robotic arms and control systems may be integrated into one or more cart configurations.

[0078]

[0091] For example, one system embodiment may include an integrated robotic arm and control system, as well as a cart with therapy, integrated imaging, and software, where the robotic arm and other mentioned subsystems are controlled by the user through a single bedside cart form factor.

[0079]

[0092] 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 cart, the robot-enabled cart being located on the bed / patient side and the master being located away from the cart.

[0080]

[0093] The disclosed robotic arm may include multiple joints, segments, and degrees of freedom, and may also include various integrated sensor types and encoders implemented for various uses and safety features. Sensing techniques and data may include, for example, vision, potentiometers, position / localization, kinematics, force, torque, speed, acceleration, dynamic loading, and / or others. In some cases, sensors may be used for a user to direct robot commands (e.g., to gesture to the robot to a preferred setup position or to dock at home). Further details regarding the robotic arm can be found in U.S. Patent Publication No. 2013 / 0255426 to Kassow et al., which is disclosed herein by reference in whole.

[0081]

[0094] The robotic arm receives control signals and commands from a robotic control system that may be housed in a cart. The system may be configured to provide a variety of functions, including but not limited to position, tracking, pattern, triggering, and event / action.

[0082]

[0095] 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.

[0083]

[0096] Tracking may be configured to include time-controlled tracking and / or distance-controlled tracking.

[0084]

[0097] The movement pattern may be configured to include intermediate positions or points, and a sequence of positions along a predefined path in space.

[0085]

[0098] The trigger may be configured to include a variety of sensory means, including distance measuring means, time, and / or those disclosed herein, but not limited to visual / imaging-based force, torque, localization, energy / power feedback, and / or others.

[0086]

[0099] Events / actions may be configured to include a variety of examples, such as proximity-based events (approaching / moving away from a target object), activation or deactivation of various end-effectors (e.g., therapeutic transducers), starting / stopping / pausing sequences of the above events, triggering or switching between triggers of events / actions, starting and changing / toggle movement patterns, and / or time-based and transient events spanning defined tasks and spatiotemporal space.

[0087]

[0100] In one embodiment, the system includes a three-degree-of-freedom robot positioning system that allows the user to microscopically position the therapeutic transducer through the X, Y, and Z coordinate systems (through the system's software and associated user interface), and the overall macroscopic positioning of the transducer (e.g., aligning the transducer over the patient's body) is completed manually. In some embodiments, the robot may have six degrees of freedom, including X, Y, Z, as well as pitch, roll, and yaw. In other embodiments, the robot subsystem may have further degrees of freedom, allowing the robot arm support base to be positioned along a linear axis running parallel to the overall direction of the patient surface, and / or the support base height to be adjusted up and down, and allowing the position of the robot arm to be corrected relative to the patient, patient surface, cart, linking subsystem, additional robot / robot arm, and / or additional surgical systems, including but not limited to surgical towers, imaging systems, endoscopic / laparoscopic systems, and / or others.

[0088]

[0101] One or more robotic arms may also be equipped with various features to assist in manually or semi-manually manipulating and correcting the arm position, and these features may interface on or between the therapeutic transducer and the most distal joint of the robotic arm. In some embodiments, the features are configured to include a handle that enables manipulation and manual control by one or more hands. The handle may also be configured to include user input and electronic control features of the robotic arm (e.g., activating or deactivating a free-drive mode) for commanding various drive capabilities or modes to actuate the robot to assist in the overall or fine positioning of the arm. The workflow for the initial positioning of the robotic arm and therapeutic head can be configured to allow the therapeutic transducer / head to be positioned first in the coupling solution, with the therapeutic transducer interfaced directly with the arm, or, in a different workflow, to allow the user to set up the coupling solution first, with the robotic arm interfaced with the therapeutic transducer / coupling solution as a later / final setup step.

[0089]

[0102] In some embodiments, the robotic arm may comprise a robotic arm on a laparoscope, single-port, endoscope, a hybrid or combination thereof, and / or other robot, and the robot in the system may also be a slave to a master controlling the arm and potentially multiple other arms, equipped to simultaneously perform other tasks (such as visualizing, imaging, grasping, cutting, tying, sealing, closing, stapling, dissecting, suturing, marking, etc.) including operating one or more laparoscopic arms (and instruments) and various histotripsy system components. For example, the laparoscopic robot may be used to prepare the surgical site, including manipulating the position of the organ to provide more ideal acoustic access and, optionally, further stabilizing the organ to minimize respiratory movement. In conjunction with and in parallel with this, a second robotic arm may be used to deliver non-invasive acoustic cavitation through body cavities, such as observed under real-time imaging from a therapeutic transducer (e.g., ultrasound) and by simultaneously occurring visualization via a laparoscopic camera. In other related embodiments, similar approaches combining endoscopy and non-invasive approaches, as well as further combining endoscopy, laparoscopy, and non-invasive approaches, may be used.

[0090] software

[0103] The system may feature a variety of software applications, features, and components that enable users to interact with, control, and use the system for a wide range of clinical applications. The software may communicate with and work with one or more subsystems, including but not limited to therapeutic, integrated imaging, robotics, and other components, as well as assistive devices and accessories for the system.

[0091]

[0104] Overall, in no particular order of importance, the software is responsible for initializing and setting up the system, servicing the system, communicating and importing / exporting / storing data, modifying / operating / configuring / controlling / commanding various settings and parameters by the user, mitigating safety and usage-related risks, planning procedures, supporting various transducer configurations, robotic arm and drive systems, function generator and amplifier circuits / slaves, test and therapeutic ultrasound sequences, transducer steering and positioning (electromechanical and electron beam steering, etc.), treatment patterns, imaging and imaging probe support, their manual and electromechanical / robot-responsive movement, imaging support for measuring / characterizing various dimensions within or around the procedure and treatment site (e.g., depth from one anatomical location to another), in It can provide features and support for performing pre-procedure assessments and protocols to measure / characterize the nature and state of situ treatment sites (e.g., acoustic cavitation / histotolypse threshold and its heterogeneity), target setting and target alignment, calibration, marking / annotating, localizing / navigating, registering, guiding, providing and guiding, providing communication tools (video, audio, sharing, etc.), troubleshooting, instructions, warnings, alerts, and / or enabling communication through various networking devices and protocols, under direct observation and viewing with real-time imaging such as displayed through software that includes various views and viewports for autonomous, autonomous but browsing.The software user interface and support display may include a variety of buttons, commands, icons, graphics, text, etc., that enable the user to interact with the system in a user-friendly and effective manner, and these may be presented in an unlimited number of arrangements, layouts, and designs, and may include two or more displays (e.g., a touchscreen monitor and a touchpad), and / or may be networked to one or more external displays or systems (e.g., another robot, navigation system, system tower, console, monitor, touch display, mobile device, tablet, etc.), and may be displayed in a similar or different style or set of features of the system.

[0092]

[0105] The software, as part of a typical system including one or more computer processors, can support various aforementioned function generators (e.g., FPGAs), amplifiers, power supplies, and therapeutic transducers. The software may be configured to allow the user to select, determine, and monitor various parameters and settings of acoustic cavitation / histtripsy, and to allow the user to stop / start / modify the above parameters and settings upon observing / receiving feedback on performance and status.

[0093]

[0106] The software may be configured to allow the user to select from a list or menu of numerous transducers and to support automatic detection of the transducers upon connection to the system (and verification of appropriate sequence and parameter settings based on the selected application). In other embodiments, the software may update target and amplifier settings (e.g., channels) based on the specific transducer selection. The software may also provide transducer recommendations based on pre-treatment and planning inputs. Conversely, the software may provide the user with error messages or warnings if the selection or parameters of the therapeutic transducers, amplifiers, and / or function generators are incorrect or result in errors or failures. This may further include reporting details and locations of such errors.

[0094]

[0107] In addition to the above, the software may be configured to allow users to select treatment sequences and protocols from a list or menu and store selected and / or previously selected sequences and protocols so as to be associated with specific clinical use or patient profiles. Associated profiles may include any associated patient, procedure, clinical and / or engineering data, which may be used to inform, modify and / or guide current or future treatments or procedures / interventions, whether as decision support (e.g., using sequential datasets to build and guide new treatments) or as an active part of the procedure itself.

[0095]

[0108] As part of the plan or during treatment, the software (and working with other components of the system) can enable the user to evaluate and test acoustic cavitation / histtripsy thresholds at various locations within a user-selected region of interest or a predefined treatment area / volume to determine a minimum cavitation threshold throughout the region or area / volume, ensuring that treatment parameters are optimized to achieve, maintain, and dynamically control acoustic cavitation / histtripsy. In one embodiment, the system allows the user to manually evaluate and test threshold parameters at various points. These points may include points at the predefined boundaries of the selected region of interest and treatment area / volume, within the boundaries, and at central locations / positions, 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, such as enabled by the robotics subsystem described above, where the user can instruct a robot or the robot may be commanded to perform measurements autonomously.

