Histotripsy System and Method

Abstract

Histotripsy therapy systems configured for the treatment of tissue are provided, which may include any number of features. Provided herein are systems and methods for providing effective, non-invasive and minimally invasive therapeutic, diagnostic, and research procedures. In particular, provided herein are systems and methods for acoustically coupling a histotripsy therapy system to a patient's epidermis to provide targeted, effective histotripsy in a variety of different regions and for a variety of different conditions without causing undesired tissue damage to intervening / non-target tissues or structures.

Description

[Technical Field]

[0001] Priority claim

[0001] This patent application claims priority to U.S. Provisional Patent Application No. 63 / 477,950, filed December 30, 2022, entitled "THERAPY TREATMENT HEAD FOR HISTOTRIPSY SYSTEMS AND METHODS," which is incorporated herein by reference in its entirety.

[0002] Incorporation by Reference

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

[0003]

[0003] This disclosure details novel high intensity therapeutic ultrasound (HITU) systems configured to produce 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, can include transducers, drive electronics, positioning robotics, imaging systems, and integrated treatment planning and control software for performing comprehensive treatment and therapy of a patient's soft tissue. [Background technology]

[0004] Histotripsy, or pulsed ultrasound cavitation therapy, is a technique in which extremely short, intense bursts of acoustic energy induce controlled cavitation (microbubble formation) within a focal volume. The violent expansion and collapse of these microbubbles mechanically homogenizes the cellular and tissue structures within the focal volume, a net result that is very different from the coagulation necrosis characteristic of thermal ablation. To operate within the non-thermal histotripsy regime, it is necessary to deliver acoustic energy in the form of low-duty-cycle, high-amplitude acoustic pulses.

[0005]

[0005] Compared with conventional focused ultrasound techniques, Histotripsy has the following important advantages: 1) the destruction process at the focal point is mechanical, not thermal; 2) cavitations appear bright on ultrasound imaging, thereby confirming correct targeting and localization of the treatment; 3) the treated tissue generally, but not always, appears darker (more hypoechoic) on ultrasound imaging, thus allowing the operator to see what has been treated; and 4) Histotripsy presents the lesion in a controlled and precise manner. It is important to emphasize that, unlike thermal ablation techniques such as microwave, radiofrequency, 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, cryo, or ionizing energy. Summary of the Invention

[0006]

[0006] An ultrasonic treatment head is provided, comprising: a therapy transducer array including an opening; and a connecting assembly disposed within the opening of the therapy transducer array, the connecting assembly being configured to receive an imaging probe and further including one or more exhaust holes configured to expel air bubbles from the distal surface of the therapy transducer array and / or the connecting assembly when the treatment head is submerged in a fluid.

[0007] In some aspects, the coupling assembly is generally cylindrically shaped.

[0008] In one aspect, the coupling assembly includes a distal portion configured to receive the imaging probe.

[0009] In some implementations, the one or more vent holes are located in the distal portion.

[0010] In one embodiment, the one or more vent holes are selected from the group consisting of two, three, and four vent holes.

[0011]

[0011] In one embodiment, the ultrasonic therapy head has at least four exhaust holes, the four exhaust holes being positioned approximately 90 degrees apart around a hole in the coupling assembly configured to receive the imaging probe.

[0012] In some aspects, one or more of the vent holes are configured to expel air bubbles from the distal surface, through the linkage assembly, and out the proximal portion of the linkage assembly.

[0013] In one aspect, the ultrasound therapy head includes one or more channels disposed along at least a portion of the longitudinal length of the linkage assembly.

[0014] In some embodiments, the one or more channels are fluidly connected to one or more vent holes in a distal portion of the connection assembly.

[0015] In one aspect, the one or more channels are configured to direct air bubbles into the cavity of the connection assembly.

[0016] In some aspects, the one or more channels are configured to direct air bubbles toward one or more vent holes in a proximal portion of the linkage assembly.

[0017] In some embodiments, the one or more channels are configured to direct air bubbles along the radiating surface of the coupling assembly toward the one or more radiating openings.

[0018] In one embodiment, the coupling assembly further includes a vent assembly disposed within the distal portion of the coupling assembly.

[0019] In some aspects, the one or more exhaust holes are formed in the exhaust assembly.

[0020] In some embodiments, the exhaust assembly includes a hole configured to receive the imaging probe.

[0021] In one aspect, the exhaust assembly includes two halves that collectively form the hole.

[0022] In some embodiments, the exhaust assembly includes a concave distal surface.

[0023] In one embodiment, the exhaust assembly is in fluid communication with the interior of the coupling assembly.

[0024] In some aspects, the connection assembly includes a cavity located proximally from the exhaust assembly.

[0025] In one aspect, the exhaust assembly is configured to direct air bubbles into the cavity through one or more exhaust holes.

[0026] In some embodiments, the coupling assembly is configured for axial translation relative to the therapy transducer array.

[0027] In one aspect, the distal surface of the linkage assembly is beveled or sloped inwardly toward the one or more vent holes.

[0028] In another aspect, the distal surface of the vent assembly is beveled or sloped inwardly toward the one or more vent holes.

[0029] In some embodiments, the connection assembly comprises a zero expansion material.

[0030] In one embodiment, the zero expansion material comprises aluminum.

[0031]

[0031] An ultrasonic treatment head is provided, comprising: a treatment head housing; a therapy transducer array connected to the treatment head housing; and a drainage channel formed between the treatment head housing and the therapy transducer array, the drainage channel being configured to facilitate removal of fluid from the treatment head when the treatment head is removed from the fluid connection container.

[0032] In one embodiment, the drainage channels are arranged radially around the periphery of the therapy transducer array.

[0033] In another aspect, the therapy transducer array is coupled to the therapy head housing with an adapter plate.

[0034] In one embodiment, the adapter plate is skeletal only.

[0035]

[0035] In some embodiments, the adapter plate is mounted on a support so as to be at least partially above the surface of the therapy transducer array to provide a gap for fluid to flow through the adapter plate toward the drainage channel.

[0036]

[0036] In one aspect, the therapy head further comprises a coupling assembly disposed within the therapy transducer array and the therapy head housing, the coupling assembly being configured for axial and rotational movement relative to the therapy transducer array and configured to include an ultrasound imaging probe.

[0037]

[0037] In some embodiments, the connection assembly further includes one or more exhaust holes configured to allow fluid to flow into the connection assembly and / or the treatment head housing when the ultrasonic treatment head is submerged in the fluid connection container.

[0038]

[0038] A coupling assembly for attaching an imaging probe to an ultrasonic treatment head is provided, comprising a cylindrical housing configured to be inserted into an opening in the ultrasonic treatment head, a hole disposed in the housing configured to receive the imaging probe, and one or more exhaust holes disposed along the hole configured to exhaust air bubbles from the distal surface of the coupling assembly.

[0039] In some embodiments, the one or more vents comprise two vents.

[0040] In another embodiment, the two exhaust holes are positioned approximately 180 degrees apart.

[0041] In one embodiment, the one or more vents comprise four vents.

[0042] In some embodiments, the four exhaust holes are positioned approximately 90 degrees apart around a hole in the coupling assembly configured to receive the imaging probe.

[0043] In one embodiment, one or more of the vent holes are configured to vent air bubbles from the distal surface, through the linkage assembly, and out the proximal portion of the linkage assembly.

[0044]

[0044] In some embodiments, the coupling assembly further includes a linear motion coupler attached to a proximal portion of the cylindrical housing, the linear motion coupler being configured to be attached to an axially translatable mechanism within the ultrasonic therapy head.

[0045] In another embodiment, the linkage assembly includes one or more channels disposed along at least a portion of the longitudinal length of the linkage assembly.

[0046] In some embodiments, the one or more channels are fluidly connected to one or more vent holes in a distal portion of the connection assembly.

[0047] In another embodiment, the one or more channels direct air bubbles into the cavity of the linkage assembly.

[0048] In some embodiments, the one or more channels direct air bubbles toward one or more vent holes in the proximal portion of the linkage assembly.

[0049] In another embodiment, the one or more channels direct air bubbles along the radiating surface of the connection assembly toward one or more radiating openings.

[0050] In one aspect, an exhaust assembly disposed within the distal portion of the coupling assembly.

[0051] In some embodiments, one or more exhaust holes are formed in the exhaust assembly.

[0052] In another embodiment, a hole is formed in the exhaust assembly and is configured to receive an imaging probe.

[0053] In one embodiment, the exhaust assembly comprises two halves that collectively form the hole.

[0054] In some aspects, the exhaust assembly is in fluid communication with the inside of the coupling assembly.

[0055] In one embodiment, the connection assembly includes a cavity located proximally from the exhaust assembly.

[0056] In some aspects, the exhaust assembly is configured to direct air bubbles into the cavity through one or more exhaust holes.

[0057] In one embodiment, the linkage assembly is configured for axial translation relative to the ultrasound treatment head.

[0058] In another aspect, the distal surface of the linkage assembly is beveled or sloped inwardly toward the one or more vent holes.

[0059] In some embodiments, the distal surface of the vent assembly is beveled or sloped inwardly toward the one or more vent holes.

[0060]

[0060] A method is provided that includes at least partially submerging a treatment head of an ultrasonic therapy system in an ultrasonic coupling container at least partially filled with a coupling medium, and directing one or more air bubbles toward an exhaust port of the treatment head to remove the air bubbles from the surface of the treatment head.

[0061]

[0061] In some embodiments, the ultrasound therapy system comprises a histotripsy therapy system.

[0062] In one aspect, the exhaust port is located in a coupling assembly that couples the imaging probe of the therapy head to the therapy transducer array of the therapy head.

[0063]

[0063] In one implementation, directing further includes moving, rotating, shoving, or vibrating the therapy head.

[0064] In one aspect, the method further includes allowing coupling medium of the ultrasound coupling container to flow into the exhaust port and the therapy head.

[0065]

[0065] In another embodiment, the method further includes removing the treatment head from the connecting medium and allowing the connecting medium to flow out of the treatment head through a drainage channel disposed in the treatment head.

[0066] In one embodiment, the surface of the therapy head comprises a therapy transducer array.

[0067]

[0067] A method is also provided that includes at least partially submerging a treatment head of an ultrasonic therapy system in an ultrasonic coupling container at least partially filled with a coupling medium, allowing the coupling medium to flow into the treatment head, at least partially removing the treatment head of the ultrasonic therapy system from the coupling medium, and allowing the coupling medium to flow out of the treatment head via a drainage channel disposed in the treatment head.

[0068] 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 of which: [Brief explanation of the drawings]

[0069] [Figure 1A]

[0069] FIG. 1 is a diagram of an ultrasound imaging and therapy system. [Figure 1B] FIG. 1 is a diagram of an ultrasound imaging and therapy system. [Figure 2A]

[0070] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2B] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2C] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2D] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2E] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2F] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2G] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2H] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2I] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2J] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2K] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2L] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2M]FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2N] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2O] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2P] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2Q] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2R] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2S] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2T] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2U] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2V] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2W] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 2X] FIG. 1 is a diagram of an embodiment of a therapy head including a therapy transducer array and an imaging probe. [Figure 3A]

[0071] 1 is a diagram of the axial movement of the ultrasound imaging probe relative to the therapy transducer and additionally the movement of the therapy transducer while the patient is in contact with the ultrasound imaging probe. [Figure 3B]1 is a diagram of the axial movement of the ultrasound imaging probe relative to the therapy transducer and additionally the movement of the therapy transducer while the patient is in contact with the ultrasound imaging probe. [Figure 3C] 1 is a diagram of the axial movement of the ultrasound imaging probe relative to the therapy transducer and additionally the movement of the therapy transducer while the patient is in contact with the ultrasound imaging probe. [Figure 3D] 1 is a diagram of the axial movement of the ultrasound imaging probe relative to the therapy transducer and additionally the movement of the therapy transducer while the patient is in contact with the ultrasound imaging probe. [Figure 4]

[0072] 10 is a flowchart illustrating a method of using a therapy head according to the present disclosure. [Figure 5A]

[0073] FIG. 10 is a diagram of a robotic arm with a quick connect assembly for attachment to a therapy head. [Figure 5B] FIG. 10 is a diagram of a robotic arm with a quick connect assembly for attachment to a therapy head. [Figure 5C]

[0074] 10A-10C are additional views of the quick connect assembly. [Figure 5D] 10A-10C are additional views of the quick connect assembly. [Figure 5E]

[0075] FIG. 1 is a diagram of an I / O cable for connecting the treatment head to a robotic system and / or ultrasound console. [Figure 5F] FIG. 1 is a diagram of an I / O cable for connecting the treatment head to a robotic system and / or ultrasound console. DETAILED DESCRIPTION OF THE INVENTION

[0070]

[0076] The disclosed systems, methods, and devices can be used for open, minimally invasive (laparoscopic and percutaneous), robotic (integrated into robotically enabled medical systems), endoscopic, or fully percutaneous extracorporeal non-invasive acoustic cavitation for the treatment of healthy, diseased, and / or injured tissue, including, but not limited to, tissue disruption, cutting, skeletonizing, and ablation. Furthermore, histotripsy can be used to create cytoskeleton formation, enabling subsequent tissue regeneration through the application of stem cells and other supportive means, due to its tissue selectivity. Finally, histotripsy can be used to trigger the release of delivered agents, such as chemotherapy and immunotherapy, by locally triggering the release of these agents through the application of acoustic energy to the target. As described below, acoustic cavitation systems can include various subsystems, including carts, therapy, integrated imaging, robotics, couplings, and software. The system may also include various other components, ancillary equipment 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 and means for creating / controlling / implementing Histotripsy are considered part of this disclosure, including any new related inventions disclosed herein.

[0071]

[0077] 1A generally illustrates a histotripsy system 100 according to the present disclosure, including a therapy transducer 102, an imaging system 104, a display and control panel 106, a robotic positioning arm 108, and a cart 110. The system may further include an ultrasound coupling interface and a source of coupling media, not shown.

[0072]

[0078] FIG. 1B is a bottom view of the therapy transducer 102 and imaging system 104. In some embodiments, the imaging system may comprise an ultrasound imaging system. As shown, the imaging system may be located at the center of the therapy transducer. Yet, other embodiments may include an imaging system located at other locations within the therapy transducer, or perhaps integrated directly into the therapy transducer. In some embodiments, the imaging system is configured to produce real-time imaging at the focal point of the therapy transducer. The system also allows multiple imaging transducers to be placed within the therapy transducer to simultaneously provide multiple views of the target tissue and combine these images into a single 3D image. Additional details regarding the therapy transducer 102 and imaging system 104, collectively referred to herein as a “therapy head” 101, are provided below.

[0073]

[0079] The histotripsy system may include one or more of a variety of subsystems, including a therapy subsystem capable of creating, applying, focusing, and delivering acoustic cavitation / histotripsy through one or more therapy transducers; an integrated imaging subsystem (or connection thereto) that allows real-time visualization of the treatment site and histotripsy effects throughout the procedure; a robotics positioning subsystem for mechanically and / or electronically steering the therapy transducer, which may further connect to / support or interact with the coupling subsystem to enable acoustic coupling between the therapy transducer and the patient; and software for communicating with, controlling, and interfacing with the system and computer-based control system (and other external systems), as well as various other components, auxiliary instruments, and accessories, including one or more user interfaces and displays and associated guided workflows, all functioning partially or together. The system may further include various fluidics and fluid management components, including, but not limited to, pumps, valves, and flow control, temperature and degassing control, and irrigation and aspiration capabilities, as well as providing and storing fluids. The system may also include various power sources and protection devices.

[0074]

[0080] As described above, the histotripsy system can include integrated imaging. Yet, in other embodiments, the histotripsy system can be configured to interface with a separate imaging system, such as a C-arm, fluoroscope, cone-beam CT, MRI, etc., to provide real-time imaging during histotripsy therapy. In some embodiments, the histotripsy system can be sized and configured to fit within a C-arm, fluoroscope, cone-beam CT, MRI, etc.

[0075] cart

[0081] The cart 110 may be configured overall in a variety of styles and form factors based on the specific intended use and procedure. In some cases, a system may include multiple carts configured in similar or different arrangements. In some embodiments, the cart may be configured and arranged for use in a radiology environment, and possibly in conjunction with imaging (e.g., CT, cone-beam CT, and / or MRI scans). In other embodiments, the cart may be arranged for use in an operating room and sterile environment for open or laparoscopic surgery and endoscopic applications, or in a robotic-enabled operating room, and may be used alone or as part of a surgical robotic procedure, with the surgical robot performing specific tasks before, during, or after use of the system and the performance of acoustic cavitation / histotripsy. Accordingly, and depending on the procedure environment based on the aforementioned embodiments, the cart may be arranged to provide sufficient workspace and access to various anatomical locations on the patient (e.g., torso, abdomen, flank, head and neck, etc.), as well as to provide workspace for other systems (e.g., anesthesia cart, laparoscopic tower, surgical robot, endoscopic tower, etc.).

[0076]

[0082] The cart may also operate with a patient surface (e.g., a table or bed) to allow the patient to be presented and repositioned in a multitude of positions, angles, and orientations, including allowing changes to such to be made pre-, peri-, and post-operatively. The cart may further be capable of interfacing and communicating with one or more external imaging or image data management and communication systems, including but not limited to one or more modalities of ultrasound, CT, fluoroscopy, cone beam CT, PET, PET / CT, MRI, optical, ultrasound, and image fusion and / or image flow; supporting a procedure and / or use environment, including physical / mechanical interoperability (e.g., compatibility within a cone beam CT workspace for collecting pre-, peri-, and / or post-histotripsy imaging data); and accessing and displaying patient medical data, including but not limited to laboratory and historical medical record data.