[0096]

[0109] The software may also be configured to enable various sortings of delivering and positioning optimized acoustic cavitation / histtripsy in and through a selected area / volume by working with a computer processor, as well as one or more function generators, amplifiers, and therapeutic transducers. This may include, but is not limited to, systems comprising various combinations including fixed / natural focus placement using pure electromechanical positioning configurations, electron beam steering (with or without electromechanical positioning), electron beam steering to a new 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 dynamically varying one or more acoustic cavitation / histtripsy parameters based on the aforementioned ability to update therapeutic parameters based on threshold measurements (e.g., dynamically adjusting amplitude across a therapeutic area / volume).

[0097] Other components, auxiliary devices, and accessories

[0110] The system may comprise a variety of other components, auxiliary equipment and accessories, including but not limited to computers, computer processors, power supplies including high-voltage power supplies, controllers, cables, connectors, networking devices, security, communications, software applications for integration into information systems including hospital information systems, cellular communication devices and modems, handheld wired or wireless controllers, goggles or glasses for advanced visualization, augmented or virtual reality applications, cameras, sensors, tablets, smart devices, telephones, Internet of Things capabilities, special use "apps" or user training materials and applications (software or paper-based), virtual proctors or trainees and / or other enabling features, devices, systems or applications, and / or methods of using the foregoing.

[0098] System variations and methods / applications

[0111] In addition to performing a wide range of procedures, the system can enable users to benefit from additional advantages such as enhanced planning, imaging, and guidance. In one embodiment, the system can enable users to create patient, target, and specific-use treatment plans, and the system may be configured to optimize treatment parameters based on feedback to the system during planning, and planning may further include the ability to perform various test protocols to gather unique inputs to the system and the plan.

[0099]

[0112] The feedback can include various parameters such as energy, power, location, position, organization, and / or other parameters.

[0100]

[0113] The system and the feedback described above may also be further configured and used to autonomously (and robotically) deliver optimized treatment plans and protocols, such as those visualized under real-time imaging during the procedure, allowing the user to directly observe the local therapeutic tissue effects as the treatment progresses, and to start / stop / modify the treatment at the user's discretion. Both test and treatment protocols may be updated during the procedure at the user's direction, or based on logic built into the system in some embodiments.

[0101]

[0114] Many of these benefits can further improve other forms of acoustic therapy, including thermal dissection by high-intensity focused ultrasound (HIFU) and high-intensity therapeutic ultrasound (HITU), including boiling histotripsy (thermal cavitation), and are also recognized as part of this disclosure. This disclosure also considers the application of histotripsy as a means of activating previously delivered active drug payloads that are inactive, either by protection in micelles, nanostructures or similar protective structures, or through molecular arrangements that enable activation only when acoustic energy is applied.

[0102]

[0115] In another embodiment, a therapeutic subsystem comprising one or more amplifiers, transducers, and power supplies may be configured to enable numerous acoustic cavitation and histotripsy driving capabilities, resulting in unique benefits based on application, method, and / or patient-specific use. These benefits may include, but are not limited to, the ability to better optimize and control therapeutic parameters that enable electron beam steering and / or other features, along with the delivery of more energy, along with a more desirable thermal profile, increased treatment speed, and reduced treatment time.

[0103]

[0116] This disclosure also includes novel systems and concepts such as systems and subsystems comprising a new and "general-purpose" amplifier capable of enabling a number of drive approaches (e.g., single and multi-period pulse generation). In some embodiments, this may include a variety of novel features to further protect the system and user in terms of electrical safety or other threats (e.g., adverse effects on transducers and / or amplifier circuit equipment).

[0104]

[0117] In another embodiment, the system and therapy subsystem may include a very large number of therapy transducers, which may be configured for specific applications and uses, adaptable to therapies across a wide range of working parameters (such as target size, depth, and location), and may include a wide range of working specifications (detailed below). The transducers may be further adapted, interfaced, and connected to robot-enabled systems, as well as to coupling subsystems that allow the transducer to be positioned in or with an acoustic coupling device that enables simultaneous imaging and histotripsy therapy through an acceptable acoustic window in many embodiments. The therapy transducer may also be equipped with an integrated imaging probe or localization sensor that has the ability to display and determine the transducer position within the therapy site and provide a direct view (or representation) of the therapy site, as well as such that the appearance and intensity of acoustic cavitation / histotopsis tissue effects and bubble clouds may or may not change throughout the therapy, and depending on its location within the therapy (e.g., tumor, around healthy tissue, severe structure, fatty tissue, etc.).

[0105]

[0118] The systems, methods, and uses of the systems disclosed herein may be beneficial in overcoming important yet unaddressed needs in the areas of surgical procedures including, but not limited to, soft tissue dissection, oncology, cancer immunology, advanced image-guided procedures, laparotomy, laparoscopy, single incision, transluminal, endoscopic, non-invasive, and various combinations thereof; various intervention spaces for catheter-based procedures in vascular, cardiovascular, pulmonary, and / or neuroscience-related spaces; cosmetic / aesthetics, metabolism (e.g., type 2 diabetes), plastic surgery and reconstruction, vision and ophthalmology, orthopedics, gynecology, and human health conditions, as well as other systems, devices, and methods for treating diseased, injured, undesirable, or healthy tissues, organs, or cells.

[0106]

[0119] Systems and methods are also provided for improving the treatment pattern within tissue, which can reduce treatment time, improve efficacy, and reduce the amount of energy and constant-focus tissue heating delivered to the patient.

[0107] Usage environment

[0120] The disclosed systems, methods of use, and methods of using the systems can be performed in a great many environments and settings, with or without various support systems such as anesthesia, including but not limited to physician's offices, mobile healthcare centers or systems, automobiles and related vehicles (e.g., vans), aircraft and ships and other aerospace and maritime transport vehicles, and / or any structure capable of providing temporary procedural support (e.g., tents). In some cases, the systems and / or subsystems disclosed herein may also be provided as features integrated into other environments, such as direct integration of the histotripsy therapy subsystem into an MRI scanner or patient surface / bed, where at least the therapy generator and transducer are integrated into such a system, and in other cases, the histotripsy configuration further includes a robotic positioning system which may be further integrated into a scanner or bed-centered design.

[0108] Link

[0121] The system may include various coupling subsystem embodiments enabled and configured to allow acoustic coupling to the patient to provide effective acoustic access for ultrasound visualization and acoustic cavitation / histopepsis (e.g., providing an acoustic window and medium between the transducer and the patient, and supporting it). These may include different form factors of such as open and closed device solutions, as well as several arrangements that may be configured to allow dynamic control over the acoustic medium (e.g., temperature, oil-soluble gas contents, particulate filtration level, sterility, volume, components, etc.). Such dynamic control components may be directly integrated into the system (in the cart) or may be located in separate devices and / or outside the cart, but in transient / intermittent or continuous communication with the system.

[0109]

[0122] The coupling subsystem typically includes at least a coupling medium (e.g., degassed water or aqueous solution), a reservoir / container for holding the coupling medium, and a support structure (including interface to other surfaces or devices). In most embodiments, the coupling medium is water, which may be conditioned before or during treatment (e.g., cooled, degassed, filtered, etc.). Various conditioning parameters may be employed depending on the system configuration and its intended use / application.

[0110]

[0123] Reservoirs or ultrasonic medium containers (UMCs) can be formed and shaped in various sizes and shapes to fit / conform to a patient, allowing therapeutic transducers to engage / access and work within the acoustic medium for each defined and required working space (such as the minimum volume of medium to allow therapeutic transducers to be positioned and / or move through one or more therapeutic positions or patterns and at various standoffs or depths from the patient), and the reservoir or medium container may also mechanically support the load and load distribution through the use of mechanical and / or electromechanical support structures. Typical examples include support frames. Containers may also be of various shapes, sizes, curvatures, and dimensions and may be formed from various material components (single, multiple, composite, etc.) which may vary throughout. In some embodiments, the container or reservoir may include insertable and removable features, and / or fabricated therein, such as films, drapes, thin films, blowers, etc., which may be used to conform to the patient and assist in confining / filling the medium within the container. The container or reservoir can further incorporate various sensors (e.g., volume / fill level), drainage (e.g., inlet / outlet), lighting (e.g., LED), markings (e.g., filling line, setup orientation, etc.), text (e.g., labeling), and more.

[0111]

[0124] In one embodiment, the reservoir or medium container includes a sealable frame in which a thin film and / or film may be placed to provide a comfortable means of contact with the reservoir (later comprising a treatment head / therapy transducer) as an interface to the patient, further providing a barrier to the medium (e.g., water) between the patient and the therapy transducer. In other embodiments, the thin film and / or film may include an opening, the edge in which the patient contacts, which provides a fluid / mechanical seal to the patient, but in contrast, directly allows for medium communication with the patient (e.g., a direct degassed water interface with the patient). The superstructure of the reservoir or medium container in both of these examples may further provide a proximal portion (e.g., the top) of the structure that will be open or enclosed (e.g., to prevent spillage or to give additional features).