[0077]

[0083] In some embodiments, one or more carts may be configured to operate together. By way of example, one cart may comprise a bedside mobile cart equipped with one or more robotic arms associated with therapy transducers, therapy generators / amplifiers, etc., while a companion cart operating with and away from the patient may comprise integrated imaging and console / display for controlling the robot and therapy facets similar to a surgical robot and master / slave configuration.

[0078]

[0084] In some embodiments, the system may include multiple carts, all slave to one master cart, equipped to perform acoustic cavitation procedures. In some arrangements and in some cases, one cart configuration may allow for storage of specific subsystems at a distance that reduces clutter in the operating room, while another cooperating cart may essentially include bedside subsystems and components (e.g., delivery systems and therapies).

[0079]

[0085] Numerous permutations and configurations of cart designs are possible, and these examples are not intended to limit the scope of this disclosure in any way.

[0080] Histotripsy

[0086] Histotripsy uses short, high-amplitude focused ultrasound pulses to generate a dense, energetic "bubble cloud" capable of targeted disruption and destruction of tissue. Histotripsy has the ability to create controlled tissue erosion when directed at tissue interfaces, including tissue / fluid interfaces, as well as well-defined tissue disruption and destruction at the subcellular level when targeted at bulk tissue. Unlike other forms of ablation, including thermal and radiation-based modalities, Histotripsy does not rely on heat, cold, or ionizing energy to treat tissue. Instead, Histotripsy uses acoustic cavitation generated at a focal point to mechanically affect tissue structure, potentially liquefying, suspending, dissolving, and / or disrupting tissue into subcellular components.

[0081]

[0087] Histotripsy can be applied in various forms, including: 1) Intrinsic Threshold Histotripsy: A pulse is delivered with one to two cycles of high-amplitude reverse / extensional pressure that exceeds the intrinsic threshold for generating cavitation in the medium (e.g., approximately 24-28 MPa for aqueous soft tissue). 2) Shock-Scattering Histotripsy: A pulse of three to 20 cycles is typically delivered within a duration. Scattered shock waves (compression / forward phase) from the initial individual microbubbles generate a counter shock wave that constructively interferes with the incoming reverse / extensional phase to form a high-amplitude reverse / extensional phase that exceeds the intrinsic threshold. In this way, a cluster of cavitation microbubbles is generated. The amplitude of the extensional 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 scatter the incident shock wave, reversing it and constructively interfering with it to exceed the threshold for intrinsic nucleation. and 3) boiling histotripsy: employing pulses of approximately 1-20 ms in duration. Absorption of the impinging pulse rapidly heats the medium, thereby reducing the intrinsic nucleus threshold. When this intrinsic threshold coincides with the peak negative pressure of the incident wave, a boiling bubble forms at the focus.

[0082]

[0088] The large pressures generated at the focal point generate a cloud of acoustic cavitation bubbles above 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 focal point. This cavitation effect is only observed at pressure levels significantly greater than those that define the inertial cavitation threshold in water for similar pulse durations, around 10 to 30 MPa peak negative pressure.

[0083]

[0089] Histotripsy can be performed in numerous ways and under different parameters. Histotripsy can be performed completely noninvasively 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 overlying (and intervening) tissue. Histotripsy application is not limited to percutaneous approaches, but can be applied through any means that allows transducer contact with tissue, including open, laparoscopic, percutaneous, and robotic surgical procedures. This allows for further targeting, planning, directing, and observation under direct visualization via ultrasound imaging, given that the bubble cloud generated by Histotripsy can be visible, for example, as a highly dynamic echogenic region on B-mode ultrasound images, allowing continuous visualization throughout its use (and associated procedures). Similarly, treated and disrupted tissue exhibits dynamic changes (typically reductions) in echogenicity that can be used to assess, plan, observe, and monitor treatment.

[0084]

[0090] Generally, in histotripsy treatment, an ultrasound pulse with one or more acoustic cycles is applied, and bubble cloud generation relies on the pressure-relief scattering of a positive shock front (sometimes exceeding 100 MPa, P) from an initially initiated, slightly dispersed bubble (or single bubble). This is referred to as the "shock scattering mechanism."

[0085]

[0091] This mechanism relies on a single (or a few sparsely dispersed) bubble being initiated during the initial negative half-cycle of the pulse at the transducer focal point. A microbubble cloud is then generated by the pressure-relief backscattering of a high-peak positive shock front from these sparsely initiated bubbles. These backscattered high-amplitude rarefaction waves exceed the intrinsic threshold, thus creating a localized high-density bubble cloud. Each subsequent acoustic cycle then induces further cavitation by backscattering from the bubble cloud's surface, which grows toward the transducer. As a result, an elongated high-density bubble cloud growing along the acoustic axis opposite to the ultrasound propagation direction is observed in the impact scattering mechanism. This impact scattering process makes bubble cloud generation dependent not only on the peak negative pressure but also on the number of acoustic cycles and the amplitude of the positive shock. Without at least one strong shock front caused by nonlinear propagation, a high-density bubble cloud is not generated when the peak negative half-cycle falls below the intrinsic threshold.

[0086]

[0092] When ultrasound pulses of less than two periods are applied, impact scattering can be minimized, and the generation of a dense bubble cloud depends on the negative half-period of the applied ultrasound pulse exceeding the "intrinsic threshold" of the medium. This is called the "intrinsic threshold mechanism."

[0087]

[0093] This threshold can be in the range of 26-30 MPa for soft tissues with a high water content, such as human tissue. In some embodiments, using this intrinsic threshold mechanism can result in well-defined and more predictable spatial extent of the lesion. With peak negative pressures (P-) not significantly higher than this threshold, subwavelength reproducible lesions as small as half the transducer's -6 dB beamwidth can be generated.

[0088]

[0094] With high-frequency histotripsy pulses, the minimum reproducible lesion size is smaller, which is beneficial for applications requiring precise lesion creation. However, high-frequency pulses are more susceptible to attenuation and aberrations, making treatment at greater penetration depths (e.g., ablation deep within the body) or through highly aberration-prone media (e.g., transcranial procedures, or procedures in which the pulse is transmitted through bone) uncertain. Histotripsy also applies because low-frequency "pump" pulses (typically <2 cycles and having frequencies between 100 kHz and 1 MHz) can be applied together with high-frequency "probe" pulses (typically <2 cycles and having frequencies greater than 2 MHz or ranging between 2 MHz and 10 MHz), and the peak negative pressures of the low and high-frequency pulses can structurally interfere to exceed the intrinsic threshold of the target tissue or media. Low-frequency pulses, which are more tolerant of attenuation and aberrations, can raise peak negative pressure P- levels in a region of interest (ROI), while high-frequency pulses, which offer greater precision, can pinpoint target locations within the ROI and raise peak negative pressure P- above intrinsic thresholds. This approach is sometimes referred to as "dual frequency," "dual beam histotripsy," or "parametric histotripsy."

[0089]

[0095] Additional systems, methods, and parameters for implementing optimized Histotripsy using impact scattering, intrinsic thresholds, and various parameters enabling frequency compounding and bubble manipulation are included herein as part of the systems and methods disclosed herein, including additional means for controlling such Histotripsy effects as related to steering and positioning the focal spot and simultaneously managing tissue effects (e.g., focal thermal collateral damage) at the treatment site or within intervening tissue. Furthermore, various systems and methods are disclosed as being included as part of the present disclosure, including future contemplated embodiments of such, which may include multiple parameters such as, but not limited to, frequency, operating frequency, center frequency, pulse repetition frequency, pulses, bursts, number of pulses, period, pulse length, pulse amplitude, pulse duration, delay, burst repetition frequency, sets of the former, multiple sets of loops, multiple and / or different sets of loops, sets of loops, and various combinations or permutations thereof.

[0090] Therapy Components

[0096] The therapy subsystem can operate with other subsystems to create, optimize, deliver, visualize, monitor, and control acoustic cavitation, also referred to herein and hereinafter as "histotripsy" and its derivatives, including boiling histotripsy and other thermal high frequency ultrasound approaches. It is noted that the disclosed invention may also benefit from other acoustic therapies that do not include cavitation, mechanical, or histotripsy components. The therapy subsystem can include, among other features, an ultrasound therapy transducer and pulse generator system configured to deliver ultrasound pulses to tissue.

[0091]

[0097] To produce and deliver histotripsy and histotripsy derivatives, the therapy subsystem may also include components including, but not limited to, one or more function generators, amplifiers, therapy transducers, and power sources.

[0092]

[0098] Therapy transducers can comprise single or multiple elements configured to be excited with high-amplitude electrical pulses (>1000V, or any other voltage that may cause harm to the body). The amplitude required to drive a therapy transducer for histotripsy varies depending on the transducer design and material used (e.g., solid or polymer / piezoelectric composites, including ceramic or single crystal), and the transducer center frequency, which is directly proportional to the thickness of the piezoelectric material. Thus, transducers operating at high frequencies require lower voltages to generate a given surface pressure than those required by low-frequency therapy transducers. 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 composition. In some embodiments, the transducer elements can be formed using silicon using MEMs technology, including CMUT and PMUT designs.

[0093]

[0099] In some embodiments, the function generator may include a field programmable gate array (FPGA) or other suitable function generator. The FPGA may be configured with parameters previously disclosed herein, including but not limited to frequency, pulse repetition frequency, burst, number of bursts, where a burst may include a pulse, number of pulses, pulse length, pulse duration, delay, burst repetition frequency or duration, a set of bursts may include a set of parameters, a set of loops may include various sets of parameters with or without a delay or various delays, multiple loop sets of various time delays and independently controlled, and various combinations and permutations of such, throughout, may be repeated, and / or new loop sets may be introduced.

[0094]

[0100] In some embodiments, the generator or amplifier may be a general-purpose single-cycle or multi-cycle pulse generator configured to support drive via Class D or inductive drive and across all envisioned clinical applications and use environments, some of which are further discussed later in this disclosure. In other embodiments, the Class D or inductive current driver may be configured with converter and / or automatic converter drive circuitry to further provide step-up / down components and, in some cases, preferably to enable amplitude step-up. These may also include inherent protection features to further support the system and provide the ability to protect other components of the system (e.g., therapy transducer and / or amplifier circuitry) and / or the user from various threats, including, but not limited to, the use environment, electrical safety threats that could potentially lead to the system and therapy system, and user harm, adverse effects, or problems.

[0095]

[0101] The disclosed generators can enable and support the system's ability to select, vary, and control (through available software tools) various parameters, 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 cycles, active channels and delays, etc., modulate pulse amplitude on fast time scales independent of the high voltage source, and / or perform other service, diagnostic, or therapeutic features.

[0096]

[0102] In some embodiments, the therapy subsystem and / or its components, such as amplifiers, may further comprise integrated computer processing capabilities, may be networked, connected, accessed, and / or may be removable / portable, modular, and / or interchangeable between systems, and / or may be driven / commanded from / by other systems, or various combinations. Other systems may include other acoustic cavitation / histotripsy, HIFU, HITU, radiation therapy, radiofrequency, microwave, and cryoablation systems, navigation and localization systems, open surgery, laparoscopic, single incision / single port, endoscopic, and non-invasive surgical robotics, laparoscopic or surgical towers with other energy-based or vision systems, surgical system racks or booms, imaging carts, etc.

[0097]

[0103] In some embodiments, the amplifier or amplifiers may comprise a class-D amplifier and associated drive circuitry, including matching network components. Depending on the electrical impedance of the transducer element and the selection of matching network components (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 produce 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, matching network components or inductors, and transformer or autotransformer, and may typically be in the low kV (e.g., 1-3 kV) range.

[0098]

[0104] The therapy transducer elements are excited with an electrical waveform having an amplitude (voltage) sufficient to produce a pressure output sufficient for histotripsy therapy. The excitation field can be defined as the required waveform voltage per thickness of the piezoelectric element. For example, a piezoelectric element operating a transducer at 1 MHz will be half the thickness of an equivalent 500 kHz element, and will therefore require half the voltage to achieve the same electric field and surface pressure.

[0099]

[0105] The therapy subsystem can also include therapy transducers of various designs and working parameters to support use in various treatments (and treatment environments). The system may be configured with one or more therapy transducers that are further interchangeable and can operate with various aspects of the system in similar or different ways (e.g., can interface to a robotic arm using common interfaces and interchange features, or conversely, can be adapted to operate with application-specific imaging probes, where different imaging probes can interface and integrate with therapy transducers in specifically different ways).

[0100]

[0106] Therapy transducers may be constructed from a variety of parameters that may include size, shape (e.g., rectangular or circular, anatomically curved housing, etc.), geometry, focal length, number of elements, size of elements, distribution of elements (e.g., number of rings in an annular pattern transducer, size of rings), frequency, enabling electronic beam steering, etc. Transducers may be constructed from a variety of materials (e.g., piezoelectric, silicon, etc.), form factors and types (e.g., machined elements, chip-based, etc.), and / or by a variety of methods of fabrication.

[0101]

[0107] Transducers can be designed and optimized for clinical applications (e.g., abdominal tumors, peripheral vascular disease, fat ablation, etc.) and desired outcomes (e.g., acoustic cavitation / histotripsy without thermal injury to intervening tissues), as well as to provide a wide range of working conditions, including relatively shallow, superficial targets (e.g., thyroid or breast nodules) and deeper or more difficult-to-reach targets such as centrally located liver or brain tumors. They can be configured to enable acoustic cavitation / histotripsy under various parameters and sets, as enabled by the system components described above (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 period, synchronization pulse, synchronization pulse delay, various loop sets, etc., and permutations thereof. Transducers can also be designed to enable activation of drug payloads stored in tissues through various means, including injection, displacement, or delivery in micelles or nanostructures.

[0102] Integrated Imaging

[0108] The disclosed system can include various imaging modalities that allow the user to visualize, monitor, and collect / use feedback of the patient's anatomy, related areas of interest and treatment / treatment site, as well as surrounding and intervening tissues, to assess, plan, and perform treatment and adjust treatment parameters as needed. Imaging modalities can include various ultrasound, X-ray, CT, MRI, PET, fluoroscopic, optical, contrast- or agent-enhanced versions, and / or various combinations thereof. It is further disclosed that various image processing and characterization techniques can also be utilized to provide enhanced visualization and user decision-making. These can be selected or commanded manually by the user or automatically by the system. The system can be configured to enable side-by-side imaging, toggling, overlay, 3D reconstruction, segmentation, registration, multimodal image fusion, image flow, and / or any other method that allows the user to identify, define, and communicate various aspects of using imaging during treatment as displayed in various system user interfaces and displays. Examples may include, by way of non-limiting example, identifying important structures such as vessels, ducts, nerves, ureters, fissures, capsules, tumors, tissue trauma / injury / disease, other organs, connective tissues, and / or one or more important structures in context with each other (e.g., tumor-draining lymphatics or vasculature, or tumors close to organ capsules or other underlying organs) to locate, display, and characterize potential treatment sites within, on, and / or surrounding an area, organ system, organ, or tissue of interest.

[0103]

[0109] The system may be configured to include on-board integrated imaging hardware, software, sensors, probes, and software, and / or may be configured to communicate and interface with external imaging and image processing systems. The aforementioned components may also be integrated into the system's therapy subsystem components, including probes, imaging arrays, or the like, and electrically, mechanically, or electromechanically integrated with the therapy transducer. This may, in part, provide the ability to perform geometrically aligned imaging and therapy, with therapy directly within the field of view and possibly in line with the imaging. In some embodiments, this integration may provide a fixed orientation of the imaging capability (e.g., imaging probe) to the therapy transducer in a contextualized manner. In other embodiments, the imaging solution may have the ability to move or adjust its position, including modifying angle, range (e.g., distance from the therapy transducer or patient), rotation (e.g., imaging plane in the example of an ultrasound probe), and / or other parameters, including dynamically moving / adjusting them while actively imaging. The imaging component or probe may be encoded such that its orientation and position relative to another aspect of the system, such as a therapy transducer and / or a robotic-enabled positioning component, may be determined.

[0104]

[0110] In one embodiment, the system can include an on-board ultrasound further configured to allow the user to visualize, monitor, and receive feedback about the treatment site through the system display and software, including enabling ultrasound imaging and characterization (and its various forms), ultrasound-guided planning, and ultrasound-guided therapy, all in real time. The system can be configured to allow the user to image the patient manually (e.g., by hand or using a robotic-enabled imager), semi-automated, or fully automated means.

[0105]

[0111] In some embodiments, imaging feedback and monitoring can include monitoring changes in backscatter from the bubble cloud, backscatter speckle reduction, backscatter speckle statistics, tissue mechanical properties (i.e., elastography), tissue perfusion (i.e., ultrasound contrast), shear wave propagation, acoustic emission, electrical impedance tomography, and / or various combinations thereof, including those displayed in or integrated with other forms of imaging (e.g., CT or MRI).

[0106]

[0112] In some embodiments, imaging including feedback and monitoring from backscatter from the bubble cloud can be used as a method for quickly determining whether the histotripsy process has been initiated, properly maintained, or possibly extinguished. For example, this method allows drug delivery, tissue erosion, and the like to be continuously monitored in real time. The method can also provide feedback that allows the histotripsy process to be initiated at high intensity and maintained at much lower intensity. For example, backscatter feedback can be monitored by any transducer or ultrasound imager. By measuring the feedback of the therapy transducer, an accessory transducer can be configured to deliver interrogation pulses or passively detect cavitation. Furthermore, the nature of the received feedback can be used to adjust acoustic parameters (and associated system parameters) to optimize drug delivery and / or the tissue erosion process.