[0112]

[0125] The thin films of disclosure may be formed from various elastic materials, viscoelastic polymers, thermoplastics, thermoplastic elastic materials, thermosetting polymers, silicon, urethane, rigid / flexible copolymers, block copolymers, random block copolymers, etc. The materials may be hydrophilic, hydrophobic, surface-modified, coated, extracted, etc., and may further contain various additives to enhance performance, appearance, or stability. In some embodiments, the thermoplastic elastic material may be styrene-ethylene-butylene-styrene (SEBS) or other similar strong, flexible elastic materials. The thin film form factor may be flat or pre-formed before use. In other embodiments, the thin film may be inelastic (i.e., convex) and can be pressed against the patient's skin to acoustically couple a transducer to tissue. Systems and methods for controlling the level of contaminants (e.g., particulate matter, etc.) on the thin film to maintain an appropriate level of ultrasonic coupling are further disclosed. Too much particulate matter or contaminants may cause ultrasonic scattering. This may be achieved with a removable film or coating on the outer surface of the thin film to protect from contamination.

[0113]

[0126] The above material may be formed into a useful thin film through molding, casting, spraying, ultrasonic spraying, extrusion, and / or any other processing method that produces a useful embodiment. The above material may be single-use or reposable / reusable. The above material may be non-sterile, antimicrobially clean, or sterile, and sterilization can be carried out using any known method, including but not limited to ethylene oxide, gamma, e-beam, autoclavation, steam, hydrogen peroxide, plasma, chemicals, etc. The thin film may be further configured with an outer molded or overmolded frame to provide mechanical stability to the thin film during handling, including assembly, setup, and disassembly of linked subsystems. Various parameters of the thin film, including thickness, thickness profile, density, and manufacturing method (e.g., polymer molecular weight and copolymer ratio, additives, plasticizers, etc.), can be optimized for this use, including optimizing in particular to maximize acoustic transmission properties, including minimizing ultrasonic imaging artifacts, including but not limited to impact on the cavitation onset threshold and / or thin film reflections, as a typical example.

[0114]

[0127] An open reservoir or media container may include various methods of filling, including using a pre-prepared media or water that can be delivered to the container to a predefined specification (such as temperature and gas saturation levels), or it may include additional features integrated into the design that enable filling and draining (e.g., ports, valves, hoses, tubes, fittings, bags, pumps, etc.). These features may be further configured to interface with, or into, other devices, such as a fluid engineering system. In some cases, the fluid engineering system may be an in-hospital media preparation system in a hospital or medical environment room, or conversely, a mobile cart-based system capable of preparing and transporting media from a cart to a media container.

[0115]

[0128] Enclosed iterations of a reservoir or media container may include various features for sealing, in some embodiments sealing to the proximal / top part or structure of the reservoir / container, or in other cases, the sealing may include embodiments sealing features on the transducer or transducer housing. Furthermore, some embodiments may include dynamic capabilities to control the volume of fluid within these designs, minimize the possibility of air bubbles or turbulence in the fluid, and allow changes in the focal length to a target area without moving the transducer. Thus, integrated features and controls enabling fluid communication may be provided, some of which include the ability to monitor and control the various fluid parameters disclosed above (the ability to supply / remove fluid on demand). To provide this functionality, the entire system, and as a part thereof, the linked subsystem may include a fluid conditioning system which may include various electromechanical devices, systems, power, sensing, computing, pumping, filtering, and control systems. The reservoir may also be configured to receive signals that deform or change its shape in a specific and controlled manner to allow the target point to be adjusted without moving the transducer.

[0116]

[0129] The linked support system may include various mechanical support devices for interface the reservoir / container and medium to the patient and workspace (e.g., bed, floor, etc.). In some embodiments, the support system comprises a mechanical arm with three or more degrees of freedom. The arm may have a proximal interface to one or more locations (and features) of the bed, including but not limited to frames, rails, customized rails or inserts, as well as one or more distal locations of the reservoir or container. The arm may also be a feature realized on one or more carts, the carts may consist of various unrestricted arrangements, and in some cases the carts may have only the role of supporting and providing the disclosed support structure.

[0117]

[0130] In some embodiments, the support structure and arm may be implemented as a standalone cart or as a robot-enabled arm integrated into a cart further comprising two or more system subsystems, or the robot-enabled arm may be the arm of another robot of an interventional, surgical, or other type, further comprising various user input features and / or coupling solution features (e.g., filling, draining, etc.) for operating / controlling the robot arm (e.g., located in / within a coupling medium). In some examples, the support structure robot arm position encoder may be used to coordinate the operation of a second arm (e.g., comprising a therapy transducer / treatment head), such as by positioning the therapy transducer at a desired / known location and placing it within the coupling support structure.

[0118]

[0131] Overall, significant unaddressed needs exist today within interventional and surgical medical procedures across a variety of procedures, including those that utilize minimally invasive devices and approaches to treat disease and / or injury, where unaddressed needs may be resolved entirely by novel medical procedures. The capabilities of today's medical systems are often limited by access, making less invasive or non-invasive approaches preferable, or the tools of today lack the ability to deliver preferred / requested tissue effects (e.g., working around / through severe structures without serious injury), or the physical setup of the system makes certain procedural approaches less desirable or impossible, and combinations of approaches, along with treatments affecting enhanced tissue, can enable entirely novel procedures and approaches that are not possible today.

[0119]

[0132] In addition, there is a unique need to enable histotripsy delivery, including robotic histotripsy delivery, and one or more histotripsy therapy transducers may be configured to acoustically couple to a patient using a completely sealed approach (e.g., no acoustic media communication with the patient's skin), and to allow one or more histotripsy transducers to be moved within the coupling solution without interfering with the movement / route of the robotic arm or interfering with / disrupting the coupling interface, which could affect the intended treatment and / or target location.

[0120]

[0133] As a non-limiting example, histotripsy acoustic and patient-connected systems and methods for enabling histotripsy therapy / treatment in any setting, such as intervention suites, operating rooms, hybrid suites, imaging centers, medical centers, office environments, mobile treatment centers, and / or others, are disclosed herein. The following disclosures further describe novel systems used to create, control, maintain, modify / enhance, monitor, and set up / deconstruct acoustic and patient-connected systems in a variety of approaches, methods, environments, architectures, and workflows. Generally, the novel systems of the disclosure can enable a coupling medium, in some cases degassed water, to interface between a histotripsy therapy transducer and a patient, the acoustic medium providing sufficient acoustic coupling to the patient to enable delivery of histotripsy pulses through a user-desired therapeutic location (and volume), the delivery may require the physical movement of the histotripsy therapy transducer within a defined workspace including the coupling medium, and the coupling system is configured to allow the above movement of the therapy transducer (and the positioning of the system, e.g., a robot) to be free and unhindered by a coupling support system (e.g., a frame or manifold holding the coupling medium).

[0121] Connecting systems and subsystems / components

[0134] The disclosed histotripsy acoustic and patient coupling system generally includes, but is not limited to, one or more of the following subsystems and components, an example of which is depicted in at least Figure 2: 1) a thin film / barrier film for providing an enclosed, sealed, and equiangular patient coupling and histotripsy system interface; 2) a frame body for holding the thin film and providing sufficient working and overhead space for the required range of motion (x, y, and z, pitch, roll, and yaw) of the histotripsy therapy transducer; 3) an ultrasonic medium of sufficient volume to provide acoustic coupling and interface to the histotripsy therapy transducer and robotic arm; 4) one or more mechanical support arms for enabling the installation, positioning, and load support of the frame body, thin film, and medium; 5) a fluid engineering system for preparing, providing, and removing the ultrasonic medium from the frame body and thin film; and 6) thin film constraints.

[0122]

[0135] In some embodiments, the coupling system may be completely sealed, while in other embodiments and configurations, the coupling system may be partially open to provide immediate access (physical and / or visual).

[0123]

[0136] The acoustic and patient coupling systems and subsystems may further include a variety of features and functions, as well as associated workflows, and may be further configured in various ways to enable histotripsy procedures as detailed below.

[0124]

[0137] Figure 2 illustrates one embodiment of the histotripsy therapy and imaging system 200, including a coupling assembly 212. As described above, the histotripsy therapy and imaging system may include a therapy transducer 202, an imaging system 204, a robotic positioning arm 208, and a fluid cart 210.

[0125]

[0138] Therapeutic and / or imaging transducers can be housed in a coupling assembly 212, which may include a reservoir or medium container 213 containing a frame body 215 and a coupling thin film 214, and a thin film constraint 216 configured to prevent the thin film from expanding too far from the transducer. The coupling assembly can be filled with an acoustic coupling medium such as a fluid or gel. The thin film constraint may be, for example, a semi-rigid or rigid material configured to limit the expansion / movement of the thin film caused by the addition of the coupling medium to the coupling assembly. In some embodiments, the thin film constraint is not used, and the stretch and tensile strength of the thin film prevents expansion. The coupling thin film can be a mineral oil-injected SEBS thin film to prevent direct fluid contact with the patient's skin. In the exemplary embodiment, the coupling assembly 212 is supported by a mechanical support arm 218 that is load-bearing in the xy plane but capable of allowing manual or automated z-axis adjustment. The mechanical support arm can be mounted on the floor, a patient table, or a fluid cart 210. The mechanical support is designed and configured to align and hold the connecting thin film 214 in appropriate position relative to the patient's skin, while still allowing the movement of the therapy / imaging transducer relative to the patient and further relative to the connecting thin film 214 by the robotic positioning arm 208.