[0107]

[0113] In some embodiments, imaging including feedback and monitoring from backscatter and speckle reduction may be configured in the system.

[0108]

[0114] In systems with feedback and monitoring via backscatter, as well as by way of background, as tissue is gradually mechanically subdivided—in other words, homogenized, nonviable, or eroded—this process results in changes in the size and distribution of acoustic scatterers. At some point in the process, the scattering particle size and density are reduced to a level where ultrasound is barely scattered, or the amount scattered is significantly reduced. This results in a significant reduction in speckle, which is the coherent constructive and destructive interference pattern of bright and dark spots seen in images when a coherent illumination source, in this case ultrasound, is used. After some treatment time, speckle reduction results in dark areas within the treatment volume. The amount of speckle reduction is related to the amount of tissue subdivision and can therefore be related to the size of the remaining tissue fragments. When this size is reduced to a subcellular level, it is not expected that cells will survive. Thus, treatment can proceed until the desired speckle reduction level is reached. Speckle is easily seen and evaluated on standard ultrasound imaging systems. Specialized transducers and systems, including those disclosed herein, can also be used to evaluate backscatter changes.

[0109]

[0115] Furthermore, in systems with feedback and monitoring via speckle, as well as by means of background, the image persists from frame to frame and remains largely unchanged unless the scattering distribution changes and the imaged object moves. Nevertheless, scattering may change enough to be detected by signal processing and other means long before it is reduced to a size sufficient to cause speckle reduction. This collection of techniques can act as a detector of speckle statistical changes. For example, the size and location of one or more speckles in the image begin to decorrelate before observable speckle reduction occurs. Speckle decorrelation, after appropriate motion compensation, can be a sensitive measure of tissue mechanical inviability and therefore a measure of therapy efficacy. This feedback and monitoring technique can enable early observation of changes resulting from the acoustic cavitation / histotripsy process and can identify tissue changes (e.g., the onset of erosion) before substantial or complete tissue effects occur. In one embodiment, this method can be used to monitor acoustic cavitation / histotripsy processes for enhanced drug delivery when the treatment site / tissue is temporarily rendered non-viable and tissue damage / erosion is not desired. In other embodiments, this can involve speckle decorrelation with scattering shift in an increasingly fluidized therapy volume, for example, when partial or complete tissue erosion is desired.

[0110]

[0116] For systems with feedback and monitoring via elastography, as well as background measures, as the treatment site / tissue is further subdivided (homogenized, rendered nonviable, or eroded) per acoustic cavitation / histotripsy effect, its mechanical properties change from a soft but interconnected solid to a mucus or paste with few long-range interactions. These changes in mechanical properties can be measured by various imaging modalities, including MRI and ultrasound imaging systems. For example, ultrasound pulses can be used to generate forces (i.e., radiation forces) on localized volumes of tissue. Tissue response (displacement, tension, and velocity) can be significantly altered during histotripsy treatment, allowing the state of tissue nonviability to be determined by imaging or other quantitative means.

[0111]

[0117] The system can also provide feedback and monitoring via shear wave propagation changes. As a background measure, tissue repartitioning makes the tissue more fluid and less solid, and fluid systems generally do not propagate shear waves. Therefore, 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 treated volume is used as a measure of tissue destruction or non-viability. 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 can affect tissue by pushing it in a specific 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 must be detected externally, for example, by a difference frequency that is detected only when two shear waves interact nonlinearly, and the disappearance of the waves can be correlated to tissue damage. Therefore, the system may be configured to use this modality to enhance feedback and monitoring of acoustic cavitation / histotripsy procedures.

[0112]

[0118] For systems with feedback and monitoring via acoustic emissions, as well as background measures, when a tissue volume is subdivided, its effect on acoustic cavitation / histotripsy (e.g., here, bubble clouds) is altered. For example, bubbles may grow larger and have different lifetimes, disrupting the varying properties of intact versus fluidized tissue. Bubbles may also move and interact after tissue is subdivided, creating larger bubbles or cooperative interactions between bubbles, all of which can produce changes in acoustic emissions. These emissions can be heard and change during treatment. Analysis of these changes and their correlation with therapy efficacy allows for monitoring of therapy progress and can be configured as a system feature.

[0113]

[0119] In systems with feedback and monitoring via electrical impedance tomography, and as a background measure, an impedance map of the therapy site can be generated based on the spatial electrical characteristics throughout the therapy site. Imaging of the patient's therapy site's conductivity or permittivity can be inferred from skin surface electrical measurements. Conductive electrodes are affixed 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 voltage is measured at several points using the electrodes. The process can be repeated for different configurations of applied current. The resolution of the resulting image can be adjusted by varying the number of electrodes employed. Measures of the therapy site's electrical properties within the skin surface can be obtained from the impedance map, and changes and locations of acoustic cavitation / histotripsy (e.g., specifically bubble clouds), as well as histotripsy processes, can be monitored using this as configured in the system and supporting subsystems.

[0114]

[0120] Through the system software and user interface and display, the user may be enabled to further select, annotate, mark, highlight, and / or outline various regions of interest or treatment sites, as well as predefined treatment targets (on the image) that can be used to command and direct the system where to image, test, and / or treat. In some arrangements, the user may perform the procedure using a manual ultrasound probe (e.g., a diagnostic handheld probe). In other arrangements, the system may use a robotic and / or electro-mechanical positioning system to perform the procedure in a system-directed and / or automated manner, or conversely, the system may allow for a combination of manual and automated usage.

[0115]

[0121] The system may further include the capability to perform image registration, including imaging and image dataset registration, to enable navigation and localization of the system to the patient, including the treatment site (e.g., tumor, critical structures, bony anatomy, anatomical structures and their identifying features, etc.). In one embodiment, the system allows a user to image and identify an area of ​​interest, such as the liver, using integrated ultrasound and select and mark a tumor (or a surrogate marker) contained within the liver through / displayed in the system software, the system registering the image data to a coordinate system defined by the system, further enabling the therapy and robotics subsystem of the system to deliver synchronized acoustic cavitation / histotripsy to the marked tumor. The system may be capable of registering various image sets, including those previously disclosed, with each other and providing navigation and localization (e.g., of a therapy transducer to a CT or MRI / ultrasound fusion image with the therapy transducer and robotics subsystem tracking to the image).

[0116]

[0122] The system may also be capable of operating in a variety of interventional endoscopic and surgical environments, including alone and with 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.) that may operate with or include various optical imaging capabilities (e.g., fiber and / or digital). The disclosed system may be configured to operate with these systems, and in some embodiments, operate in conjunction with them, or in other embodiments, all or part of the system may be integrated into the above systems / platforms (e.g., acoustic cavitation / histotripsy-enabled endoscopic systems or laparoscopic surgical robots). In many of these environments, the therapy transducers may be used, for example, at or around the time of use of an optically guided endoscope / bronchoscope, or as another example, a laparoscopic robot (e.g., Intuitive Digital Vinci*Xi system) is viewing / manipulating the tissue / treatment site. Additionally, these embodiments and examples can include cases where the other systems / platforms described above are used to deliver fluid (locally) to enable the creation of artificial acoustic windows that may not exist under normal circumstances (e.g., fluidizing a lung segment or lobe in preparation for acoustic cavitation / histotripsy via non-invasive transthoracic treatment (e.g., with transducers placed externally on / around the patient)). The systems disclosed herein can also include all or part of these subsystem hardware packaged within other system carts / consoles / systems described herein (e.g., acoustic cavitation / histotripsy systems and / or subsystems integrated and operated from the navigation or laparoscopic systems described above).

[0117]

[0123] The system may also be configured through various of the aforementioned and other parameters to spatiotemporally display real-time visualization of the bubble cloud, including resulting tissue effects during / after 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 continuously track and follow the treatment in real time with one integrated procedure and interface / system, and to confirm treatment safety and efficacy during operation (versus other interventional or surgical modalities that require multiple procedures to accomplish the same, or where the treatment effect is not visible in real time (e.g., radiation therapy) or where such (e.g., real-time visualization of localized tissue during thermal ablation) is not achievable, and / or where other procedures further require invasive approaches (e.g., incisions or drilling) and repeated imaging in a scanner (e.g., CT or MRI scans) between treatment steps). The above disclosed systems, subsystems, components, modalities, features, and workflows / methods of use may be implemented without limitation through enabling hardware, software, user interfaces, and environments of use, and any resulting data and means of using said data for analytics, artificial intelligence, or digital health applications and systems, as well as future improvements, enhancements, and inventions in this area, are considered within the scope of this disclosure.

[0118] Treatment head

[0124] The present disclosure provides a treatment head design that typically includes a histotripsy therapy transducer, an integrated coaxial ultrasound imaging probe, probe rotation and translation features including position encoders, and mechanical, electrical, and software support and / or associated interfaces for controlling various treatment head features and functions, including various user interaction points and interfaces, from installation, setup, and through clinical treatment workflow, and treatment simulation and pre-planning support.

[0119]

[0125] FIG. 2A provides additional details about a therapy head 201 of a histotripsy system, which may include a histotripsy or therapy transducer array 202 and an imaging probe 204. The imaging probe 204 can be configured to translate axially and rotate within a bore in the therapy head. The therapy head can include a housing 206 that can cover and / or protect the internal components of the therapy head. For example, FIG. 2A shows the therapy head with the housing intact, while FIG. 2B shows the therapy head with the housing removed, providing an overview of the internal components.

[0120]

[0126] 2A , the therapy head 201 can include one or more handles 208 to enable physical manipulation of the therapy head. While the illustrated embodiment shows a pair of handles 208 facing another handle on the therapy head, it should be understood that fewer or more than two handles may be incorporated. In some embodiments, one or more handles 208 can include a user input device 210. The user input device can include, for example, a button, a lever, a switch, a graphical user interface (GUI), or the like. The button can be, for example, a physical button or an electronic / capacitive button. In some implementations, the user input device 210 can enable or control functionality of the therapy head or a robotic system to which the therapy head is mounted. For example, in one embodiment, when depressed or initiated, the user input device 210 can change the system state from robot-driven control, in which the robotic system is entirely responsible for positioning and moving the therapy head, to free-drive control, in which the user can move or manipulate the position and / or orientation of the therapy head. Generally, free-drive control can be configured so that the robotic system supports or holds the weight of the therapy head in the appropriate position in 3D space, but additional force applied to the therapy head by the user can allow movement or rotation of the therapy head. In some implementations, there can be various degrees or levels of free-drive control. For example, a first level of free-drive control can only allow the user to manipulate the therapy head in a single plane (e.g., axially along the z-plane, or alternating left and right along either the x- or y-plane). Other levels of free-drive control can allow rotation of the therapy head about an axis (e.g., the z-axis), movement in two or more planes or axes, etc. In some embodiments, various degrees or levels of free-drive control can be cycled through or selected with the user input device 210.

[0121]

[0127] The handle may be further configured to enable / support a user to efficiently attach and release the therapy head to / from the robotic arm (including rapid exchange of application-specific therapy heads), and the handle interfaces between the top surface of the therapy transducer (or interface to the therapy transducer) and the central leg of the therapy head (comprising the electrical / mechanical internal components and imaging probe).

[0122]

[0128] In some embodiments, the handle design, profile, and geometry may also be designed to preferentially interact with the coupling system (and defined workspace geometry / volume) to allow for desired placement (depth, angle, trajectory, etc.) within the coupling system to minimize / avoid collisions, etc. In other embodiments, the handle may be monolithic with the treatment head.

[0123]

[0129] In certain embodiments, the handles are configured to facilitate manipulation of the therapy head. The handles may be symmetrical or mirror images of one another. As illustrated at least in FIGS. 2A and 2K, the handles may be symmetrical and concave in shape. The handles may have a curvature of approximately 24 degrees along the inner portion 208a of the handle (see also FIG. 2P). The corresponding outer portion 208b may also be disposed at a curvature of approximately 24 degrees. In some embodiments, the curvature of the inner and outer portions of the handles may range from 20 to 30 degrees, or alternatively, from 15 to 35 degrees. One or more of the handles may be hollow or carved to allow cables, wires, tape, or other electrical and non-electrical components to be threaded through. In particular, a rotary encoder cable runs through the inside of at least one of the handles and connects to the PCB. Hollowed handles also reduce the overall therapy head weight. To achieve the desired durability and support while maintaining the complex shape and hollowed out design, a direct metal laser sintering process can be used to fabricate the handle components from aluminum.

[0124]

[0130] Additional buttons, dials, knobs, or user input devices can be included on the treatment head. For example, the embodiment of FIG. 2A further includes an imaging probe control 212. The imaging probe control 212 can be configured to control the axial movement of the imaging probe 204. In this embodiment, the imaging probe control 212 is implemented as a knob or dial. The dial or knob imaging probe control 212 can control the axial movement of the imaging probe electronically via a motor or mechanically, as described below.

[0125]

[0131] In one embodiment, the imaging probe control 212 provides direct mechanical control of the axial movement of the imaging probe relative to the therapy transducer array. For example, the rotation of the imaging probe control 212 can control a direct mechanical linkage of the imaging probe that enables axial manipulation. Alternatively, the rotation of the imaging probe can be controlled directly with a rotating sleeve 221, which can be directly coupled to the imaging probe (e.g., with a groove and key or other mechanical mechanism). Additional details about the axial and rotational mechanical control of the imaging probe are described below with respect to the embodiment of FIG. 2E.

[0126]

[0132] In some embodiments, the imaging probe control 212 can control both axial movement and rotation of the imaging probe relative to the therapy transducer. For example, embodiments can achieve electronic control of the imaging probe via the imaging probe control 212 using one or more motors electrically coupled to the imaging probe control 212 and physically connected or coupled to the imaging probe. In one embodiment, one motor can be responsible for axial movement and a second motor for rotation, both controlled by the imaging probe control 212 (or multiple imaging probe controls).

[0127]

[0133] When the imaging probe control 212 is set to control rotation, rotation of the knob or dial can result in a corresponding rotation of the imaging probe. For example, rotation of the imaging probe control 212 in a clockwise direction can result in a corresponding rotation of the imaging probe in the same clockwise direction (as viewed from the bottom of the therapy head). Alternatively, clockwise rotation of the imaging probe control can result in counterclockwise rotation of the imaging probe. Any combination of rotation or manipulation of the imaging probe control and rotation of the imaging probe is envisioned. Additionally, the amount of rotation imparted to the imaging probe relative to the amount of rotation of the imaging probe control 212 can be customized. For example, in some embodiments, there is a 1:1 ratio of rotation of the imaging probe control 212 to the actual rotation of the imaging probe (i.e., turning the imaging probe control by 90 degrees results in a corresponding 90-degree rotation of the imaging probe). In other embodiments, the ratio may be 1:2, 1:3, 1:4, 2:1, 3:1, 4:1, etc. In some embodiments, the ratio can be user-selectable according to user settings.

[0128]

[0134] In some embodiments, switching between rotational and axial movement modes can be achieved by interrupting the imaging probe control 212. Alternatively, a separate button or input device can be used to switch between modes. Additionally, in some embodiments, a separate imaging probe control 212 can be provided to allow independent and simultaneous control of both rotational and axial movement. In other embodiments, an input device may be provided (e.g., a joystick or similar input device) that allows rotational and axial control without the need to switch modes.

[0129]

[0135] When the imaging probe control is set to control axial movement, rotation of the imaging probe control can result in axial translation of the imaging probe relative to the therapy transducer. For example, clockwise rotation of the imaging probe control can advance the imaging probe along the z-axis (e.g., extend it distally away from the therapy transducer), and counterclockwise rotation can retract the imaging probe along the z-axis (e.g., extend it proximally toward the therapy transducer), and vice versa.

[0130]

[0136] 2A and 2C further illustrate a robotic arm coupler 214 configured to provide a secure connection of the histotripsy system to a robotic arm. FIG. 2C provides a close-up view of the robotic arm coupler 214. In FIG. 2C, the robotic arm coupler can include attachment features 215 that can be configured to securely engage with corresponding attachment features on the robotic arm. In some embodiments, the attachment features on the robotic arm coupler can provide a secure attachment to the robotic arm by rotating the therapy head and locking everything in place. A claw on the coupler 214 can interact with an engaging or extending feature on the robotic arm. A button 217 can be depressed to release or disconnect the coupler 214 from the robotic arm.

[0131]

[0137] 2A and 2C show separate electrical connection wires or I / O cables 216 that can provide electrical connections between all of the electronics in the treatment head and the console or cart of the histotripsy system (e.g., via a robotic arm connection). These electrical connections can include, for example, electrical connections to the therapy transducer array, imaging probe, motors controlling the rotational / axial movement of the imaging probe, linear and rotary encoders, any of the user input devices, and additionally any other sensors or electronics located on or in the treatment head. While separate electrical connections are shown, it should be understood that in other embodiments, the electrical connections can be made directly through the robotic arm coupler without requiring separate connecting wires. This implementation can include, for example, electrical contacts configured to mate with corresponding electrical contacts on the robotic arm.

[0132]

[0138] A quick release connector or robot arm coupler (described later) is configured to enable rapid exchange of the treatment head (and its design), which may include providing electrical / mechanical support (e.g., connecting an encoder to the system / system software via the robot arm I / O at the distal end of the arm / adjacent tool flange).