[0126]

[0139] The fluid cart 210 may include additional features, including a fluid tank 220, a cooling and degassing system, and a programmable control system. The fluid cart is configured with automated control of the fluid sequence for external loading of the linked thin film. Further details about the fluid cart are provided below.

[0127]

[0140] Figures 3A to 3G depict a reservoir or UMC (Ultrasonic Medium Container) 312, which includes at least a frame body 330 and a connecting thin film 314. As shown in Figure 3A, the frame body 330 includes an upper frame body portion 335 (shown in more detail in Figures 3B to 3D) and a lower frame body portion 360 (shown in more detail in Figures 3E to 3G). Multiple constraint connectors 364 for attaching thin film constraints (not shown in Figures 3A to 3G) to the frame body 330 can be intermittently arranged around the outside of the lower frame body 360. At least a portion of the connecting thin film 314 is housed within the lower frame body 360 and extends across the lower frame body opening 366.

[0128]

[0141] Figures 3B to 3D depict the upper frame body 335 of the connecting assembly or UMC312. The upper frame body 335 includes an upper frame side wall 340 extending between the upper side wall edge 342 and the lower side wall edge 344. The upper edge 342 may include a shelf portion 343 extending outward from the outside 335b of the upper frame body 335 (and approximately vertically) (and / or away from the upper frame cavity 346). The upper shelf portion 342 can be configured to be mounted on a frame support bracket (not shown in Figures 3A to 3G), as will be provided in more detail below. In some embodiments, the perimeter p of the upper side wall edge 342 o The circumference p of the lower edge 344 is i It may be larger and form an upper frame body 335 that defines the shape of a truncated cone or bucket.

[0129]

[0142] The interior 335a of the upper frame body 335 (and / or upper frame side wall 340) defines an upper frame cavity 346 having a height H (and / or depth) sufficient to at least partially and freely accommodate one or more transducers and connecting media, such as those described herein (and shown in Figure 2).

[0130]

[0143] The outer 335b of the upper frame body 335 includes a strut 347 configured to connect a reservoir or UMC 312 (and / or connecting assembly) to a machine support arm directly (Figure 2) or via an intermediate frame support bracket (Figures 7A to 9). The strut 347 defines a shape body that extends outward from the outer 335b of the frame body 335 (and / or side wall 340) and approximately vertically. The strut 347 may contain a strut cavity 348 within it. The strut cavity 348 is configured to receive a portion of the machine support arm and / or frame support bracket within it, and to releasably secure the reservoir or UMC (and / or connecting assembly) to the machine support arm. The strut 347 and / or strut cavity 348 do not pass through the inner 335a of the frame body 335 and are therefore not connected to the upper frame cavity 346. In some embodiments, the surface 347a of the support column 347 extends approximately perpendicular to one or more of the upper end 342, the lower end 344, and / or the upper shelf portion 343.

[0131]

[0144] The support column 347 and / or support column cavity 348 can define any shape suitable for engaging with the machine support arm and / or frame support bracket. As illustrated, in some embodiments, both the support column 347 and the support column cavity 348 can define approximately rectangular shapes. Nevertheless, in some embodiments, the support column body 347 and the support column cavity 348 can define different shapes, such as triangles, pentagons, hexagons, heptagons, octagons, circles, ellipses, and so on.

[0132]

[0145] As further illustrated in Figures 3A to 3C, the column body 347 can be reinforced with one or more reinforcing rods 349 made from a material harder than the reservoir or UMC 312 and / or the column 347 to reinforce the connection between the reservoir or UMC 312 and one or more of the machine support arms 218 or one or more frame support brackets 370. In some embodiments, the reinforcing rods 349 may be made from stainless steel. In some embodiments, the reinforcing rods 349 may be distributed symmetrically around the column 347, such as being placed at each corner of a rectangular column.

[0133]

[0146] Figures 3E to 3G depict the lower frame body 360 of the reservoir or UMC 312. The lower frame body 360 defines a lower frame body opening 366, which is covered and / or sealed by a connecting thin film. The lower frame body 360 includes a number of constraint connectors 364 and latches 352 intermittently spaced around the outside 360b of the lower frame body 360.

[0134]

[0147] As shown in at least Figure 3E, each latch 352 extends outward and downward from the outside 360b of the lower frame body 360. The latches 352 interact with latch handles 353 attached to the outside 335b of the upper frame body 335 to fasten the upper frame body 335 and the lower frame body 360 to each other, forming an assembly or UMC 312. Furthermore, as shown in at least Figure 3G, the lower frame includes several columns 355 extending outward and upward from the lower frame body 360 to assist in aligning the upper frame body 335 and the lower frame body 360 to each other. The upper frame 335 includes corresponding holes or gaps 353 for receiving the columns 355 (Figures 3B and 3D).

[0135]

[0148] As further shown in Figures 3F and 3G, the lower frame body 360 includes a lower channel or step 368 defined therein. The lower channel or step 368 surrounds the lower body frame opening 366 and is configured to receive and maintain at least one, if not all, of the gasket, thin film, or guide wall of the upper frame body.

[0136]

[0149] As shown in at least Figure 3G, each constraint connector 364 extends outward and upward from the outside 360b of the lower frame body 360. This outward and upward design allows the constraint to be attached to and / or suspended from the reservoir or UMC 312 (and / or lower frame body 360) through holes / openings in the constraint to help limit the thin film. In some embodiments, as shown in Figures 3E–3G, the constraint connector 264 defines an approximately rectangular shape with rounded or curved corners. Nevertheless, as shown in Figures 4A–4E, the constraint connector 364 can define any suitable shape, including but not limited to triangular (Figure 4A), trapezoidal (Figure 4B), circular (Figure 4C), castle-like (Figure 4D), and / or hook-like (Figure 4E).

[0137]

[0150] Figures 5A and 5B depict the frame clasp 350 in an open, i.e., unclapped position and a closed, i.e., clapped position, respectively. The frame clasp 350 includes a clasp base 351 fixed to the outside 335b of the upper frame body 335, a clasp latch 352 fixed to the outside 360b of the lower frame body 360, a clasp handle 353 swivelably connected to the clasp base 351, and a connecting rod 354 with one end connected to the handle 353 and the other end connected to the latch 352. In some embodiments, the connecting rod is threaded, such as a screw or bolt, and the handle 353 may further include a threaded receiver 535a for interacting with the threaded connecting rod 354. Adding a screw 354a to the rod 354 and receiver 535a allows for adjustment of the tension applied to the upper frame body 335 and lower frame body 360 by the fastener 350, thereby also allowing adjustment of the gap distance between the upper frame body 335 and the lower frame body 360. Non-limiting examples of suitable frame fasteners include toggle fasteners and / or latch fasteners.

[0138]

[0151] Figure 6 depicts another reservoir or UMC612, including at least a frame body 630 and a connecting thin film 614. The reservoir or UMC612 in Figure 6 is similar to the reservoir or UMC312 in Figures 3A–3G, except that the upper frame body 635 and the lower frame body 660 are integrated, and a constraint connector 664 extends upward and outward from the upper frame body 635. The reservoir or UMC612 (and / or connecting assembly) may or may not include at least one frame retainer 650.

[0139]

[0152] Figures 7A to 7C depict a frame support bracket 770 configured to be included in either a reservoir or an UMC (and / or connecting assembly) as described herein. The frame support bracket 770 includes one or more support wing portions 780, 790 extending from a central bracket portion 772. The central bracket portion 772 is configured to be fixed to and / or mated to a shaped strut 347 of the upper frame body 335, as described herein in Figures 3A to 3G.

[0140]

[0153] The central section 772 extends inward from the inner surface 772a of the central structural section 772, and includes two or more inner tabs 774, 776 spaced apart, defining a tab cavity 777 between them. The inner cavity shelf section 778 extends along the upper surface of the tab cavity 777, connecting the inner tabs 774, 776. The inner cavity shelf section 778 is configured to rest on and / or be installed on the upper surface of the formed support column 347 of the upper frame 335 in Figures 3A to 3G. When properly installed, the formed support column 347 is positioned within the tab cavity 777 sandwiched between the inner tabs 774, 776, and the inner cavity shelf section 778 is installed on the upper surface of the formed support column 347, with the outer surface 347a of the support column 347 facing and / or in contact with the inner surface 772a of the central section 772. The central portion 772 can be further secured to the support column 347 by any suitable mode of fastening, including but not limited to screws, bolts, rivets, adhesives, and the like.

[0141]

[0154] The central section 772 extends outward away from the outer surface 772b of the central structure 772 and further includes an outer tab 779 located approximately in the center of the outer surface 772b of the central section 772. The outer tab 779 is configured to attach the support bracket 770 (and / or frame body, linkage assembly, reservoir, UMC) to the machine support arm.

[0142]

[0155] As shown in Figure 7B, the outer tab 779 may be longitudinally centered between the two inner tabs 774, 776, while the outer tab 779 extends from the opposite side of the inner tabs 774, 776 of the bracket 770. The frame support bracket can define a roughly C-shaped bracket (when viewed from a top or bottom view).

[0143]

[0156] As depicted in Figure 7C, the support bracket 770 may also include a first support wing 780 and a second support wing 790. The first support wing 780 extends in a curved manner from the first side of the central bracket portion 772. The first support wing 780 extends between a first fixed end 782 and a first free end 784, and has a first central wing portion 783 positioned between them. The second support wing 790 extends in a curved manner from the second side of the central bracket portion 772. The second support wing 790 extends between a second fixed end 792 and a second free end 794, and has a second central wing portion 793 positioned between them. The first and second support wings 780, 790 are configured to extend circumferentially around the outer circumference of the upper frame body 335.

[0144]

[0157] As depicted in Figures 7A and 7C, the first central wing portion 783 may be thinner and / or shorter than one or both of the first fixed end 782 or the first free end 784. As further depicted in Figures 7A and 7C, the second central wing portion 793 may be thinner and / or shorter than one or both of the second fixed end 792 or the second free end 794.

[0145]

[0158] As further illustrated in Figure 7C, in some embodiments, the outer tab 779 of the bracket 770 may include one or more openings 795, 796 defined through it. The first outer tab lock opening 795 can be configured to receive and maintain a fastener, such as a knurled knob (see Figures 9A-9C), therein to secure the bracket 770 (and / or frame, reservoir, UMC) to a mechanical support arm (not shown in Figure 7C). The second outer tab adjustment opening 796 can be configured to receive and maintain an adjustment knob (see Figures 9A-9C) therein to adjust the tilt of the bracket 770 (and / or frame, reservoir, UMC) relative to the patient and / or mechanical support arm.

[0146]

[0159] Figures 8A–8C depict the upper frame body 835 of the reservoir or UMC (and / or connecting assembly) including the frame support bracket 870. The support bracket 870 is secured to the frame body 835 by a bracket connector 845 that extends from the outside 835b of the frame body 835 onto the frame fastener 850. The support bracket 870 is configured to reinforce and / or stabilize the position of the frame body 835 (and / or connecting assembly, reservoir, or UMC) relative to the patient, which may be important during histotripsy and / or acoustic cavitation.

[0147]

[0160] As shown in Figure 8B, the frame support bracket 870 is fixed to the frame body 835 such that the upper shelf portion 843 of the frame body 835 is mounted on the upper wall 871 of the support bracket 870. In addition, in some embodiments, the thicker free ends 884, 894 and fixed ends 882, 892 may be placed directly over intermittently spaced fasteners 850, which may be areas of the frame body 835 where greater stress is applied.

[0148]

[0161] As shown in Figure 8C, the support wings 880, 890 of the support bracket 870 wrap circumferentially around the outer circumference p of the frame body 835 (and / or assembly, reservoir, or UMC). In some embodiments, the bracket extends around about 20–75% of the outer circumference of the shelf. In some embodiments, the bracket extends around about 25–65% of the outer circumference of the shelf. In some embodiments, the bracket extends around about 30–50% of the outer circumference of the shelf.

[0149]

[0162] As further shown in Figure 8C, when properly installed, the formed support column 847 is sandwiched between the inner tabs 874 and 876 of the central bracket portion 872, and the inner surface 872a of the central bracket portion 872 abuts against the outer surface 847a of the support column 847.

[0150]

[0163] In some embodiments, the frame support bracket may be made from the same material as the frame body. In some embodiments, the frame support bracket and the frame body may be made from rigid plastic. In other embodiments, the frame support may include a stronger or higher modulus material, which may differ from the upper frame body. In particular, the frame support 770 may include polycarbonate or other high modulus polymers or plastics that enable acoustic coupling. Alternatively, metal frame support brackets may also be used.

[0151]

[0164] As further illustrated in Figure 8A, a gasket 828, such as an O-ring, may be positioned around the alignment member 837 of the upper frame body portion 835 to help seal a portion of the connecting thin film (not shown) around the alignment member 837. The gasket 828, the alignment member 837, and the portion of the connecting thin film are received within a lower channel or step of the lower frame body portion, designed to seal the cavity of the upper frame body. The upper frame 835 may include one or more alignment tabs 855 extending therefrom to further assist in properly securing the thin film onto the frame 835.

[0152]

[0165] In some embodiments, as shown in Figure 9A, the frame support bracket 970 may include first and second wing portions 980, 990 extending circumferentially around about half of the frame body 935, with the fixed end wing portions 982, 992 and the central wing portion 972 being approximately equal in thickness or height, while the free end portions 984, 994 are narrower and / or less thick and / or shorter than the rest of the bracket 970. The support bracket 970 is fixed to the frame body 935 on the inner surface of the bracket (and / or the central bracket portion 972 or the wing portions 980, 990) and fixed to the support arm handle 924 of the machine support arm 918 via the outer surface of the central bracket portion 972.

[0153]

[0166] The support arm handle 924 includes a knurled knob 925, a handle trigger 926, and a swivelable lever 927. The knurled knob 925 is configured to secure and / or lock the bracket 970 (and / or the upper frame 935, lower frame 960, reservoir 930 attached thereto) to the machine support arm 918. The knurled knob 925 includes a threaded pin 925a (dummy line) extending therefrom and designed to rotate into a tablock opening on the outside of the bracket 970 (not shown in Figures 9A-9C).

[0154]

[0167] As shown in Figures 9B-9C, the handle trigger 926 is configured to rotate the support arm handle 924 (and / or the bracket 970, upper frame 935, and reservoir attached thereto) by approximately 180 degrees when activated. For example, the first actuation of the handle trigger 926 rotates the support arm handle 924 (and / or the bracket 970, frame 935, and reservoir attached thereto) from an upright position (Figure 9A) to an upside-down position (Figures 9B-9C). In another example, the second actuation of the handle trigger 926 rotates the support arm handle 924 (and / or the bracket 970, frame 935, and reservoir attached thereto) from an upside-down position (Figures 9B-9C) to an upright position (Figure 9A). In some embodiments, the actuation of the handle trigger 926 can also allow for the rotation of a portion of the machine support arm 918.

[0155]

[0168] This rotational feature of the handle 924 may be useful in some embodiments when loading or connecting a thin film, gasket, and / or a lower frame (not shown) to the upper frame 935. For example, in the inverted position of the upper frame 935 as shown in Figures 9B–9C, the thin film can be easily mounted on the alignment member 937, and optionally, one or more (i.e., two, three, or four) holes in the thin film can be aligned with or adjacent to one or more (i.e., two, three, or four) alignment tabs 955. The outer gasket 928 can then be positioned around the thin film before the lower frame is added and fastened to the upper frame to form a reservoir or UMC. In some embodiments, an inner gasket may also be used to assist in sealing the thin film.

[0156]

[0169] The swivel lever 927 is configured to fine-tune / adjust the orientation (via tilt and / or swivel) of the connecting assembly, which includes the bracket 970, upper frame 935 and lower frame 960, and reservoir 930, to which it is attached. In some embodiments, the support arm handle 924 does not rotate via the swivel lever 927. As further shown in Figures 9B-9C, the swivel lever 927 is configured to move around the handle trigger 926 to rotate or swivel the entire connecting assembly, which includes the upper frame 935 and lower frame 960, bracket 970, and reservoir 930, to which it is attached, out-of-axis by up to 15 degrees in either direction as needed. In some embodiments, the frame support bracket may be made of a material harder than the material of the frame body. In some embodiments, the frame support bracket may be made of a metal such as stainless steel, and the frame body may be made of a hard plastic such as polycarbonate.

[0157]

[0170] Figures 10A–10C illustrate embodiments of thin-film constraints 316, 416, which are referred to herein as constraint devices. The constraint devices of this disclosure comprise a mesh structure with openings having various geometric shapes as described herein. Generally, the constraint devices are configured to provide mechanical support to the thin film when the thin film is filled with a connecting medium / fluid. In particular, the constraint devices can prevent the thin film of the reservoir or UMC from over-expanding by holding the constraint device over and around the patient and maintaining the acoustic coupling between the transducer and the patient. The constraint devices can also minimize all forces applied to the patient when the reservoir or UMC is filled with a connecting medium / fluid, thereby reducing all load transfer to the patient. The thin-film constraint 316 in Figure 10A is configured to include a portion or section that rests beneath the patient and is further configured to have one or more portions that are adapted and configured to connect to, or to, a connecting assembly, frame body, reservoir or UMC, or operating table.

[0158]

[0171] In some embodiments, the thin film constraint may include a flexible or pliable material. The constraint can be an elastomer such as silicon, rubber, or other similar material. Generally, the thin film constraint may have some pliability or stretchability. Nevertheless, in order to effectively constrain the connecting thin film when the reservoir or UMC is filled with the connecting medium, the thin film constraint should be less flexible or pliable than the connecting thin film (e.g., stiffer than the thin film).