[0133]

[0139] Additionally, the general interface design described herein includes a general mechanical design approach for interfacing a therapy transducer array to a central leg / handle / housing to allow for wide flexibility in therapy transducer design while maintaining a similar therapy head design and interface to the robotic arm. Additionally, the robotic arm and control system, and software as implemented / integrated, may also be designed to include specific monitoring and watchdog for various force / torque sensors, force fault systems and methods for triggering various categories of failures (of various risk / concern levels), and the ability to alert, notify, interact with, and recover from one or more types of force faults.

[0134]

[0140] 2A additionally shows an exhaust or drainage channel 218, which can be configured to provide one or both of the following: 1) exhaust air from the concave surface of the therapy transducer array when the therapy head is placed in the acoustic coupling medium (e.g., prior to therapy); and 2) allow the coupling medium to flow out of the therapy head after the therapy head is removed from the acoustic coupling medium. The drainage channel 218 can be a circumferential drainage channel that extends around the entire periphery of the therapy head and / or therapy transducer array. In other embodiments, the drainage channel extends only partially around the periphery of the therapy head and / or therapy transducer array. Additional details regarding the exhaust and drainage of the therapy head are provided below.

[0135]

[0141] Referring again to FIG. 2A , the therapy head may further include a window 220 configured to provide an overview of the coupling assembly. In some embodiments, the window 220 may allow a user to visualize the axial position of the imaging probe and coupling assembly relative to the therapy transducer array, such as with markings or measurements (not shown) placed on the coupling assembly. In another embodiment, one or more tabs or other protruding features 222 may extend out from the coupling assembly to provide a physical stop for the axial translation of the imaging probe. For example, the protruding features 222 may abut or contact the proximal and / or distal ends of the window 220 to maintain the axial translation of the imaging probe within defined limits. The window 220 may also provide a path for any additional cables or connections to exit the therapy head, such as an ultrasound imaging cable (not shown).

[0136]

[0142] As mentioned above, FIG. 2B provides an overview of the internal components of the treatment head 201 with the housing 206 removed. This provides an overview of one or more printed circuit boards (PCBs) 224 and / or electrical connections 226, which can be configured to provide on-board electrical connections to the treatment head and / or other electrical components, respectively. Additionally, one or more encoders 227 can be provided to track the rotational and / or axial movement of the imaging probe. In the illustrated embodiment, only a single encoder 227 is shown to track the axial movement of the imaging probe. In some embodiments, measured information from one or more encoders can be used to update the position of the treatment head, imaging probe, and / or therapy transducer in real time. In other embodiments, encoded information about the position and orientation of the imaging probe can be used by the histotripsy therapy system to register images captured by the imaging probe with the robot's position coordinate system, a digital treatment plan, and / or other images (e.g., MRI, CT, etc.). Thus, the encoder information can be used to support fusion of ultrasound images with another imaging modality (e.g., CT / MRI, or other medical imaging). 2B further illustrates a coupling assembly 230 that can be configured to provide coupling between an ultrasound imaging probe (not shown) and a therapy head. The coupling assembly can facilitate both rotation and axial translation of the ultrasound imaging probe relative to the therapy transducer / therapy head. The clearance between the coupling assembly 230 and the bore of the therapy head can be very tight to ensure very precise tracking and movement of the imaging probe / coupling assembly relative to the therapy transducer array.

[0137]

[0143] As briefly described herein, the therapy head may include position encoders for rotation and translation, including cable routing and I / O interfaces, as well as support for rapid exchange with an encoded robotic arm and other mechanical components to ensure the imaging probe maintains proper alignment within the central bore of the therapy transducer. These can provide incremental position feedback (typically for a single position sensor) or absolute position feedback over an allowable range for each degree of freedom. Additionally, probe position status may be displayed through the system software and user interface. In motorized embodiments, the user can interact with various physical controls (e.g., dials) and / or software controls (via a software user interface) to manipulate and control the probe position. Furthermore, these controls may be located in various locations on the system (e.g., a display control panel, a wireless remote controller, etc.).

[0138]

[0144] In terms of the electrical design, representatively and in embodiments for manual translation, the input to the PCB can include a position sensor for translation, which may comprise a laser position sensor for tracking the distance to the stage that moves the geared shaft up and down as the probe is translated axially. The target of the laser can be the stage itself. The sensor connects to the powered treatment head PCB and provides an analog voltage output based on the stage position. Both rotational and translational position encoders may be included. These can provide incremental position feedback (typically for a single position sensor) or absolute position feedback over an allowable range for each degree of freedom. Encoders can be included in the mechanical design to directly measure the movement of the imager tube, either directly on the motor shaft or anywhere along the mechanical linkage between them.

[0139]

[0145] In FIG. 2B, an encoder 227 (e.g., a linear encoder) may be located within the treatment head. The linear encoder may be a laser encoder and provided in a proximal portion of the treatment head (e.g., near the robotic coupler 214). The location of the linear encoder here allows for minimal interference with other mechanical elements of the treatment head. Furthermore, this portion of the treatment head is typically not submerged or in contact with the acoustic coupling medium, thus keeping the components dry. In some embodiments, the encoder may use a laser to determine the distance between the ultrasound imaging probe (e.g., including a stage or coupler attached to the ultrasound imaging probe) and the encoder. This distance may be communicated as a voltage to the robot / Histotripsy system and displayed to the user on a UI screen. This distance may also be incorporated into patient planning and treatment using Histotripsy.

[0140]

[0146] 2G-2I show a second encoder 242 (e.g., a rotational encoder) located at the distal portion of the treatment head (e.g., near the ultrasound imaging probe). The encoder can be electrically connected to a PCB (e.g., PCB 224 in FIG. 2B), which is powered and provides an analog voltage output based on the rotation of the rotor 244 and stator 245. The rotor 244 can be attached to a keyed plate 246 that rotates with the ultrasound imaging probe while the stator remains fixed. Notably, the stator and rotor components are magnetic, providing feedback on the relative rotation of the rotor with respect to the stator. Rotational information is sent to the robot via a rotational encoder cable 248 that extends through the handle and can be connected to the PCB 224. A chassis 243 is shown above the stator 245 and surrounds the linkage assembly 230. The chassis is configured to form a connection with the grip base, described below. Collectively, the chassis, grip base, and adapter plate (also described below) form a connection between the therapy transducer array and the remainder of the therapy head, which for ease of discussion may be referred to herein as a connection between the therapy transducer array and the therapy head housing.

[0141]

[0147] In some embodiments, referring to FIG. 2H , rotation of the ultrasound imaging probe (such as by a rotating collar / collar 221) activates a pawl 247 that can be positioned at periodic locations around a keyed plate 246 (e.g., 0 degrees, +90 degrees, and −90 degrees) to provide tactile feedback to the user at the specified angle of rotation.

[0142]

[0148] Some embodiments can include one or more free-drive membrane switches connected into the PCB that provide a digital output when pressed / activated. There can be at least one button on each of the two handles of the treatment head. The PCB can then be designed so that when either of these buttons is pressed, it sends a digital signal to the robot positioning system to activate the free-drive.

[0143]

[0149] From an output perspective, a Lumberg cable can be used as the connector protruding from the PCB connecting it to the robot I / O. Through this connection, all electronic components are powered and there are two analog outputs to the robot (linear and rotary encoders) as well as two digital outputs (limit switches and free-drive button).

[0144]

[0150] FIG. 2D is a cross-sectional view of the therapy head, including showing the imaging probe and linkage assembly 230 of the therapy head, in addition to various other features previously described above, including the imaging probe control 212, PCB 224, and encoder 227. Linkage assembly 230 is described in detail below. Additionally, FIG. 2D shows linear motion coupler 229, which is a platform configured to translate axial movement of a mechanical linkage associated with linkage assembly 230 to enable axial movement of the imaging probe. Further details are provided herein with respect to FIG. 2E.

[0145]

[0151] One or more bearings 231 can be located near the base of the handle to provide a precision fit between the linkage assembly 230 and the bore of the treatment head. Briefly, the linkage assembly 230 provides mechanical support to the imaging probe, allowing axial and rotational translation and rotational alignment of the imaging probe while providing support to the imaging probe.

[0146]

[0152] The coupling assembly 230 is illustrated in at least FIG. 2F and described in more detail herein. As previously described, the primary function of the coupling assembly is to provide a precision connection between the ultrasound imaging probe 204 and the treatment head (not shown, but illustrated in at least FIGS. 2A-2E). In particular, the coupling assembly 230 can include a housing 233, an exhaust assembly 228, a float plate 266, a tube cap 267, and a linear motion coupler 229. While the housing is shown as a tubular structure, other shapes or configurations are within the scope of the present disclosure. In some embodiments, the linear motion coupler 229 can include both the tube cap 267 and the float plate 266 in a unitary structure.

[0147]

[0153] The exhaust assembly of the coupling assembly can be configured to exhaust air and / or fluid from a distal portion of the therapy head when the therapy head is submerged in a fluid, such as an acoustic coupling medium. Some or all aspects of the coupling assembly can be fabricated from a non-expansion or zero-expansion material, such as aluminum. In one embodiment, the housing 233 comprises a non-expansion material. In particular, the housing can be constructed entirely of aluminum. A non-expansion material does not expand, contract, or change dimensions in response to contact with a fluid, such as submersion in an ultrasonic coupling medium. Other components of the therapy head and / or coupling assembly may also be waterproof, water-resistant, or non-expansion.

[0148]

[0154] While the various components of the linkage assembly are individually labeled and described herein, it should be understood that some or all of the components can be integrated. For example, it is envisioned that the entire linkage assembly, including the exhaust assembly, can be formed from a single, integral piece (e.g., by injection molding). The previously described bearings of the therapy head can be configured to align the outer diameter of the linkage assembly 230 with the inner diameter of the bore in the therapy head or therapy transducer array. The tight tolerances provided by the bearings between the linkage assembly 230 and the bore ensure a precision fit between the linkage assembly 230 and the bore such that the imaging probe can track axially along the bore without any lateral movement, ensuring that the focal direction of the transducer array remains consistent.

[0149]

[0155] 2E and 2O show a mechanical implementation of the imaging probe control 212. In this embodiment, the imaging probe control 212 can include a shaft (e.g., shaft 262 in FIG. 2O) coupled or connected to a gear 232. Rotation of the imaging probe control 212 and shaft results in rotation of the gear 232, which engages with a geared shaft 234. The geared shaft (straight thread) 234 can be threaded and configured to engage with corresponding threads on a shuttle assembly 236. Rotation of the geared shaft 234 can move the shuttle assembly 236 axially along the geared shaft. In some examples, the shuttle assembly can include an extension arm 237, which can include a protrusion or rod 239 configured to ride along a track 241. The rod 239 and track 241 can ensure smooth and consistent axial movement of the shuttle assembly when the imaging probe is translated. While the shuttle assembly and extension arm are shown as two separate components linked together in this example, it should be understood that other embodiments may include a single-piece shuttle assembly integrated with the extension arm and rod. The linear motion coupler 229 (of the linkage assembly) can be fixedly attached to the shuttle assembly. In this configuration, rotation of the imaging probe control 212 can thus cause the shaft of the shuttle assembly, the linkage assembly, and thus the imaging probe to advance. The imaging probe can be disposed within the linkage assembly. In some embodiments, the linkage assembly includes an exhaust assembly configured to receive the imaging probe shaft, which fits snugly around the geometry of the probe handle / shaft. The linkage assembly is configured to translate / rotate within the central bore of the therapy transducer. The linkage assembly can include or be attached to the linear motion coupler 229, which is comprised of a tube cap 267 and a float plate 266.The float plate 266 is attached to the tube cap 267 in a manner that allows a small amount of movement horizontally / laterally between the tube cap and shuttle assembly while maintaining a tight connection axially between the two. This allows the linkage assembly in the translating stack to maintain vertical alignment with the transducer bore allowing for a small amount of horizontal space to move as needed to translate freely, without being restricted by the alignment and tolerances of the components mentioned above.

[0150]

[0156] While Figure 2E provides a mechanical / manual implementation of the axial and rotational movement of the imaging probe, it can be understood how the treatment head can be modified to provide automatic or electronic control of the imaging probe. For example, a first motor may be coupled to a gear 232 via a shaft, and rotation of the imaging probe control 212 may be used to control the rotation of the motor and thus the gear 232, which then translates the rotational motion into linear motion by moving the shuttle assembly along a geared shaft 234. A similar mechanism may be implemented for rotation by coupling a second motor to a second geared shaft that runs along the center of the linkage assembly and couples directly to the probe handle or to another rigid feature of the linkage assembly. In this way, rotation of the imaging probe control (or another knob or control) may result in rotation of the second shaft and therefore rotation of the imaging probe.

[0151]

[0157] Manual rotation of the imaging probe can be controlled with a rotating sleeve 221 as illustrated in at least FIGS. 2A, 2F, and in more detail in FIG. 2J. Referring to FIG. 2F, the coupling assembly 230 can include a slot, rail, groove, or other engagement feature 234 configured to engage with a corresponding engagement feature or key in the rotating sleeve (e.g., the rotating sleeve 221 of FIG. 2A). For imaging probe rotation, a slot in the coupling assembly 230 is keyed to the rotating sleeve 221, which the user can rotate + / - 90 or + / - 180 degrees. The slot 234 can extend along the vertical length of the coupling assembly to allow the imaging probe to be rotated anywhere along the probe's translation. FIG. 2F also shows an exhaust assembly 228 disposed or positioned within the coupling assembly 230. While the exhaust assembly 228 is generally shown and described as being part of the coupling assembly 230, it should be noted that in some embodiments, the exhaust assembly may be separate from the coupling assembly. Additionally, while the exhaust assembly 228 is illustrated as being a separate component fitted within the coupling assembly, the exhaust assembly 228 and the coupling assembly may be an integrated or monolithic structure in other embodiments. In still other embodiments, the exhaust assembly and a portion of the coupling assembly, such as a tube cap, may also be a single monolithic structure. While the exhaust assembly 228 is described as part of the coupling assembly 230, it should be understood that the coupling assembly and the exhaust assembly generally work together to facilitate placement of the ultrasound imaging probe within the therapy transducer array and to manage the removal of air bubbles and / or fluid from the therapy head when the therapy head is submerged in a coupling medium or fluid.

[0152]

[0158] 2J, there is shown how slot 234 of linkage assembly 230 interacts with key 250 on rotating sleeve 221. The slot / key arrangement allows for axial translation of linkage assembly 230 relative to rotating sleeve 221 while still allowing for rotational control regardless of axial position.

[0153]

[0159] 2K and 2L additionally show how bearings 231a and 231b (which maintain a snug clearance with coupling assembly 230) are secured or surrounded by grip base 252 and adapter plate 254, respectively. Additionally, adapter plate 254 can be coupled to therapy transducer array 202 as shown. Furthermore, adapter plate 254 and grip base 252 are connected to each other through chassis 243. The connection between the adapter plate, grip base, and chassis forms a connection between the therapy transducer array and the remainder of the therapy head. For ease of discussion, the connection between the therapy transducer array and the remainder of the therapy head may be referred to herein as a connection between the therapy transducer array and the therapy head housing.

[0154]

[0160] Referring to FIG. 2M, the rotating sleeve 221 further includes tabs 221a disposed along an outer portion of the sleeve 221. The tabs 221a can be disposed, for example, 180 degrees apart on the rotating sleeve. The tabs 221a can be manipulated by the user for sleeve rotation and can provide the user with a visual indication of the orientation of the probe on the therapy head. The tabs 221a can be configured to align with the orientation of the ultrasound imaging probe. In some embodiments, the horizontal axis AA of the imaging probe head can pass through the tabs 221a. In some examples, one or more notch features 221b can be disposed on at least one of the tabs 221a. The notch feature 221b can be used to instruct the user not to submerge the therapy head in the coupling medium past or above the notch feature 221b to protect the accuracy of the linear position encoder.

[0155]

[0161] In another representative example of a treatment head design with motorized probe rotation and translation, the design may include the following major components and mechanisms: The ultrasound imaging probe may be mounted within the linkage assembly so that the center of the imaging plane is aligned with the central axis of the linkage assembly. The therapy transducer may include a cylindrical bore (contained within its own housing or rigidly mounted to its own housing) whose axis is aligned with the therapy beam axis. The inner diameter of this bore may be configured to match (within slip tolerances) the outer diameter of the linkage assembly. This becomes the shared axis for imaging and therapy, and alignment between the imaging axis and the therapy axis is maintained through both degrees of freedom of the cylindrical engagement (imager rotation around this axis and imager translation along this axis). Relative motion between these two components can be achieved via an electric motor. The motor for moving the imager along the rotational degree of freedom may be coupled to the imager tube directly, or independently of the translational motion by coupling rotation via an axially keyed or slotted shaft. The motor for moving the imager along the translational degree of freedom can be coupled to the imager tube directly, or independently of the rotational motion by coupling the translation via a circumferentially keyed shaft. If both motors are to be fixed (easier to wire), one of the shafts must be coupled independently of the other.

[0156]

[0162] Several possibilities exist for providing feedback about the imager's position. The simplest form is a single position sensor. This can be a mechanical switch or other contact / non-contact sensor that changes signal when the imager reaches a position of interest along one of the degrees of freedom. More specifically, the imaging probe's position can be read by a position sensor, home switch, or contact switch 256, as illustrated in FIG. 2N. When the imaging probe 204 is in the unextended position, the imaging probe is fully retracted toward the transducer in the home position. In one embodiment, and as illustrated in FIG. 2N, when the imaging probe is fully retracted, a set screw 258 contacts a lever 260, initiating a binary on / off signal from the home switch. The imaging probe's home position is communicated to the user and the robot through a digital output triggered at the switch. When the imaging probe is unextended or retracted, it is outside the therapy path so that no histotripsy pulses pass through the ultrasound probe. When the imaging probe is extended for patient viewing and planning, the home switch lever will be released and the signal will change to "off." The UI can display the imaging probe translation or extension and rotation to the user. In embodiments, patient therapy cannot occur until the home switch detects that the imaging probe is fully or partially retracted so that it is clear of the transducer histotripsy pulse. For example, the system's electronic controller or processor can be configured to prevent the initiation of histotripsy therapy unless the ultrasound imaging probe is retracted to a specified position (e.g., fully retracted, partially retracted, or retracted sufficiently so as not to block or interfere with the histotripsy pulse from the therapy transducer array).Although the illustrated embodiment provides a physical switch to determine whether the ultrasound imaging probe is retracted, other embodiments are provided that include sensors that do not require physical contact or connection. For example, a laser, infrared (IR), or other similar sensor can be used to determine the axial position of the imaging probe and / or whether the imaging probe is retracted, extended, or in a position that does not obstruct or substantially obstruct the therapy transducer elements of the therapy array.

[0157]

[0163] Details regarding the mechanical coupling strategy may influence which strategy may be preferred. For example, measuring at the motor shaft is typically simplest because many motors include encoders, but any mechanical slippage, contraction, or recoil will result in inaccuracies in the imager's reading relative to its true position. Motors may also require appropriate controllers to achieve precise positioning. These controllers can be local to minimize wiring / connections in the treatment head. These motor controllers are also typically controlled by a master cooperative motion controller. This master controller would then handle all communication with the system via a single communication channel, coordinating and controlling all local motors, controllers, sensors, encoders, etc. The master controller may be integrated into the treatment head itself or configured / integrated into another subsystem of the overall Histotripsy system, with communication provided through or with the robot IO or other IO interfaces of the system.

[0158]

[0164] In another example treatment head design, a manual and / or motorized rotating and translating probe treatment head can be used to perform controlled, robotically enabled ultrasound sweeps to enable the alignment of tracked ultrasound data and multimodal image registration of live-streaming ultrasound with a set of reference images, including, but not limited to, MRI, CT, PET / CT, ultrasound, and / or other modalities. The sweeps and associated data can be used to build, deform, register, and augment 2D multi-planar data into a deformable 3D model. The system and supporting software can also be enabled to display treatment plan contours within these datasets (2D, 3D, and various overlays and views). In terms of treatment plan and treatment parameters, the system can be configured to auto-populate a grid array of focal locations (e.g., bubble cloud locations) of various sizes, numbers, spacing, etc., as well as built-in logic / control for selected sequences and therapy parameters by focal location and application / indication, etc.

[0159]

[0165] Referring again to FIG. 2F, FIG. 2F provides a diagram of the imaging probe 204 including the linkage assembly 230. The linkage assembly 230 provides mechanical support as well as axial and rotational alignment for supporting the imaging probe. In particular, the linkage assembly described herein can include an exhaust assembly 228, a housing 233, a linear motion coupler 229, a float plate 266, and a tube cap 267. The exhaust assembly 228 can be disposed within the housing 233. Other embodiments are envisioned in which the linkage assembly does not include an exhaust assembly. As shown, the handle (or shaft) of a typical ultrasound imaging probe is much shorter than necessary for the present application; therefore, the linkage assembly 230 can be sized and configured to fit over and partially around the probe handle, and to extend from a bore in the therapy head to the linear motion coupler to provide appropriate spacing between the handle / controls of the therapy head and the bore in the therapy head. This results in a cavity 264 being formed in the linkage assembly 230 proximal to the exhaust assembly 228. Coupling assembly 230 can be attached to exhaust assembly 228 with screws 232 or adhesive, for example. Additionally, referring to FIG. 2F, coupling assembly 230 can include slots, rails, grooves, or other engagement features 234 in housing 233 configured to engage with corresponding engagement features in a rotating sleeve (e.g., rotating sleeve 221 of FIG. 2A). For rotation of the imaging probe, slot 234 in coupling assembly is keyed to the rotating sleeve, which can be rotated + / - 90 or + / - 180 degrees by a user. Slot 234 can extend along the vertical length of coupling assembly so that the imaging probe can be rotated anywhere along the translation of the probe.In some embodiments, the linkage assembly and / or linear motion linkage (e.g., linear motion linkage 229 in FIG. 2D ) activates pawls located at 0, +90, and −90 degrees to provide tactile feedback to the user at specified rotation angles. Linkage assembly cavity 264 is completely covered by a tube cap 267 located at its proximal end. An opening 268 can be provided in linkage assembly 230 for routing electrical wires to the imaging probe.

[0160]

[0166] FIG. 2Q is a bottom-up view of the exhaust assembly 228. As described above and herein, the exhaust assembly 228 can be configured to be placed on, disposed within, or attached to the housing 233 of the coupling assembly 230. In some embodiments, the exhaust assembly 228 is a unitary component, while in other embodiments, the exhaust assembly 228 is comprised of multiple parts. In the illustrated embodiment, the exhaust assembly 228 comprises first and second halves 238a and 238b. Overall, the exhaust assembly 228 forms a bore 240 designed and configured to precisely match the outer diameter of the imaging probe shaft or handle. The tolerance between the outer diameter of the coupling assembly 230 and the bearings (e.g., bearings 231a and 231b) in the therapy head can be very close to maintain an airtight and / or watertight seal between the coupling assembly and the therapy head while still allowing rotation and / or axial translation of the imaging probe.

[0161]

[0167] The exhaust assembly 228 can include one or more exhaust holes 242a-242d positioned at or around the bore 240 and relative to the mating surface / outer diameter of the imaging probe (e.g., relative to the probe handle or shaft). In the illustrated embodiment, the exhaust assembly includes four exhaust holes, with exhaust holes 242a and 242b formed in each of the halves 238a and 238b, and exhaust holes 242c and 242d formed at the intersection between the halves 238a and 238b. It should be understood that other embodiments can include fewer or more than four exhaust holes. The exhaust holes 242a-242d can serve multiple purposes, including allowing air bubbles captured by portions of the therapy head, such as the therapy transducer array, imaging probe, and / or exhaust assembly 228, to be exhausted from the therapy head when the therapy head is submerged in the acoustic coupling medium, and further allowing the acoustic coupling medium to flow out of the therapy head after the therapy head is removed from the coupling medium or after therapy. The vents are channels configured for air / bubble relief and liquid / connection assembly media relief.

[0162]

[0168] As shown in Figure 2Q, exhaust holes 242a and 242b are spaced approximately 180 degrees apart from another exhaust hole, and exhaust holes 242c and 242d are spaced approximately 180 degrees apart from another exhaust hole. Overall, the exhaust holes are located approximately every 90 degrees around hole 240 in the embodiment of Figure 2Q. It should be understood that other embodiments can have a different number of exhaust holes spaced at regular or irregular intervals around hole 240.

[0163]

[0169] As shown in FIG. 2Q, the exhaust assembly can further include a beveled, sloped, or concave section 249, which can be configured to direct air bubbles and / or acoustic coupling medium toward the exhaust hole. The beveled section 249 can be located near the distal end or surface of the exhaust assembly and / or coupling assembly. In the illustrated embodiment, the exhaust holes are implemented as opposing pairs on either side of the bore 240. In some embodiments, the exhaust holes can be implemented in the distal surface of the exhaust assembly to feed the beveled or concave section. In other embodiments, the exhaust holes can be implemented along the beveled section or at the proximal end or portion of the beveled section.

[0164]

[0170] In some embodiments, one or more of the exhaust holes can be fluidly connected to a channel extending into and along the longitudinal axis of the bore toward the robot arm. In FIG. 2Q, exhaust holes 242a and 242b are located along central portions of first half 238a and second half 238b of the linkage assembly, respectively. In some embodiments, the exhaust holes extend longitudinally the entire length of the exhaust assembly. In other embodiments, the exhaust holes only extend partially into the exhaust assembly. In some embodiments, one or more exhaust holes extend along the entire length of the exhaust assembly, with one or more exhaust holes stopping or terminating before the proximal end of the exhaust assembly. Although not illustrated, it is also contemplated that an exhaust hole may be combined with another exhaust hole along at least a portion of the longitudinal axis of exhaust assembly 228. It should be understood that embodiments are provided in which exhaust holes and / or channels extend partially into the exhaust assembly, along the entire length of the exhaust assembly, or anywhere in between.

[0165]

[0171] FIG. 2R shows a view of the inside of the first half 238a of the exhaust assembly. The exhaust hole 242a of the first half 238a is shown with a channel 270. The channel can provide a fluid and / or air bubble path for fluid and air bubbles to travel along the exhaust assembly (e.g., through a connection assembly) to and from the therapy head. In this embodiment, the channel from the exhaust hole 242a extends along the entire length of the exhaust assembly from the proximal end to the distal end. The exhaust holes 242a, 242b each extend into and are in fluid communication with the channel 270. Fluid and air or other gases can flow from the exhaust hole and into the channel, or out of the channel and out of the exhaust hole. In other embodiments, the channel 270 from the exhaust hole 242a extends only partially along the longitudinal length of the exhaust assembly. Figure 2S is another view of the connection assembly including housing 233 and first and second halves 238a and 238b of the exhaust assembly inside housing 233. Figure 2S also shows a channel 270 in the exhaust assembly.

[0166]

[0172] FIG. 2T shows the connection assembly 230 with a tube cap 267 disposed at the proximal end of the connection assembly 230 to completely cover the cavity, and a float plate 266 mounted to the tube cap. Screws (not shown) can be used to mount the tube cap and float plate together. As shown, the tube cap 267 and float plate 266 can include multiple vent holes 272. This design allows air and / or fluid to flow through the cavity 264 formed between the connection assembly and the exhaust assembly, along the longitudinal length of the channel, into the exhaust holes of the exhaust assembly, and exit the connection assembly through the vent holes 272. The float plate 266 is configured to allow lateral translation of the connection assembly within the treatment head as the assembly moves axially. In some embodiments, the screws holding the tube cap and float plate together can be compacted or reduced in diameter to allow movement of the float plate. As illustrated, the vent holes 272 are formed by aligning openings or holes in the tube cap to align with openings or holes in the float plate. While three vent holes are shown in FIG. 2T, fewer or more holes / vent holes are within the scope of the present disclosure. Generally, the channels and vent holes of the coupling assembly are also in fluid communication with the previously described drainage channels (e.g., drainage channel 218) of the treatment head. Thus, air or fluid vented into the treatment head can flow through the treatment head and exit through the drainage channels (e.g., drainage channel 218) or through the vent holes in the float plate. This protects any sensitive electronic components from seizing or being adversely affected by contact with the fluid and also allows air bubbles to be removed from the surface of the treatment head.

[0167]

[0173] Referring again to FIG. 2R, the first half 238a of the exhaust assembly 228 is shown, including portions of the exhaust holes 242c and 242d formed therein. As previously described, the exhaust holes 242c and 242d are formed at the interface between the first and second halves of the exhaust assembly and are therefore not fully shown in this illustration. Nevertheless, FIG. 2R further illustrates how, in some embodiments, one or more of the exhaust holes (e.g., exhaust holes 242c and 242d) can be configured to direct or divert fluid and / or air from the exhaust hole through a radiating opening 274 in the exhaust assembly. The radiating opening 274 in the exhaust assembly can be aligned with a corresponding opening (not shown) in the connection assembly. In some embodiments, the radiating opening can allow the exhaust of air bubbles or fluid from the exhaust hole, out of the connection / exhaust assembly, and out of the treatment head through the drain 218 (described above). FIG. 2R shows a portion of the radiant opening 274 formed by the first half of the exhaust assembly, and FIG. 2U shows the complete exhaust assembly with the radiant opening 274 on the side of the assembly. Thus, in some embodiments, one or more of the exhaust holes can be configured to direct or divert fluid and / or air radially through the opening in the exhaust assembly. As previously described, other embodiments can include vent holes configured to direct or divert fluid and / or air axially / longitudinal through the opening in the linkage assembly (e.g., through the exhaust assembly, into the cavity of the linkage assembly, and out through the vent holes in the tube cap and / or float plate). Other embodiments can include a combination of directing fluid and / or air both axially and radially from the linkage assembly.

[0168]

[0174] In some embodiments, the therapy head and / or imaging probe can be moved, rotated, pushed aside, or controlled to rapidly vibrate or move to encourage or cause any remaining air bubbles on the therapy head, exhaust assembly, coupling assembly, and / or imaging probe to be removed and directed toward the exhaust holes of the exhaust assembly. This can be done after the therapy head is submerged or partially submerged in the acoustic coupling medium.

[0169]

[0175] As mentioned above, bearings 231a and 231b (which maintain a tight clearance with coupling assembly 230) are secured or surrounded by grip base 252 and adapter plate 254, respectively. FIG. 2V shows another view of therapy transducer 202 including adapter plate 254 configured to couple the therapy transducer to the rest of the therapy head. More specifically, liquids, such as coupling media, can also be drained from the therapy head by additional features of the adapter plate. The adapter plate can be skeletonized to reduce weight. Such skeletonization can form a pocket 278 in the adapter plate. To avoid fluid collection in pocket 278, the adapter plate can further be mounted on a support so that it is positioned above the therapy transducer, at least partially spaced from the therapy transducer surface (e.g., by up to 1 mm or more unless the adapter plate is attached or connected to the therapy transducer), providing a gap for liquid to pass out of pocket 278 and toward and from drainage channel 218 of the therapy head. In particular, drainage channels 218 are positioned adjacent to the therapy transducer array and between the therapy transducer array and the therapy head housing. FIG. 2W is a side view of the therapy transducer and adapter plate 254, showing a strut-mounted gap 280 between the adapter plate and the transducer to allow for drainage. When the therapy head is removed from the fluid, such as the coupling container / media, the fluid can flow out of the therapy head, including out of the coupling assembly / exhaust assembly, through the skeletal adapter plate, through the strut-mounted gap 280, and out of the drainage channels 218.

[0170]

[0176] FIG. 2X is an enlarged view of the drainage channel 218 previously described above. As shown, the drainage channel 218 can extend fully or partially around the circumference of the therapy array 202. The drainage channel can be formed as a slit or gap between the therapy array 202 and the therapy head housing, including at least a cover piece 209 that provides a protective cover for the coupling assembly and other components inside the therapy head, as shown in FIGS. 2U-2W. As mentioned above, the drainage channel 218 allows for the drainage / removal of fluid from the therapy head when the therapy head is removed from the fluid, such as from the coupling container. Fluid that migrates to the coupling assembly / exhaust channel while submerged in the coupling fluid / container can be removed from the therapy head 218.

[0171]

[0177] In some examples, axial translation of the imaging probe position allows the ability to modify the relative position of the therapy transducer array independent of the imaging probe position (e.g., the imaging probe remains at a fixed z-position on / near the epidermis when the therapy transducer is performing its respective treatment and motion pattern / path).

[0172]

[0178] The ultrasound imaging probe of the treatment head may be equipped or configured based on the clinical application / use case (to visualize general target location, surrounding anatomy and critical structures / adjacent organs and / or target movement relative to such, bubble clouds during calibration, test pulses, automated treatment, and post-treatment verification, etc.) As described, the imaging probe has encoded probe rotation and translation capabilities to enable multiple (including orthogonal) imaging views / perspectives via rotation, and mechanical / electrical support for the ability to see above / near the epidermis independent of the therapy transducer location via translation.

[0173]

[0179] Histotripsy therapy transducer arrays may comprise a variety of designs / geometry optimized for / by specific applications and usage requirements (e.g., abdominal targets, versus prostate, versus more superficial targets such as breast / thyroid, etc.). In some embodiments, the therapy transducer array may include various mechanical support features to interface / build the proximal side of the therapy head, including support for an integrated coaxial imaging probe in a central bore, and mechanical mounting locations for internal components, therapy head handles, housings, etc. Therapy transducers may also be uniquely electronically keyed to allow for different / application-specific usage and recognition by the system software (e.g., liver or abdominal therapy head, versus prostate, thyroid or breast, etc.).

[0174]

[0180] The therapy head provides the ability to adjust the focus and rotational orientation of the imaging probe relative to the therapy transducer array, enabling new and novel functions and treatments. For example, advancing or retracting the ultrasound imaging probe relative to the therapy transducer array allows the system to image tissue outside the target tissue volume (e.g., at greater depth) or to image very large target tissue volumes without having to move the therapy transducer array. Additionally, the ultrasound imaging probe can be moved closer to the target tissue volume to improve resolution and / or imaging quality, while the therapy transducer array can be maintained at a significant distance from the body. Furthermore, the ability to rotate the ultrasound imaging probe relative to the therapy transducer provides additional slices or views of the tissue being imaged.