[0159]

[0172] Referring to Figure 10A, the constraint device 316 may include a central constraint portion or section 322 and one or more peripheral constraint portions or sections 324 extending outward from the central constraint portion 322 and / or connected to the central constraint portion 322. For example, the embodiment in Figure 10A shows a constraint device 316 with a central constraint portion 322 and first and second peripheral constraint portions 324 extending from both sides of the central constraint portion. For example, as illustrated, in some embodiments, the constraint device 316 may define an hourglass shape, and / or the peripheral constraint portions may define a trapezoidal shape. The constraint device 316 may comprise two or more peripheral constraint portions, and it is assumed that each peripheral constraint portion is identical in size and shape to the others. Alternatively, one peripheral constraint portion may be larger in size than the other. In yet another embodiment, each peripheral constraint portion may have a different shape depending on whether the patient is facing right or left with respect to the histotripsy system. Combinations of both the size and shape of each peripheral constraint portion are also conceivable.

[0160]

[0173] Alternative embodiments, including a one-sided flanged configuration, are illustrated in Figure 10B. For example, the embodiment in Figure 10B shows a constraint device 416 comprising a first patient contact portion 422 and a second bulging portion 424 extending outward from the first patient contact portion 422. In this particular embodiment, the first patient contact portion 422 may be configured to include a mounting mechanism for attaching the outer portion 422a of the patient contact portion 422 to an operating table, C-arm, or other mechanical stabilizing structure. Specifically, the outer portion 422a can be attached directly to the operating table, for example, by attaching an elongated honeycomb structure to a mounting feature found on the operating table. In particular, a one-sided flanged portion configuration may be preferable for certain patients, for example, when the treatment area may be more easily accessible than if only a single flanged portion were employed. A one-sided flanged constraint device may also be useful for patients in a lateral decubitus position or perhaps for smaller patients. Note that, with the exception of a single flanged section, most other features remain similar to those shown in Figures 10A and 10C.

[0161]

[0174] Generally, the central portion or patient contact portion 322, 422 of the constraint device 316, 416 is configured to be positioned beneath the patient undergoing histotripsy or other therapeutic ultrasound procedure. For example, the constraint device can be placed on a medical or operating table, and the patient can then be positioned on the upper surface of the patient contact portion 322, 422. In other words, the constraint device 316, 422 can be positioned between the patient and the operating table. The patient's weight relative to the upper surface of the patient portion is typically sufficient to hold the thin film constraint in place during the histotripsy procedure. Nevertheless, in some embodiments, the patient contact portion 322, 422 can be temporarily or permanently attached to the medical or operating table, as will be described in more detail below.

[0162]

[0175] The peripheral constraint portions 324, 424 of the thin film constraint are configured to be attached to or coupled to the reservoir or UMC of the ultrasound therapy system, or to a coupling assembly. In some examples, as described herein, the coupling assembly 212 (Figure 2) may include the reservoir or UMC (i.e., the combined thin film and frame body) and the coupling thin film constraint. The reservoir or UMC (and / or coupling assembly) may be filled with an ultrasound coupling medium and may be placed in contact with the patient's skin to provide an acoustic coupling between the treatment head of the ultrasound system and the patient. As described herein, the coupling thin film itself may comprise flexible and elastomer materials and may expand or enlarge the coupling thin film when the reservoir or UMC is filled with the ultrasound coupling medium. If the constraint device is not in place, the volume of the coupling medium in the reservoir or UMC (e.g., 10-12 L or more) may cause excessive expansion of the thin film, which may result in leakage of the coupling medium, insufficient workspace to allow movement of the treatment head according to the treatment plan, and / or inability to properly couple the treatment head to the patient.

[0163]

[0176] In some embodiments, the peripheral constraint portions 324, 424 of the constraint devices 316, 416 may include a plurality of openings 326, 426. Similarly, the patient portions 322, 422 may also include a plurality of openings 328, 428. In some examples, the openings 326, 426 of the peripheral constraint portions and the openings 328, 428 of the patient portions may have patterns. In some embodiments, the patterns of the openings in the peripheral constraint portions may be different from the patterns of the openings in the patient portions. In other embodiments, the patterns of the openings in the patient and peripheral constraint portions may be the same. Generally, the openings in the peripheral constraint portions are configured to engage with, attach to, or interface with a reservoir or UMC via constraint connectors. For example, the reservoir or UMC may have constraint connectors having the shape or form of hooks, tabs, buttons, or other attachment features, and these constraint connectors may be connected to or attached to the openings in the peripheral constraint portions.

[0164]

[0177] In one embodiment, as shown in Figures 10A-10B, the pattern of openings 326, 426 in the periphery constraint portion may consist of a honeycomb pattern or arrangement. In some implementations, individual openings may include hexagonal shapes. Patterns including shapes with at least one interior angle, such as triangles, squares, rectangles, pentagons, trapezoids, parallelograms, and so on, may be preferred. Nevertheless, any other shapes, including circles, ovals, and other shapes including radii of curvature, can be used for the openings. Combinations of shapes are also conceivable. In some embodiments, the openings within the periphery constraint portion may have different sizes. For example, the honeycomb pattern shown in Figure 10A includes multiple smaller hexagonal openings arranged around one larger hexagonal opening. Nevertheless, in Figure 10C, the openings within the periphery constraint portion may have similar or the same size throughout the entire periphery constraint portion. The periphery portion is optimized for load distribution and support along the coronal plane of the patient. The opening in the peripheral constraint portion includes an engagement feature that can be removably connected to the constraint connector of the ultrasonic coupling assembly.

[0165]

[0178] As described above, in some embodiments, the patient portions 322, 422 may include a different opening pattern than that of the peripheral constraint portions. Generally, the openings of the peripheral constraint portions are optimized and configured for attachment to constraint connectors of the reservoir or UMC, while the openings of the patient portions are not typically attached to the reservoir or UMC. Instead, the openings of the patient portions can be optimized and configured to prioritize patient comfort, as the patient's weight is placed on the patient portions throughout the histotripsy procedure and the patient remains lying on the patient portions. In some embodiments, the opening pattern in the patient portions can be configured to reduce hot spots or pressure points. In other embodiments, the patient portions may not include any openings at all and may instead be simply rigid or flat portions of flexible material.

[0166]

[0179] With respect to Figure 10B, the outside of the patient contact portion 422a or the patient contact portion 422 may also be configured to connect to the operating table. The outside of the patient contact portion 422a may be attached to a hook or other feature that extends outward from the operating table and receives the opening of the restraint device 416. Two or more openings in the restraint device 416 may be hooked onto or attached to a table to provide enhanced safety.

[0167]

[0180] Referring further to Figures 10A and 10B, in some embodiments, the peripheral constraint portions 324, 424 may have a width w1 that is wider than the width w2 of the patient portion. As shown, the peripheral portion can bulge outwards as it extends away from the patient portion. For example, the peripheral portion may start with a width w2 that touches or connects to the patient portion and may bulge or bulge outwards to a width w1 that is greater than the width w2. In some embodiments, this bulge may be uniform, and therefore the side 332 of the peripheral constraint portion maintains a straight edge. Nevertheless, it should be understood that the side 332 may be curved, pointed, or other shapes that make it easier to attach the constraint to the reservoir or UMC (and / or frame body or connecting assembly). For example, the side 332 may be curved inwards or outwards to better conform to the patient when the peripheral portion is wrapped around the patient and attached to the reservoir or UMC. In the example of Figure 10A, the peripheral constraint portion 324 may bulge at an angle 329. For example, angle 329 may be as small as 10-15 degrees and as large as 75-90 degrees. In the illustrated example, angle 329 can be approximately 20-50 degrees, and preferably about 35 degrees. The uniform bulge of the thin film constraint in each of the peripheral constraint portions in Figure 10A gives the constraint a bow tie-like shape. It is also conceivable that two or more angles 329 or different angles for each peripheral constraint portion may be used. Alternatively, a smooth transition to a peripheral bulge such as an arc or curve is also conceivable.

[0168]

[0181] The constraint devices described herein are monolithic in structure. In some embodiments, the constraint device may be manufactured from a single sheet of polymer and produced using a die-cutting process. In other embodiments, the constraint device may be manufactured using injection molding or 3D printing. The constraint device may be provided as a transparent or translucent material such that visibility in the surgical field is optimal.

[0169]

[0182] Figure 11 illustrates one embodiment of a constraint device 1016 coupled to a reservoir or UMC 1013, with a patient 1001 lying on the patient portion 1016a of the constraint device. In particular, at least a portion of the constraint connector 1064 of the reservoir or UMC 1013 is positioned through some of the holes 1026 of the peripheral constraint portion 1024 of the constraint device 1016 to attach (i.e., suspend, hang, connect) the constraint device 1016 to the reservoir or UMC 1013. The coupling assembly 1002 in Figure 11 includes the reservoir or UMC 1013, a thin film 1014, a medium 1005, and the constraint device 1016, thereby acoustically coupling the patient to the histotripsy system and / or treatment.

[0170]

[0183] As shown in the figure, when the reservoir or UMC 1013 is filled with the ultrasonic bonding medium 1005, the bonding thin film 1014 expands. In this example, it can be seen that the rigidity of the thin film constraint 1016 relative to the bonding thin film 1014 prevents over-expansion of the bonding thin film 1014. The bulging peripheral portion 1024 of the constraint device 1016 allows the constraint device 1016 to be attached at various points along the reservoir or UMC 1013 while also maintaining a precise fit to the contours of the patient 1001. Depending on the location of the target tissue, the patient may be positioned supine, prone, or lateral. The bulging peripheral portion provides flexibility in how the constraint is attached to the reservoir or UMC, allowing for various patient positions, treatment head locations, and UMC positions.

[0171] Thin films / barrier films and related architectures

[0184] Thin films and barrier films may consist of a variety of biocompatible materials capable of enabling conformal linkage to the patient's anatomical structures with minimal or no trapped bubbles that could interfere with ultrasound imaging and histotripsy therapy, and providing a sealed barrier layer between the aforementioned patient's anatomical structures and the ultrasound medium, contained within the working space provided by the frame and assembly.

[0172]

[0185] Thin film and barrier film materials can comprise flexible and elastic biocompatible materials / polymers, such as various thermoplastics and thermosetting materials, as well as permanent or bioabsorbable polymers. Additionally, UMC frames can also comprise the same materials. In some examples, the thin film may be a pre-formed or flat rigid or semi-rigid polymer.

[0173] ultrasonic medium

[0186] As described above, the ultrasonic medium may comprise any applicable medium capable of providing sufficient and useful acoustic coupling to enable histotripsy therapy and adequate clinical imaging (e.g., ultrasound). The ultrasonic medium may include, but is not limited to, a variety of aqueous solutions / mediums, including mixtures with other soluble fluids that may have preferred or more preferred acoustic qualities, including the ability to match the speed of sound, as part of this disclosure and system. Examples of media may include defasted water, and / or mixtures / cosolutions of defasted water with various alcohols such as ethanol.

[0174] Mechanical support arms and arm architectures

[0187] Various designs and configurations of mechanical support arms (and arm architectures) may be employed to support acoustic and patient linkage systems, including providing users with an efficient and ergonomic workflow. Support arms may be configured with a range of degrees of freedom including, but not limited to, x, y, z, pitch, roll, and yaw, as well as additional interface features that may allow for additional height adjustment or translation.

[0175]

[0188] Arms can have a variety of joints and segments of different numbers and types. Typically, an arm can have at least two segments. In some configurations, an arm can have three to five segments.

[0176]

[0189] The arm is also configured to interface proximal to the main support base or base interface (e.g., robot, table, table / bed rail, cart, floor mount, etc.) and distally to the frame / assembly and the overall "UMC" or "connection solution". This specific distal interface may further include features for controlling the position / orientation of the frame / assembly within the frame / assembly interface.

[0177]

[0190] For example, in some embodiments, the arm / frame interface may include a ball-jointed wrist. In another example, the interface may include the use of a gimbal wrist or a wrist with adjustable pitch and roll control. These interfaces may further employ unique user interfaces and inputs to assist interaction with various wrists, which may include additional handles or knobs (as an unrestricted example) to further allow for the placement of UMC / coupling solutions. For example, a gimbal wrist can benefit from allowing the frame / assembly to have three degrees of freedom (independent of arm degrees of freedom), including pitch, roll, and yaw adjustments.

[0178]

[0191] The support arm, comprising a frame / assembly and an arm wrist further interfaced with it, may feature brakes, including cable-operated or electronically actuated brakes, and quick-release mechanisms that can interact with one or more axes individually or in groups. The support arm may also include an electronic lift system and base support. In some embodiments, these lift systems / base supports are located in the same place as the robot arm base, and the robot arm is equipped with a histotripsy therapy transducer configured to fit / function within an enclosed coupling solution. In other embodiments, the support arm is placed on a separate cart. In some cases, the separate cart may include a fluid mechanics system or a user console. In other embodiments, the separate cart is interfaced to a bed / table, including but not limited to rails, sides, and / or a bed / table base. In other examples / embodiments, the separate cart is interfaced to a floor base structure / foundation capable of managing weight and tipping requirements.

[0179] Fluid dynamics systems, control systems, and system architectures

[0192] As part of the overall fluid engineering management, the histotripsy system, including the acoustic / patient coupling system, may be configured to include an automated fluid engineering system, which is primarily responsible for providing a reservoir for the preparation and use of the coupling medium. The fluid system may include the ability to degas, cool, monitor, regulate, supply / fill, and remove / drain the coupling medium between the coupling frame / assembly and the coupling medium.

[0180]

[0193] The fluid system may include an emergency high-flow system for rapid filling and draining of the connecting medium from the UMC. The fluid system may be configured to fill the UMC with fluid on demand or in predetermined filling volumes (e.g., automatic filling of the current volume of fluid, such as 1L, 3L, 6L, 9L, etc.).

[0181]

[0194] In some implementations, the fluid system is configured to connect to a fluid source, such as tap water, or to receive fluid from a fluid source. The fluid system may include a degassing system or mechanism, such as a degassing thin film, which can be configured to degas the fluid as it flows from the fluid source into the fluid tank of the fluid system. The degassing system can be further configured to degas the fluid as it flows from the fluid tank into the UMC. In some implementations, the fluid is degassed up to a first degassing threshold, while the fluid tank is filled from the fluid source and held at the first degassing threshold. The fluid system can then further degas the fluid as it is transferred from the fluid tank into the UMC (e.g., up to a second degassing threshold).

[0182]

[0195] In some embodiments, the fluid engineering system can be configured for single use of the connecting medium or for reuse of the medium as an alternative. In some embodiments, the fluid engineering system can achieve positive pressure or vacuum to perform leak tests of the UMC and thin film before filling with the connecting medium. Vacuum assistance can also be used for removing air from the UMC during the filling process. The fluid engineering system may further include filters configured to prevent particulate contamination from reaching the UMC.

[0183]

[0196] The fluid engineering system may be implemented in the form of a mobile fluid engineering cart. The cart may include an input tank, a drain tank, a degassing module, a filling pump, a drain pump, an inert gas tank, an air compressor, tubing / connectors / lines, electronic and manual control systems and input devices, a power supply and one or more batteries. The cart may also optionally include a system check container / reservoir for evaluating histotripsy system performance and relational system diagnostics (configured to accommodate the required water volume and working space for therapeutic transducers).

[0184]

[0197] The cart may be powered via standard electrical service / connectors and by batteries to enable portable or off-grid use. The batteries may also provide emergency power. The cart may also be equipped with a nitrogen tank and / or air compressor (not shown) to allow for spraying of the main / drain tubing to ensure that the main / drain tubing is kept dry / clean (under a nitrogen blanket). In some examples, the cart may include various processors or electronic controllers configured to program / monitor / report water conditions and parameters. Parameters may include oxygen saturation, temperature, particulate matter residue, pH, mixing ratio, flow rate, fill level, power level / battery level, etc., and may be detected in real time by any number of sensors placed in and around the system. Parameters may be read on the fluid cart's UI screen and / or displayed / controlled on a therapy system cart display (via a software UI).

[0185]

[0198] A degassing module may include a filter or degassing film configured to remove particulate matter / debris, a degassing contactor, and a vacuum or peristaltic pump for moving fluid through the system. In some examples, the filter may have pores as small as 0.2 microns. The degassing contactor may have the ability to reduce flow to one part per billion at a flow rate of approximately 3 gallons per minute, as well as the ability to remove dissolved O2, CO2, and N2 gases. The vacuum pump may include key features such as pure transfer and removal, high compatibility with steam and condensation, chemical resistance, and airtightness (very low leakage). In some examples, the vacuum pump may have the ability to reduce flow to 8 tors. In some embodiments, the degassing system may omit the pump and rely on a water source flow rate (e.g., tap water flow rate) to move fluid through the system.

[0186]

[0199] Tubes / connectors / lines, made of plastic and / or metal, are configured to allow fluid and air transfer through the system and the overall acoustic / patient connection system. These also include various components such as valves (e.g., two-way, three-way, etc.).

[0187]

[0200] Electronic and manual controls provide system and user-facing control for all system functions, including but not limited to pump and degassing controls. The control system can further incorporate a range of linear and onboard sensors for detecting temperature, pressure, flow rate, dissolved oxygen concentration, volume, and more.

[0188]

[0201] The fluid system and cart can also have various electrical connections for power supply, including leveraging external power, and / or be equipped with a battery / troid to allow for a fully mobile configuration that is not connected to a power source. This allows the fluid cart to be moved to prepare / set up a histotripsy procedure and then moved away as soon as all fluid-related workflow steps are completed, so as not to require the fluid cart to be at the patient's side during the treatment / therapy.

[0189]

[0202] The fluid cart architecture and design may also include a handle, individual or central locking casters, an upper work surface, a built-in user display device, and connectivity (e.g., Ethernet), and in some embodiments, may be designed to allow for further integration of a support arm. The fluid cart architecture and design may be equipped with long / extended tubing to support in-imaging system filling / drainage, for example, when use in a CT or MRI is desired so that the overall medium / water volume is not too close to the scanner, and / or when filling during setup is required to further evaluate pre- and post-filling image / body discrepancies.