[0175]

[0181] FIG. 3A illustrates an example of a therapy head 301 of a histotripsy therapy system positioned adjacent to a patient P, having a therapy transducer array 302 and an imaging probe 304. It should be understood that a coupling container and an ultrasound coupling medium would be used to acoustically couple the therapy head to the patient, but the coupling container is not shown for simplicity of illustration. The therapy transducer array 302 can have a focal point positioned within a target treatment volume 305. A real-time ultrasound image from the imaging probe 304 can be displayed on a display 307. In the illustrated example, the target treatment volume 305 can be graphically overlaid on the real-time ultrasound image. In the example of FIG. 3A, both the imaging probe 304 and the therapy transducer array are positioned away from the patient's epidermis. As a result of having to travel through an acoustic coupling medium, the resulting image from the imaging probe can include increased noise and / or lower resolution compared to placing the probe directly on the epidermis. Alternatively, if a connecting container is used to acoustically connect the treatment head to the patient, the imaging probe can be placed in contact with the connecting container or a thin film of the connecting container, which can itself be in contact with the epidermis (or separated by a layer of acoustic connecting medium).

[0176]

[0182] 3B, axial translation of the imaging probe 304 allows the probe to be placed in contact with the patient's epidermis to improve image resolution, reduce noise, and / or image at a greater depth than when the probe is fully retracted (as in FIG. 3A). Note that while the imaging probe is translated toward the patient, the focal point and target treatment volume 305 (as shown on display 307) remain in the same location.

[0177]

[0183] Referring to Figures 3C-3D, this allows for relative movement and / or rotation of the treatment head 301 while maintaining the probe in contact with the patient's epidermis to scan the target tissue volume and beyond.

[0178] Robotics

[0184] The system may comprise various robotic subsystems and components, including, but not limited to, one or more robotic arms and controllers that may further operate in conjunction with other subsystems or components of the system for delivering and monitoring acoustic cavitation / histotripsy. As previously discussed herein, the robotic arms and control systems may be integrated into one or more cart configurations.

[0179]

[0185] For example, one system embodiment can 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 listed subsystems are controlled by the user through a single bedside cart form factor.

[0180]

[0186] In other embodiments, the robotic subsystem may be configured in one or more separate carts that can be driven in a master / slave configuration from a separate master or cart, with the robot-enabled cart located at the bed / patient side and the master remote from the cart.

[0181]

[0187] The disclosed robotic arms may include multiple joints, segments, and degrees of freedom, and may also include a variety of integrated sensor types and encoders implemented for various uses and safety features. Sensing techniques and data may include, by way of example, vision, potentiometer, position / localization, kinematics, force, torque, speed, acceleration, dynamic loading, and / or others. In some cases, sensors may be used by the user to direct robot commands (e.g., gesturing the robot to a preferred setup position or gesturing to dock home). Additional details regarding robotic arms can be found in U.S. Patent Publication No. 2013 / 0255426 to Kassow et al., which is incorporated herein by reference in its entirety.

[0182]

[0188] The robotic arm receives control signals and commands from a robotic control system that may be housed on the cart. The system may be configured to provide a variety of functions, including but not limited to position, tracking, patterns, triggers, and events / actions.

[0183]

[0189] The positions can be configured to include fixed positions, pallet positions, time controlled positions, distance controlled positions, variable time controlled positions, and variable distance controlled positions.

[0184]

[0190] The tracking may be configured to include time-controlled tracking and / or distance-controlled tracking.

[0185]

[0191] The pattern of movement can be configured to include intermediate positions or waypoints and sequences of positions through defined paths in space.

[0186]

[0192] The trigger may be configured to include distance measurement means, time, and / or various sensor means, including but not limited to those disclosed herein, such as visual / imaging-based force, torque, localization, energy / power feedback, and / or others.

[0187]

[0193] Events / actions can be configured to include a variety of examples including proximity-based (approaching / moving away from a target object), activating or deactivating various end effectors (e.g., therapy transducers), starting / stopping / pausing sequences of the above events, triggering or switching between triggering events / actions, initiating patterns of movement and changing / toggle between patterns of movement, and / or time-based and temporal across defined task and time spaces.

[0188]

[0194] In one embodiment, the system includes a three-degree-of-freedom robotic positioning system that allows a user (through the system's software and associated user interface) to microscopically position the therapy transducer through an X, Y, and Z coordinate system, with the overall macroscopic positioning of the transducer (e.g., aligning the transducer over the patient's body) completed manually. In some embodiments, the robot can have six degrees of freedom, including X, Y, Z, as well as pitch, roll, and yaw. In other embodiments, the robotic subsystem can have additional degrees of freedom, allowing the robotic arm support base to be positioned along a linear axis running parallel to the general direction of the patient surface and / or the support base height to be adjusted up or down, allowing the position of the robotic arm to be modified relative to the patient, patient surface, cart, linkage subsystem, additional robots / robotic arms, and / or additional surgical systems, including, but not limited to, a surgical tower, imaging systems, endoscopic / laparoscopic systems, and / or others.

[0189]

[0195] The one or more robotic arms can also include various features to assist in manual or semi-manual manipulation and correction of arm position, which can interface on or between the therapy transducer and the robotic arm's most distal joint. In some embodiments, the features are configured to include a handle to enable one or more manual manipulations and manual controls. 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) to command various drive capabilities or modes to operate the robot to assist in global or fine positioning of the arm. The workflow for initial positioning of the robotic arm and therapy head can be configured to allow the therapy transducer / head to be positioned first in the docking solution, with the therapy transducer interfaced directly with the arm, or a different workflow allows the user to set up the docking solution first and allow the robotic arm to be interfaced with the therapy transducer / docking solution as a later / final setup step.

[0190]

[0196] In some embodiments, the robotic arm may comprise a laparoscopic, single-port, endoscopic, hybrid or combination thereof, and / or other robotic arm, and the robot of the system may be slave to a master controlling the arm and potentially multiple other arms equipped to simultaneously perform other tasks (visualization, imaging, grasping, cutting, ligating, sealing, closing, stapling, dissecting, suturing, marking, etc.), including actuating one or more laparoscopic arms (and instruments) and various histotripsy system components. For example, a laparoscopic robot may be utilized to prepare the surgical site, including manipulating the position of organs to provide more optimal acoustic access and, in some cases, further stabilizing the organs to minimize respiratory movement. In conjunction with and in parallel with this, a second robotic arm may be used to deliver noninvasive acoustic cavitation through the body cavity as observed under real-time imaging from a therapy transducer (e.g., ultrasound) and with simultaneous visualization via a laparoscopic camera. In other related aspects, similar approaches may be utilized that combine endoscopic and non-invasive approaches, as well as further combine endoscopic, laparoscopic and non-invasive approaches.

[0191]

[0197] 5A-5B, in one embodiment, the robotic arm 508 may be configured with a quick connect adapter 582 and a quick connect plate 583 to enable quick exchange of a treatment head with the robotic arm. FIG. 5A shows an exploded view of the quick connect adapter, quick connect plate, and robotic arm, and FIG. 5B shows an assembled view. The quick connect adapter 582 is configured for attachment to a distal portion of the robotic arm 508. In particular, the quick connect adapter is shaped to be received on and around the distal portion of the robotic arm 508. The quick connect plate 583 can be secured to the quick connect adapter 582, for example, with screws 585. The quick connect plate 583 is configured to interface with, engage with, attach to, or releasably connect to a robotic arm coupler (e.g., robotic arm coupler 214) described above.

[0192]

[0198] 5C-5F , quick connect adapter 582 can include a housing 584 configured to house electrical components, such as electrical component 586, which may be a socket I / O adapter cable 586 for engagement with I / O cable 516 (corresponding to I / O cable 216 described above). Electrical components 586 can extend from connection port 587 to robotic arm 508 (and ultimately to the console, processor, or controller of the Histotripsy system). These electrical components 586 carry signals from I / O cable 516 (when attached) to the robotic arm / console / cart. Electrical components 586 can be fixedly seated within adapter plate 582 with fastening features 594, such as eyelets. Housing 584 can include connection port 587 configured to receive the I / O cable.

[0193]

[0199] 5E-5F , in some embodiments, the connection port 587 can include detent features or channels 588 for alignment and selective engagement between the I / O cable 516 and the connection port 587. The I / O cable 516 can include mating features, such as one or more alignment tabs 589, which can be received in the detent features 588 of the connection port 587, thereby allowing the I / O cable 516 to be easily aligned, connected, and released. Spring-loaded retention tabs 590 can also connect to the quick connect adapter 582 to hold or keep the I / O cable 516 in place. The I / O cable 516 can be reversibly connected or mated to the connection port 587, aligning the pins (not shown) of the I / O cable with the receiving or female ends found in or on the quick connect adapter 582. In embodiments, six, eight, or more pins can be found on the I / O cable. The I / O cable 216 can be easily disconnected from the quick connect adapter 582 and removed from the connection port 587 with increased mechanical force or a rearward pull and release of the retention tabs 590. As illustrated, two retention tabs 590 are employed approximately 180 degrees apart. Other embodiments for unidirectional alignment of the I / O cable 516 to the connection port 587, such as reversing the male / female connection, are also envisioned. Additionally, visual alignment indicators may be present on one or more of the I / O cable 516 and the connection port 587. As illustrated in FIG. 5E , the I / O cable 516 includes a color indicator 591 that aligns with a corresponding color indicator 592 on the connection port 587. The cable 516 may also include a tactile feature 593 for increased or enhanced grip.

[0194]

[0200] 5C, the housing 584 may include a cover 595 disposed thereon. The cover 595 is configured to protect the electrical components 586 from any external elements and seals or encases the electrical components 586 therein. The cover 595 may be attached to the housing 584 by any technique known in the art, such as thread adhesive (as shown), welding, an interference fit, or the like.

[0195]

[0201] As mentioned above, the quick connect plate 583 can be attached to the quick connect adapter 582 via any known technique, such as screws as shown. Although illustrated with four holes, both the quick connect adapter 582 and the quick connect plate 583 can include fewer or more than four holes for attaching to one another and receiving screws therein. Other methods or techniques for attachment, such as mating features or female / male attachment mechanisms, are also envisioned. The quick connect plate 583 includes mating features that selectively engage with the robot arm coupler described above for quick exchange.

[0196] software

[0202] The system may include a variety of software applications, features, and components that allow the user to interact with, control, and use the system for numerous clinical applications. The software may communicate and work with one or more of the subsystems, including, but not limited to, therapy, integrated imaging, robotics, and other components, ancillary instruments, and accessories of the system.

[0197]

[0203] Overall, in no inherent order of importance, 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 use-related risks; treatment planning; support for various transducer configurations; robotic arms and drive systems; function generator and amplifier circuitry / slaves; test and treatment ultrasound sequences; transducer steering and positioning (e.g., electro-mechanical and electronic beam steering); treatment patterns; imaging and support for imaging probes, their manual and electro-mechanical / robotic enabled movement; imaging support for measuring / characterizing various dimensions in or around the treatment site (e.g., depth from one anatomical location to another); Features and support can be provided for pre-treatment assessments and protocols to measure / characterize the nature and condition of the in situ treatment site (e.g., acoustic cavitation / histotripsy thresholds and their variants), targeting and target alignment, calibration, autonomously, under direct observation and viewing with real-time imaging as displayed through the software including various views and viewports for autonomous viewing, marking / annotating, localizing / navigating, registering, guiding, providing and directing through workflows, treatment steps, execution treatment plans and protocols, providing communication tools (video, audio, sharing, etc.), troubleshooting, instructions, warnings, alerts, and / or enabling communication through various networking devices and protocols.It is further envisioned that the software user interface and supporting displays may comprise various buttons, commands, icons, graphics, text, etc. that enable a user to interact with the system in a user-friendly and effective manner, which may be presented in an unlimited number of permutations, layouts, and designs, may comprise two or more displays (e.g., a touchscreen monitor and 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 feature set of the system.

[0198]

[0204] Software as part of a typical system including one or more computer processors can support the various aforementioned function generators (e.g., FPGAs), amplifiers, power supplies, and therapy transducers. The software may be configured to allow a user to select, determine, and monitor various parameters and settings of the acoustic cavitation / histotripsy, and can allow the user to stop / start / modify said parameters and settings upon observing / receiving feedback on performance and status.

[0199]

[0205] The software may be configured to allow the user to select from a list or menu of multiple transducers and support automatic detection of the transducer upon connection to the system (and verification of the appropriate sequence and parameter settings based on the selected application). In other embodiments, the software may update targeting 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 an error message or warning to the user if the therapy transducer, amplifier, and / or function generator selection or parameters are incorrect or result in an error or failure. This may further include reporting details and location of such.

[0200]

[0206] In addition to the above, the software may be configured to allow a user to select treatment sequences and protocols from lists or menus and store the selected and / or previously selected sequences and protocols as associated with a unique clinical use or patient profile. The associated profile may include any associated patient, treatment procedure, clinical and / or engineering data, and may be used to inform, modify and / or guide current or future treatments or procedures / interventions, whether as decision support (e.g., using continuous data sets to build and guide new treatments) or as an active part of the treatment itself.

[0201]

[0207] As part of planning or during treatment, the software (and working with other components of the system) can enable the user to evaluate and test acoustic cavitation / histotripsy thresholds at various locations in a user-selected region of interest or predefined treatment area / volume to determine a minimum cavitation threshold throughout the region or area / volume and ensure that treatment parameters are optimized to achieve, maintain, and dynamically control acoustic cavitation / histotripsy. In one embodiment, the system allows the user to manually evaluate and test threshold parameters at various points. These points can include points at predefined boundaries, interior boundaries, and central locations / positions of the selected region of interest and treatment area / volume, and the resulting threshold measurements can be reported / displayed to the user and utilized to update therapy parameters prior to treatment. In another embodiment, the system can be configured to enable automated threshold measurements and updates, such as those enabled by the robotics subsystem described above, where the user can direct the robot or the robot can be commanded to perform measurements autonomously.

[0202]

[0208] The software may also be configured to work with a computer processor and one or more function generators, amplifiers, and therapy transducers to enable various permutations of delivering and positioning optimized acoustic cavitation / histotripsy in and through a selected area / volume. This may include systems configured in various combinations including, but not limited to, fixed / natural focus placement using purely electromechanical positioning configurations, electronic beam steering (with or without electromechanical positioning), electronic beam steering to a new selected fixed focus with further electromechanical positioning, axial (Z-axis) electronic beam steering with lateral (X and Y) electromechanical positioning, fast axial electronic beam steering with lateral electromechanical positioning, fast beam steering in 3D space, and dynamically varying one or more acoustic cavitation / histotripsy parameters (e.g., dynamically adjusting amplitude across a treatment area / volume) based on the foregoing and the ability to update treatment parameters based on threshold measurements.

[0203] Other Components, Auxiliaries and Accessories

[0209] Systems may include various other components, aids and accessories, including, but not limited to, computers, computer processors, power supplies including high voltage power supplies, controllers, cables, connectors, networking devices, software applications for integration into security, communications, 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, phones, Internet of Things enabled capabilities, special use "apps" or user training materials and applications (software or paper-based), virtual proctors or trainers and / or other enabling features, devices, systems or applications, and / or methods of using the above.

[0204] Treatment Head Methods / Uses and Examples

[0210] In addition to performing a wide range of procedures, the system may enable additional benefits to assist the user, such as enhanced planning, imaging, and guidance. In one embodiment, the system may enable the user to create patient-, target-, and application-specific treatment plans, which may be configured to optimize treatment parameters based on feedback to the system during planning, which may further include the ability to run various test protocols to gather specific inputs to the system and the plan.

[0205]

[0211] The feedback may include various energy, power, location, position, texture and / or other parameters.

[0206]

[0212] The system and the above feedback may also be further configured and used to autonomously (and robotically) execute the delivery of optimized treatment plans and protocols, and start / stop / modify treatment at the user's discretion, as visualized under real-time imaging during the procedure, allowing the user to directly observe the localized treatment tissue effects as the treatment progresses. Both testing and treatment protocols may be updated during the treatment at the direction of the user, or in some embodiments based on logic built into the system.

[0207]

[0213] It is also recognized that many of these benefits can further improve other forms of acoustic therapy, including high intensity focused ultrasound (HIFU), including boiling histotripsy (thermal cavitation), and thermal ablation with high intensity therapeutic ultrasound (HITU), and are considered part of this disclosure. The present disclosure also contemplates the application of histotripsy as a means to activate previously delivered active drug payloads that are inactive, either through protection in micelles, nanostructures, or similar protective structures, or through molecular arrangements that allow activation only upon application of acoustic energy.

[0208]

[0214] In another embodiment, a therapy subsystem, comprising in part one or more amplifiers, transducers, and power sources, may be configured to enable a multitude of acoustic cavitation and histotripsy driving capabilities that provide unique benefits based on application, method, and / or patient-specific usage. These benefits may include, but are not limited to, the ability to better optimize and control treatment parameters, which may enable more desirable thermal profiles, delivery of more energy with increased treatment speed and reduced procedure times, electronic beam steering, and / or other features.

[0209]

[0215] The present disclosure also includes novel systems and concepts, such as those relating to systems and subsystems with new and "universal" amplifiers that can enable multiple drive approaches (e.g., single and multi-period pulsing), which in some embodiments may include various novel features to further protect the system and user from electrical safety or other threats (e.g., adverse effects on transducer and / or amplifier circuitry).