[0190]

[0203] With respect to additional details relating to the present invention, materials and manufacturing techniques may be adopted as being within the level of those skilled in the art. The same applies to method-based embodiments of the present invention in terms of additional actions that may be adopted generally or logically. It is also assumed that any optional feature of any variant of the present invention described may be described and claimed independently or in combination with any one or more of the features described herein. Similarly, references to singular items include the possibility that multiple identical items may exist. More specifically, as used herein and in the appended claims, the singular “a,” “and,” “said,” and “the” include plural referents unless otherwise explicitly stated in the context. It is further noted that the claims may be drafted to exclude any optional element. Thus, this statement is intended to function as an antecedent for the use of exclusive technical terms such as “solely,” “only,” and similar ones, along with the use of enumeration of claim elements or “negative” limitations. Unless otherwise defined herein, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art to which the invention pertains. The scope of the invention should be limited not by the specification of the subject matter, but rather by the plain meaning of the terms of the claims adopted.

Claims

1. A frame body including an upper frame body portion that defines an upper frame cavity and a lower frame body portion that defines a lower body opening, A connecting thin film partially connected to the lower frame body portion and extending across the lower body opening, comprising a connecting thin film extending across the upper frame cavity and the lower body opening, A plurality of constraint connectors intermittently arranged around the outside of the frame body, configured to releasely fix constraint members to the frame body, An ultrasonic medium container for histotripsy, equipped with [specific features / features].

2. An ultrasonic medium container according to claim 1, wherein the upper frame body portion includes an upper frame side wall extending between the upper edge and the lower edge of the side wall, and the inside of the upper frame side wall defines the upper frame cavity.

3. An ultrasonic medium container according to claim 2, wherein the circumference of the upper edge of the side wall is larger than the circumference of the lower edge of the side wall, forming an upper frame body that defines a frustoconical shape.

4. The ultrasonic medium container according to claim 2, wherein the upper frame body portion includes a support column configured to connect the ultrasonic medium container to a mechanical support arm, and the support column defines a shaped body extending outward from the outside of the upper frame body portion.

5. An ultrasonic medium container according to claim 1, wherein the plurality of constraint connectors extend upward and outward from the lower frame body portion.

6. The ultrasonic medium container according to claim 1, wherein the frame body further comprises one or more frame fasteners configured to lock the lower frame body portion to the upper frame body portion, each fastener including a fastener base fixed to the outside of the upper frame body portion, a fastener latch fixed to the outside of the lower frame body portion, a fastener handle rotatably connected to the fastener base, and a connecting rod connecting the fastener handle to the fastener latch, wherein the frame fastener is configured to move between a locked position and an unlocked position.

7. An ultrasonic medium container according to claim 6, wherein one or more frame fasteners are adjustable frame fasteners configured to adjust the gap distance between the upper frame and the lower frame.

8. An ultrasonic medium container according to claim 4, further comprising a frame support bracket configured to connect the frame body to a mechanical support arm so as to stabilize the position of the ultrasonic medium container relative to the patient.

9. An ultrasonic medium container according to claim 8, wherein the frame support bracket includes a central bracket portion and one or more support wings extending from the central bracket portion, the one or more support wings follow the outer circumference of the upper frame body, and the outer shelf portion of the upper frame body portion rests on the upper surface of one or more of the wings.

10. An ultrasonic medium container according to claim 9, wherein the central bracket portion includes two or more inner tabs extending inward from its inner surface, and the two or more inner tabs are spaced apart to define a tab cavity between them and an inner cavity shelf portion above the tab cavity.

11. An ultrasonic medium container according to claim 10, wherein the inner tab, tab cavity, and inner cavity shelf of the central bracket portion are configured to engage with the support column of the upper frame body portion.

12. An ultrasonic medium container according to claim 11, wherein the central bracket portion further comprises one or more outer tabs extending outward from its outer surface, and the one or more outer tabs are configured to engage with the mechanical support arm.

13. An ultrasonic medium container according to claim 9, wherein one or more support wings include a first support wing extending circumferentially from a first side surface of the central bracket portion around the upper frame body portion, and a second support wing extending circumferentially from a second opposite side surface of the central bracket portion around the upper frame body portion, wherein the first support wing extends between a first fixed end and a first free end and has a first central wing portion disposed between them, and the second support wing extends between a second fixed end and a second free end and has a second central wing portion disposed between them.

14. An ultrasonic medium container according to claim 13, wherein the first and second central wing portions are thinner than the first and second free ends, the first and second fixed ends, or both thereof.

15. An ultrasonic medium container according to claim 13, further comprising a gasket disposed between the upper frame body and the lower frame body to seal the frame body.

16. A frame body including an upper frame body portion that defines an upper frame cavity and a lower frame body portion that defines a lower body opening, A connecting thin film partially connected to the lower frame body portion and extending across the lower body opening, comprising a connecting thin film extending across the upper frame cavity and the lower body opening, A frame support bracket comprising an inner surface and an outer surface, wherein the inner surface is connected to the outer surface of the upper frame body portion, and the outer surface is connected to a mechanical support arm to stabilize the position of the ultrasonic medium container. An ultrasonic medium container for histotripsy, equipped with [specific features / features].

17. An ultrasonic medium container according to claim 16, wherein the frame support bracket includes a central bracket portion and one or more support wings extending from the central bracket portion, the one or more support wings follow the outer circumference of the upper frame body portion, and the outer shelf portion of the upper frame body portion rests on the upper wall of the one or more wings, the central bracket portion, or both thereof.

18. An ultrasonic medium container according to claim 17, wherein the central bracket portion includes two or more inner tabs extending inward from its inner surface, and the two or more inner tabs are spaced apart to define a tab cavity between them and an inner cavity shelf portion above the tab cavity.

19. An ultrasonic medium container according to claim 18, wherein the inner tab, tab cavity, and inner cavity shelf of the central bracket portion engage with a support column extending from the outside of the upper frame body portion.

20. An ultrasonic medium container according to claim 19, wherein the central bracket portion further comprises one or more outer tabs extending outward from its outer surface, and the one or more outer tabs engage with the mechanical support arm.

21. An ultrasonic medium container according to claim 17, wherein the one or more support wings include a first support wing extending circumferentially from a first side surface of the central bracket portion around the upper frame body portion, and a second support wing extending circumferentially from a second opposite side surface of the central bracket portion around the upper frame body portion, wherein the first support wing extends between a first fixed end and a first free end and has a first central wing portion disposed between them, and the second support wing extends between a second fixed end and a second free end and has a second central wing portion disposed between them.

22. An ultrasonic medium container according to claim 21, wherein the first and second central wing portions are thinner than the first and second free ends, the first and second fixed ends, or both thereof.

23. An ultrasonic medium container according to claim 17, further comprising a plurality of constraint connectors intermittently arranged around the outside of the frame body, wherein the constraint connectors are configured to fix constraint members to the frame body.

24. An ultrasonic medium container according to claim 23, wherein the plurality of constraint connectors extend upward and outward from the lower frame body portion.

25. A coupling assembly comprising an ultrasonic medium container, an acoustic coupling medium, and a constraint member having holes, wherein the ultrasonic medium container comprises a frame body that defines a frame cavity sealed with a coupling thin film and configured to receive the coupling medium, and a plurality of constraint connectors extending from the outside of the frame body and attaching the constraint member to the frame body through the holes, An ultrasound therapy transducer configured to provide ultrasound therapy when at least partially submerged in the acoustic coupling medium of the ultrasound medium container, A robotic positioning arm connected to the ultrasound therapy transducer, configured to move the ultrasound therapy transducer relative to the patient within the ultrasound medium container while maintaining an acoustic connection with the patient via the acoustic connection medium, and An ultrasound therapy system equipped with [specific features / equipment].

26. A coupling assembly comprising an ultrasonic medium container, an acoustic coupling medium, and a constraint member including a hole, wherein the ultrasonic medium container comprises a frame body defining a frame cavity configured to receive the coupling medium, the ultrasonic medium container being sealed with a coupling thin film, and a frame support bracket attached to the outer surface of the frame body, the frame support bracket configured to stabilize the position of the ultrasonic medium container relative to the patient when attached to a mechanical support arm, An ultrasound therapy transducer configured to provide ultrasound therapy when at least partially submerged in the acoustic coupling medium of the ultrasound medium container, A robotic positioning arm connected to the ultrasound therapy transducer, configured to move the ultrasound therapy transducer relative to the patient within the ultrasound medium container while maintaining an acoustic connection with the patient via the acoustic connection medium, and An ultrasound therapy system equipped with [specific features / equipment].

27. In a method of acoustically connecting an ultrasound therapy system to the patient's skin before treatment, A step of placing an ultrasonic medium container configured to receive an acoustic coupling medium on a patient, wherein the ultrasonic medium container includes a frame body comprising an upper frame body portion defining an upper frame cavity and a lower frame body portion defining a lower body opening, and a coupling thin film partially connected to the lower frame body portion and extending across the lower body opening, sealing the upper frame cavity, and further comprising a plurality of constraint connectors extending from the outer surface of the frame body, a frame support bracket fixed to the outer surface of the frame body, or at least one of both, For optimal acoustic coupling, the steps include locking the ultrasonic medium container in a position relative to the patient, The steps include: submerging the ultrasound therapy transducer in the ultrasound medium container and adding a sufficient amount of the acoustic coupling medium to the ultrasound medium container to bring the coupling thin film into contact with a portion of the patient's skin; The steps include introducing the ultrasound therapy device into the medium and forming an acoustic link between them. Methods that include...

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