[0210]

[0216] In another aspect, the system and therapy subsystem can include a large number of therapy transducers, configured for specific applications and uses, adapted for treatment across a wide range of working parameters (target size, depth, location, etc.), and capable of including a wide range of working specifications (described in more detail below). The transducers can be further adapted, interfaced, and connected to a robotic-enabled system, as well as a coupling subsystem that allows the transducer to be positioned in or with an acoustic coupling device that, in many embodiments, enables simultaneous imaging and histotripsy treatment through an acceptable acoustic window. The therapy transducers can also include an integrated imaging probe or localization sensor capable of displaying and determining the transducer's position within the treatment site, providing a direct view (or representation) of the treatment site, and such that acoustic cavitation / histotripsy tissue effects and bubble clouds may or may not change in appearance and intensity throughout the treatment, and depending on their location within the treatment (e.g., tumor, surrounding healthy tissue, critical structures, fatty tissue, etc.).

[0211]

[0217] The systems, methods, and uses of the systems disclosed herein may be beneficial in overcoming significant unmet needs in the areas of soft tissue ablation, oncology, cancer immunology, advanced image-guided procedures, surgical procedures including, but not limited to, open, laparoscopic, single-incision, transluminal, endoscopic, non-invasive, and various combinations thereof, various interventional spaces for catheter-based procedures in the vascular, cardiovascular pulmonary, and / or neuroscience spaces, cosmetic / aesthetics, metabolic (e.g., type 2 diabetes), plastic and reconstructive, vision and ophthalmology, orthopedics, gynecology, and human health, and other systems, devices, and methods for treating diseased, injured, unwanted, or healthy tissue, organs, or cells.

[0212]

[0218] Systems and methods are also provided for improving treatment patterns within tissue that can reduce treatment time, improve efficacy, and reduce the amount of energy and focused tissue heating delivered to the patient.

[0213]

[0219] Methods and uses of a treatment head including a translatable / rotatable imaging probe are also provided herein.

[0214]

[0220] For example, referring to Figure 4, a flowchart illustrating a method of using the above-described treatment head is illustrated. Referring to step 402, the treatment head of the Histotripsy system can be placed in acoustic communication with a patient. For example, the treatment head can be mounted on a robotic positioning system and manipulated or guided (manually or automatically) into a coupling container configured to acoustically couple the treatment head to the patient's epidermis.

[0215]

[0221] Next, the therapy focal point of the therapy transducer can be aligned with the target tissue volume to be treated in step 404. In some embodiments, the focal distance of the therapy transducer is known and fixed, and thus the robotic positioning system can position the therapy transducer from the target tissue volume by this known focal distance.

[0216]

[0222] In step 406, the ultrasound imaging probe can be axially extended, advanced, or shortened toward the target tissue volume to enable imaging and treatment planning. In some examples, the ultrasound imaging probe can be advanced so that it is in contact with the patient's epidermis, while the therapy transducer is not in contact with the patient's epidermis. Positioning the imaging probe closer to the target tissue volume than the therapy transducer allows for a better overview of the target tissue, including improved spatial and contrast resolution, and can be used to remove reflection artifacts cluttering the image.

[0217]

[0223] In step 408, the method further includes moving the therapy head to implement the treatment plan while the ultrasound imaging probe is axially extended or advanced, which allows movement of the therapy transducer to scan the tissue volume while maintaining epidermal contact with the ultrasound imaging probe (or a shortened state of the probe).

[0218]

[0224] In step 410, the method may include retracting the ultrasound imaging probe to a fully retracted position and initiating histotripsy therapy. In some embodiments, a switch may be activated when the imaging probe is fully retracted to indicate to the system the position of the ultrasound imaging probe (e.g., fully retracted). In some embodiments, initiating histotripsy therapy while the ultrasound imaging probe is retracted may result in one or more of the therapy transducers being blocked by the ultrasound imaging probe. Retracting the probe still allows for real-time visualization of the target tissue volume, but removes any potential therapy obstruction.

[0219]

[0225] In some embodiments, referring to FIG. 4 , the ultrasound imaging probe can be retracted back toward the therapy transducer during therapy treatment. Yet, in another embodiment, the imaging probe can be maintained in a shortened position during therapy. This fixes the imager in the shortened position for better visualization of the target tissue and Histotripsy bubble cloud for treatment planning. Note, however, that in this embodiment, depending on how far the probe is advanced, the imaging probe can potentially block some of the therapy transducers from delivering Histotripsy pulses to the tissue. Optionally, as a hybrid of the two approaches described above, the imaging probe can be shortened from the therapy transducer during treatment planning, but then retracted back a little (but not completely) based on the size of the target tissue volume or treatment plan so as not to completely block the therapy pulses from reaching the intended target. This configuration balances improved imaging quality with reduced registration / blocking issues.

[0220]

[0226] Usage examples are also provided.

[0221]

[0227] Example 1

[0222]

[0228] In a representative example, the novel treatment head system is configured to allow axial translation (e.g., shortening) of the imaging probe near / far from the epidermis / body for planning purposes to provide more optimal image quality, and then orient the imaging probe to a retracted "home position" for the remainder of the procedure. When the imaging probe is in the "home position," a home switch is initiated, communicating to the robot that the imaging probe is in the retracted position. Histotripsy therapy can then be initiated. In this example, this would enable enhanced visualization of the target (and target location) during therapy planning, including improved spatial and contrast resolution, and may be used to remove / reduce reflection artifacts cluttering the image. In this example, the system software would be configured to ensure the location of the planning contours (target and margins) and associated geometries / locations are accurate and may include features for forcing / guarding potential changes, including forcing the probe to remain in a locked position during various phases of the procedure as displayed / monitored via the software UI.

[0223]

[0229] Example 2

[0224]

[0230] In another representative example, the translation features of the therapy head and probe can be used to translate or "shorten" variously from the planning phase and throughout treatment, including automated therapy. As in the previous example, this would not only enhance visualization during planning, but also provide enhanced real-time visualization and treatment monitoring (of the target, target tissue location, and Histotripsy bubble cloud) throughout the procedure. In this specific example, the Histotripsy system (and therapy subsystem, including the transducer, drive electronics, and excitation sequence) would be further configured to have sufficient therapy head room to enable this use case. In this example, the system could be further configured to monitor / assess disturbances, heat, and / or any additional therapy considerations that may affect the desired therapy outcome (or performance measure / metric). There may also be specific user-guided workflow steps to ensure / minimize physical collisions with the probe at translated positions, and similarly, treatment patterns / paths (linear columns vs. bottom-up spirals of radiation) may be uniquely configured in non-obvious ways to accommodate this use case (e.g., verifying locked probe position at the most extreme planning location (bottom) to minimize collisions, etc.). Additionally, other features to assist with real or perceived differences between the plan and target tissue based on speed-of-sound differences in media (tissue and water) between the imaging probe and planning depth / location may be implemented to ensure the user has an accurate depiction of the treatment contour in space.

[0225]

[0231] Example 3

[0226]

[0232] In another representative example, including an embodiment with motorized probe translation and rotation, the imaging probe may be translated or "shortened" away from the maximum position per treatment requirements, with the translation tolerance determined based on user selection of the intended treatment plan size (of target and margin contours). In this example, the system is configured to provide the best possible image quality throughout the treatment and minimal real or perceived difference between the plan and target tissue. Thus, the system and system software may be configured with an automated set of rules for probe position in context to the user-selected plan.

[0227]

[0233] Example 4

[0228]

[0234] Based on the above, in this representative example, the system is configured to allow user (manual or motorized) probe translation and probe rotation, and after determining and locking the probe in the desired position / location, the system, directed via software control and user input, is configured to perform an automated, robotically-enabled imaging sweep of the patient. The robotically-enabled tracked imaging sweep can be programmed to include minimum / desired parameters such as speed or rate, distance, angularity or arc, other degree-of-freedom manipulation (roll, pitch, yaw, etc.), and / or any other sweep variables. The sweep can be viewed in replay through the system UI, edited and / or cropped to enrich the sweep data, and after these steps, can be directed to other reference data (CT, MRI, PET CT, contrast-enhanced imaging, etc.) through a registration process to generate 2D, 3D, and / or 4D models (including motion models).

[0229]

[0235] Example 5

[0230]

[0236] In another example, treatment head designs based on computer-aided design and surface models may be rendered (geometrically and scale-accurate) in a DICOM viewing tool to give the user the ability to select and simulate various treatment head variations in likely patients / cases to help evaluate interactions, collisions, treatment plan size, shape, location, acoustic paths / windows, acoustic field interactions, etc. The simulation software may also include the ability to virtually simulate imaging probe position and image quality using imaging simulator algorithms. This may be used in part to determine, by way of non-limiting example, preferred use configurations (examples above) and / or specific treatment head selection and treatment approaches, etc.

[0231]

[0237] Example 6

[0232]

[0238] In another example, during patient planning, the user translates the probe axially and then rotates it 90 degrees for optimal visualization of the target volume. As the user is guided through the various planning screens, the patient plan is locked, and the probe is then rotated back 90 degrees and then retracted distal to the home position. Treatment can begin once the robot detects the fully retracted probe home position, and the user can complete the associated UI screens.

[0233]

[0239] Example 7

[0234]

[0240] In another example, the therapy head needs to be attached to the robotic arm before use or during system setup / initialization. The therapy head, including the robotic arm coupler, may be attached to a quick connect plate, allowing the I / O cable to be easily aligned and inserted into the connection port of the quick connect adapter. If the therapy head needs to be replaced during or after a procedure, the I / O cable is removed and the therapy head is disconnected from the robotic arm. More specifically, the robotic arm coupler is disconnected from the quick connect plate before or after the I / O cable is removed from the quick connect adapter.

[0235] Usage environment

[0241] The disclosed systems, methods of use, and system usage may be performed in numerous environments and settings, with or without various support systems such as anesthesia, including, but not limited to, treatment suites, operating rooms, hybrid rooms, in-patient and out-patient settings, ambulatory settings, imaging centers, radiology, radiation therapy, oncology, surgery, and / or any medical center, as well as physician offices, mobile healthcare centers or systems, automobiles and related vehicles (e.g., vans), air and sea transport vehicles such as aircraft and ships, and / or any structure capable of providing temporary treatment support (e.g., tents). In some cases, the systems and / or subsystems disclosed herein may also be provided as integrated features into other environments, such as direct integration of the Histotripsy therapy subsystem into an MRI scanner or patient surface / bed, with at least the therapy generator and transducer integrated therein; in other cases, the Histotripsy configuration further includes a robotic positioning system that may be further integrated into a scanner or bed-centric design.

[0236] Concatenation

[0242] The system can 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 / histotripsy (e.g., providing an acoustic window and medium between the transducer and the patient, and its support). These can include different form factors of such, including open and closed device solutions, as well as several arrangements that can be configured to allow dynamic control over the acoustic medium (e.g., temperature, dissolved gas content, level of particulate filtration, sterility, volume, composition, etc.). Such dynamic control components may be integrated directly into the system (within the cart) or may be in temporary / intermittent or continuous communication with the system, but may be separate devices and / or external to the cart.

[0237]

[0243] The coupling subsystem typically comprises 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 interfaces to other surfaces or devices). In most embodiments, the coupling medium is water, and the water may be conditioned (e.g., chilled, degassed, filtered, etc.) before or during treatment. Various conditioning parameters may be employed based on the configuration of the system and its intended use / application.

[0238]

[0244] The reservoir or media container can be formed and shaped into various sizes and shapes to conform to the patient, allowing the therapy transducer to engage / access and work within the acoustic medium per defined and required working space (such as a minimum volume of media to allow the therapy transducer to be positioned and / or moved through one or more treatment positions or patterns and at various standoffs or depths from the patient), and the reservoir or media container can also mechanically support the load and load distribution through the use of mechanical and / or electromechanical support structures. Representative examples include support frames. The container may be of various shapes, sizes, curvatures, and dimensions and may include various material compositions (single, multiple, composite, etc.) that may vary throughout. In some embodiments, the container can include features such as insertable and removable films, drapes, membranes, blowers, etc. that can be used to conform to the patient and assist in containing / containing the media within the container. The container can further include various sensors (e.g., volume / fill level), drainage (e.g., inlet / outlet), lighting (e.g., LEDs), markings (e.g., fill lines, setup orientation, etc.), text (e.g., labeling), etc.

[0239]

[0245] In one embodiment, the reservoir or media container includes a sealable frame into which a membrane and / or film can be placed to provide a comfortable means of contacting the reservoir (which will later comprise the therapy head / therapy transducer) as an interface to the patient, further providing a barrier to the media (e.g., water) between the patient and the therapy transducer. In other embodiments, the membrane and / or film can include an opening whose patient-contacting edge provides a fluid / mechanical seal with the patient, but in contrast allows direct media communication with the patient (e.g., a direct degassed water interface with the patient). The reservoir or media container superstructure in both of these examples can further provide a proximal portion (e.g., top) of the structure that is open or enclosed (e.g., to prevent spillage or provide additional features).

[0240]

[0246] The disclosed membranes can include various elastomers, viscoelastic polymers, thermoplastics, thermoplastic elastomers, thermoset polymers, silicones, urethanes, rigid / flexible copolymers, block copolymers, random block copolymers, and the like. Materials can be hydrophilic, hydrophobic, surface-modified, coated, extracted, and the like, and can further contain various additives to enhance performance, appearance, or stability. In some embodiments, the thermoplastic elastomer can be styrene-ethylene-butylene-styrene (SEBS) or other similar strong, flexible elastomers. The membrane form factor can be flat or pre-shaped prior to use. In other embodiments, the membrane can be inelastic (i.e., convex) and pressed against the patient's skin to acoustically couple the transducer to the tissue. Systems and methods for controlling the level of contaminants (e.g., particulates, etc.) on the membrane to maintain an appropriate level of ultrasound coupling are also disclosed. Too many particulates or contaminants can cause ultrasound scattering. This can be achieved with a removable film or coating on the membrane's outer surface to protect against contamination.

[0241]

[0247] The materials may be formed into useful thin films through molding, casting, spraying, ultrasonic spraying, extrusion, and / or any other processing method that yields useful embodiments. The materials may be single-use or reposable / reusable. The materials may be non-sterile, aseptically clean, or sterile, and sterilization may include any known method, including but not limited to, ethylene oxide, gamma, e-beam, autoclaving, steam, hydrogen peroxide, plasma, chemicals, etc. The thin films may further comprise an outer molded or overmolded frame to provide mechanical stability to the thin film during handling, including assembly, setup, and disassembly of the coupling subsystem. Representatively, various parameters of the thin film may be optimized for this use, including thickness, thickness profile, density, formulation (e.g., polymer molecular weight and copolymer ratio, additives, plasticizers, etc.), specifically optimized to maximize acoustic transmission properties, including impact on cavitation onset threshold and / or minimizing ultrasound imaging artifacts, including but not limited to thin film reflections.

[0242]

[0248] The open reservoir or media container can include various methods of filling, including using pre-prepared media or water that can be delivered to the container, possibly to predefined specifications (levels of temperature, gas saturation, etc.), or can include additional features integrated into the design that allow for filling and draining (e.g., ports, valves, hoses, tubing, fittings, bags, pumps, etc.). These features may be further configured to interface into or to other devices, including, for example, the fluidics system. In some cases, the fluidics system can be an in-house media preparation system in a hospital or medical environment room, or conversely, a mobile cart-based system that can prepare and transport media from a cart to a media container, etc.

[0243]

[0249] The enclosed iterations of the reservoir or media container can include various features for sealing, in some embodiments, to the proximal / top portion or structure of the reservoir / container, or in other cases, the sealing can include sealing features on the transducer or transducer housing. Additionally, some embodiments can 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 for changes in focal distance to the target area without moving the transducer. Thus, integrated features enabling fluid communication and control thereof can be provided (the ability to provide / remove fluid on demand), including the ability to monitor and control various fluid parameters, some of which are disclosed above. To provide this functionality, the overall system, and as part of it, the coupling subsystem, can include a fluid regulation system, which can include various electromechanical devices, systems, power, sensing, computing, pumping, filtering, and control systems, etc. The reservoir can also be configured to receive signals that deform or change shape in a specific and controlled manner to allow the target point to be adjusted without moving the transducer.

[0244]

[0250] The articulated support system can include a variety of mechanical support devices for interfacing the reservoirs / containers and media 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 can have a proximal interface with one or more locations (and features) of the bed, including but not limited to a frame, rails, customized rails, or inserts, and one or more distal locations of the reservoirs or containers. The arm can also be a feature embodied on one or more carts, which can be configured in a variety of non-limiting permutations, and in some cases, the cart solely serves to support and provide the disclosed support structure.

[0245]

[0251] In some embodiments, the support structure and arm may be realized as a standalone cart or may be 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, interventional, surgical, or other type, and may further comprise various user input features for actuating / controlling the robot arm (e.g., disposed on / within the coupling medium) and / or coupling solution features (e.g., fill, drain, etc.). 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 placing a therapy transducer at a desired / known location and within the coupled support structure.

[0246]

[0252] Overall, significant unmet needs exist today in interventional and surgical medical procedures across various types of procedures, including procedures utilizing minimally invasive devices and approaches to treat disease and / or injury, and unmet needs may be solved with entirely new medical procedures. Today's medical system capabilities are often limited by access, such that a less invasive or non-invasive approach would be preferable, or today's tools lack the ability to deliver the desired / required tissue effect (e.g., working around / through critical structures without significant injury), or the physical setup of the system makes certain treatment approaches less desirable or possible, and combinations of approaches may enable entirely new procedures and approaches not possible today, along with enhanced tissue-affecting therapies.

[0247]

[0253] Additionally, there is a unique need to enable histotripsy delivery, including robotic histotripsy delivery, where one or more histotripsy therapy transducers may be configured to acoustically couple to the patient using a fully sealed approach (e.g., no acoustic medium communication with the patient's skin) and to allow the one or more histotripsy transducers to be moved within the coupling solution without impeding the movement / movement of the robotic arm or interfering / obstructing the coupling interface, which may affect the intended treatment and / or target location.

[0248]

[0254] By way of non-limiting example, disclosed herein are Histotripsy acoustic and patient coupling systems and methods for enabling Histotripsy therapy / treatment in any setting envisioned from an interventional suite, operating room, hybrid suite, imaging center, medical center, office environment, mobile treatment center, and / or other. The following disclosure further describes novel systems used to create, control, maintain, modify / enhance, monitor, and set up / tear down acoustic and patient coupling systems in a variety of approaches, methods, environments, architectures, and workflows. In general, the disclosed novel system can allow a coupling medium, in some instances degassed water, to be interfaced 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 treatment location (and volume), delivery can require physically moving the histotripsy therapy transducer within a defined workspace that includes the coupling medium, and the coupling system is configured to allow said movement of the therapy transducer (and positioning system, e.g., a robot) freely and unhindered by a coupling support system (e.g., a frame or manifold that holds the coupling medium).

[0249] Thin / Barrier Films and Related Architectures

[0255] The thin membranes and barrier films may be constructed from a variety of biocompatible materials capable of providing a conformal connection to the patient's anatomy with minimal or no trapped air bubbles that could interfere with ultrasound imaging and histotripsy therapy, and a sealed barrier layer between the patient's anatomy and the ultrasound medium contained within the working space provided by the frame and assembly.

[0250]

[0256] The membrane and barrier film materials may comprise flexible and elastic biocompatible materials / polymers, such as various thermoplastic and thermoset materials, as well as permanent or bioabsorbable polymers. Additionally, the UMC frame may comprise the same materials. In some cases, the membrane may be a pre-shaped or flat rigid or semi-rigid polymer. Some non-limiting examples of materials from which thin and barrier films can be made include, but are not limited to, polyurethanes, polystyrene copolymers, poly(lactic acid), poly(glycolic acid), poly(hydroxybutyric acid), poly(phosphazine), polyesters, polyethylene glycol, polyethylene oxide, polyacrylamide, polyhydroxyethyl acrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacetate, polycaprolactone, polyethylene, polypropylene, polybutylene, aliphatic polyesters, glycerin, poly(amino acids), copoly(ether esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyalkylene oxalates, polyoxaesters, polyorthoesters, polyphosphazenes, and copolymers, block copolymers, homopolymers, blends and combinations thereof. In some embodiments, the films are composed of polystyrene copolymers and block copolymers with ethylene, butadiene, butylene, and / or additional styrene blocks, with examples including styrene-butadiene-styrene (SBS) and styrene-ethylene-butylene-styrene (SEBS). In other examples, they may be composed of various silicones and silicone copolymers and / or formulations of various silicone constituents, including those with lower molecular weight silicones or silicone-based oils. These may further contain various additives, including additives to enhance thermal or optical stability, mechanical properties, biological properties (e.g., anti-infective properties), sterilization stability, including steam, heat, chemical, radiation, and / or e-beam stability, and oils or low molecular weight fluids to make the material moldable or flexible and / or improve adhesion to other surfaces (e.g., backings, skins, etc.).In some embodiments, the thin film / barrier film comprises 10-80% oil by weight, and in other embodiments, 40-60% oil. In some embodiments, the oil is paraffin oil. In some embodiments, the additives also include blooming agents and / or other agents to enhance surface properties. Some thin film / barrier film compositions may also include one or more components, such as an adhesive or adhesive formulation to enable adhesion of the thin film / film to the patient's anatomy (e.g., epidermis), and retarding features aimed at preventing the thin film from "fading" from the body and / or frame / manifold.

[0251]

[0257] The thin film / barrier film may vary in thickness from 0.01 mm to 7 mm, and in some embodiments, is preferably between 1 mm and 5 mm. In some embodiments, the thin film has a thickness between 2 mm and 4 mm, and in further embodiments, the thin film has a thickness between 2.5 mm and 3.5 mm. The thin film can have a tensile strength of >0.2 MPa. In some embodiments, the tensile strength can be between 0.4 MPa and 1 MPa. The thin film can be configured to stretch or elongate by up to 200%, and in some embodiments, up to 500% or up to 3000%. The thickness can be selected to balance physical-mechanical properties, impact on acoustic cavitation / histotripsy threshold, fit to the patient's anatomy, and the degree of thin film stretching and displacement (based on the setup location and expected ultrasound medium volume and relative spatial distribution). These may be transparent or translucent, and / or may be colored or dyed, including completely or partially colored or dyed, and as markings or continuous / discrete areas. In some examples, the membrane is preferably transparent / translucent to allow visibility of the workspace and any potential air bubbles present in the ultrasound medium and sealed system, as well as visualization of the ultrasound imaging probe mounted within the central bore of the therapy transducer. This may include, by way of example, viewing the probe and its position / orientation (e.g., when translated into the epidermis and / or retracted back again away from the epidermis).

[0252]

[0258] The thin film / barrier film may further include structural components such as a frame or fixture that can further improve the ease of handling and use of the acoustic and patient connection system, including, but not limited to, treatment setup and teardown, and without acoustic window size. The frame may be constructed from biocompatible metals and / or polymers, including, but not limited to, aluminum, aluminum alloy, acrylonitrile butadiene styrene (ABS), polyethylene, propylene, polyamide, and / or other impact-resistant materials. The disclosed frame may be positioned along the contour of the thin film / barrier film edge, which may be continuous or segmented / lengthwise. Typically, the frame is positioned along the contour of the outer edge of the thin film. The frame may be positioned within the thin film / barrier film (e.g., over a molded thin film), or conversely, constructed on the thin film / barrier film, with the frame molded around the thin film. Thus, the disclosed concepts can provide one or more means of interfacing to the thin film / barrier film, including "hard," "semi-hard," and / or "soft" interfaces, or combinations thereof. For example, creating a seal along exposed / visible soft membrane / barrier film surfaces and edge surfaces versus sealing and interfacing along a hard membrane frame to a larger system "frame and assembly" described below. Additionally, the interface may comprise various features to enhance mechanical joint, engagement, fit, interlock, and / or seal, including, but not limited to, mechanical ridges, grooves, pins, keys, and interlocking structures that may be provided with various heights, depths, grading / pitch, taper, angles, standoffs, shapes, spacing, frequency / quantity, and / or cutouts. In some examples, the membrane / barrier film may comprise a window for direct physical / acoustic access, and the edge region of the window (e.g., cutout) may be attached to the patient, with the edge region serving as a "mechanical support interface and frame-like feature."

[0253]

[0259] Thin film / barrier film frames may be made from a variety of shapes and dimensions / sizes to accommodate various workspaces and workspace volumes, as provided by the articulation system, and for transducers and associated required movement spaces from smaller (<5 cm) to larger (>20 cm in long axis) to accommodate location / poses, setups, and target anatomical locations (e.g., abdomen, nerve, etc.), where various acoustic windows and conformal anatomical contours (compatible with abdomen, thoracic cavity / thorax, head / neck, extremities, etc.) are desirable. Frames may be constructed from a variety of metals, alloys, polymers / plastics, ceramics, and / or composites and combinations thereof, and using casting, molding, machining, and / or any useful / known fabrication method. In some embodiments, aluminum is preferred. In other embodiments, they are injection-molded plastics from the list above.

[0254]

[0260] Overall, the physical, mechanical, chemical, dimensional, and process-induced properties / properties of the disclosed thin films provide the ability to control, and in some cases minimize, acoustic cavitation initiation (histotripsy) threshold requirements compared to other thin films. In some embodiments, thin films and barrier films can increase the cavitation threshold (and required drive amplitude) by 50% or more (over thresholds obtained directly through the epidermis and combined using degassed water). In other embodiments, by 10-50%, as similarly tested. In other embodiments, thin films / barrier films increase the threshold requirement by approximately 10%, and in preferred embodiments, they increase the threshold requirement by at most 5-10%. In some embodiments, they also provide this capability without reducing clinically relevant ultrasound imaging properties. In other embodiments, windows, as detailed above, may not provide a change in threshold in the case of direct acoustic access through the epidermis. This may include B-mode or other forms of ultrasound imaging, or post-acquisition image enhancement, some of which may be used to further enable multimodal image reconstruction, segmentation, registration and fusion (such as from forms of MRI, CT, cone-beam CT, fluoroscopy, and enhanced fluoroscopy).

[0255]

[0261] The therapeutic ultrasound systems described herein typically operate at a threshold voltage (to produce effective acoustic cavitation and histotripsy) that is as low as reasonably possible and capable of effective operation at maximum penetration depth.

[0256]

[0262] The use of thin films as described herein has advantages such as improved ease of use, enabling better targeting of difficult tissue locations in a patient, and improved patient comfort. Nevertheless, thin films have the disadvantage of placing an additional layer of material between the therapy transducer and the patient's epidermis. These additional layers—particularly thin films—have two potential effects: transmission loss and deviation.

[0257]

[0263] Transmission loss refers to how much of the ultrasound energy is coupled through the membrane—a function of thickness, sound speed, acoustic impedance, and the ability to achieve a bubble-free interface in the membrane and in any gel or oil layers used between the membrane and the tissue. The membrane addresses transmission effects by having an acoustic impedance close to that of water / tissue, while remaining thin enough that losses in the membrane itself are minimal. Contact is achieved through a combination of very high compliance that allows the membrane to conform to the body, the self-wetting nature of oil-infused materials, and application techniques (bubble swipes) that allow for control of the interface.

[0258]

[0264] Controlling the level of escape can be achieved by having similar sound speeds for the medium and the membrane, and by keeping the membrane as thin as possible. The level of escape is likely governed by the difference in sound speed between the connecting medium (e.g., water) and the tissue.

[0259]

[0265] The properties of the film that will affect the level of transmission loss and deviation are related to the properties of the raw materials (compositions and additives), the film design (e.g., film thickness, cross-section and surface roughness), the manufacturing process, and the method for deploying the film on the patient so that a sufficiently large and effective contact area is created.

[0260]

[0266] The raw materials for the thin film can be selected to have an acoustic impedance as close as possible to that of the ultrasound medium, and should be biocompatible and compatible with the ultrasound medium and any gels or oils used on the patient's epidermis. The thin film material can also provide sufficient temperature resistance (e.g., the use of antioxidants to enable the material to withstand high temperatures during the final manufacturing process) and environmental resistance during storage. The material should also be free of additives that could reduce ultrasound transmission (such as particulates that could scatter ultrasound). Other material properties that may offer advantages for the application include a high level of transparency (to allow visualization of air bubbles through the thin film), excellent puncture resistance (safety), avoidance of absorption of the ultrasound medium (e.g., water), and low bubble containment. Materials such as SEBS, which can leach / bloom mineral oil onto their surface, can improve the quality of contact between the thin film and any oils or gels used on the patient's epidermis (i.e., this should reduce the risk of trapped air bubbles). Nevertheless, the level of any leachable / bloomed material must be safe to handle and not contaminate the ultrasound medium.

[0261]

[0267] The membrane's mechanical properties and design must be specified to create a sufficiently large area of ​​effective ultrasonic coupling between the ultrasound transducer and the patient's epidermis. The area of ​​contact should not contain trapped air or air bubbles (which would cause transmission loss) and should not impose loads on the patient that could cause discomfort or injury or excessively change the position of internal organs. The membrane's cross-section in the patient contact area should be constant to avoid uneven transmission loss. The structural stiffness of the material should be low enough so that it remains taut while in contact with the patient's epidermis, preventing puckers, folds, or wrinkles in the epidermis, which could trap air. The preferred embodiment is a flat membrane that stretches during filling to become convex, providing an initial single point of contact with the patient. As the membrane is lowered or further expanded / filled, epidermal contact increases radially, broadly preventing the formation of trapped air pockets. Alternatively, a pre-shaped convex membrane may be used, but the risk is that this embodiment may not have sufficient material tension at the initial contact points or during the deployment phase.

[0262]

[0268] The manufacturing process also has an effect on the presence of air bubbles within the material, particulate and material contamination, material composition variations, film thickness variations, and surface roughness and imperfections, all of which can potentially increase transmission loss.

[0263] Frames and Assemblies

[0269] The interlocking solution frame and assembly, sometimes referred to as an ultrasound medium container (UMC), interlocking solution, and / or interlocking device, generally holds, seals, and supports the thin film / barrier film and is configured to enable / provide interfaces to: 1) the top enclosure (e.g., top enclosure / sealing), 2) fluid inlets / outlets (e.g., to receive / remove ultrasound medium), 3) mechanical arms, and 4) other features, including, but not limited to, membrane supports / constraints, handles, locking mechanisms (for membrane frame, enclosure, frame / assembly pieces), exhaust and bubble management, imaging probe control, etc. In some examples, the frame can incorporate a pressure sensor configured to measure the pressure of the medium within the UMC, which can be used to detect leaks or overpressure events. The UMC may further include a pressure relief valve.

[0264] ultrasonic medium

[0270] As previously mentioned, the ultrasound medium can comprise any applicable medium capable of providing sufficient and useful acoustic coupling to enable histotripsy treatment and sufficient clinical imaging (e.g., ultrasound). Ultrasound media can include, but are not limited to, various aqueous solutions / media, including mixtures with other cosolvent fluids, that may have favorable or more favorable acoustic qualities, including the ability to match the speed of sound, as part of the present disclosure and systems. Example media include degassed water and / or mixtures / cosolvents of degassed water with various alcohols, such as ethanol.

[0265] Mechanical Support Arm and Arm Architecture

[0271] Various designs and configurations of mechanical support arms (and arm architectures) can be employed to support the acoustic and patient connection system, including providing an efficient and ergonomic workflow for the user. Support arms can be configured with a range of degrees of freedom, including but not limited to, allowing for x, y, z, pitch, roll, and yaw, as well as additional interface features that may allow for additional height adjustment or translation.

[0266]

[0272] The arms can have various numbers and types of joints and segments. Typically, the arms have a minimum of two segments. In some configurations, the arms can have three to five segments.

[0267]

[0273] The arm is also configured to interface proximally with the main support base or base interface (e.g., robot, table, table / bed rail, cart, floor mount, etc.) and distally with the frame / assembly and overall "UMC" or "connected solution." This unique distal interface can further include features to control the position / orientation of the frame / assembly at the frame / assembly interface.

[0268]

[0274] For example, in some embodiments, the arm / frame interface may comprise a ball-joint 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 in interacting with the various wrists, which may include (by way of non-limiting example) additional handles or knobs to further enable positioning of the UMC / articulated solution. For example, a gimbal wrist may benefit from allowing the frame / assembly to have three degrees of freedom (independent of the arm degrees of freedom), including pitch, roll, and yaw adjustment.

[0269]

[0275] The support arm, further configured with an arm wrist interfaced with the frame / assembly, can include features such as brakes, including cable- or electronically-actuated brakes, and quick releases that can interact with one or more axes individually or in groups. The support arm can also include an electronic lift system and base support. In some embodiments, these lift systems / base supports are co-located with the robotic arm base, and the robotic arm is equipped with a histotripsy therapy transducer configured to fit / function within the enclosed articulated solution. In other embodiments, the support arm is placed on a separate cart. In some cases, the separate cart can include a fluidics 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-based structure / foundation capable of managing weight and tipping requirements.

[0270] Fluid Engineering Systems, Control Systems and System Architecture

[0276] As part of the overall fluidics management, the histotripsy system, including the acoustic / patient connection system, may be configured to include an automated fluidics system, primarily responsible for providing a reservoir for the preparation and use of the connection medium. The preparation may include the ability to degas, cool, monitor, regulate, supply / fill, and remove / drain the connection medium to and from the frame / assembly. The fluidics system may include an emergency high-flow system for rapid drainage of the connection medium from the UMC. In some embodiments, the fluidics system may be configured for single-use of the connection medium or alternatively for reuse of the medium. In some embodiments, the fluidics system may achieve positive air pressure or vacuum to perform leak testing of the UMC and membrane prior to filling the connection medium. Vacuum assistance may also be used to remove air from the UMC during the filling process. The fluidics system may further include a filter configured to prevent particulate contamination from reaching the UMC.

Claims

1. It is an ultrasonic treatment head, A therapeutic transducer array including an opening, A coupling assembly disposed within the opening of the therapeutic transducer array, further comprising one or more exhaust ports configured to receive an imaging probe and to expel air bubbles from the distal surface of the therapeutic transducer array and / or the coupling assembly when the treatment head is submerged in fluid, and An ultrasonic treatment head equipped with [unclear].

2. An ultrasonic treatment head according to claim 1, wherein the connecting assembly is formed in an overall cylindrical shape.

3. An ultrasonic treatment head according to claim 1, wherein the connecting assembly includes a distal portion configured to receive the imaging probe.

4. An ultrasonic treatment head according to claim 3, wherein the one or more exhaust holes are arranged in the distal portion.

5. An ultrasonic treatment head according to claim 1, wherein the one or more exhaust ports are selected from groups consisting of two, three, and four exhaust ports.

6. An ultrasonic treatment head according to claim 1, further comprising at least four exhaust ports, the four exhaust ports being arranged approximately 90 degrees apart around a hole in the coupling assembly configured to receive the imaging probe.

7. An ultrasonic treatment head according to claim 1, wherein one or more of the exhaust holes are configured to expel air bubbles from the distal surface, through the connecting assembly, and from the proximal portion of the connecting assembly.

8. An ultrasonic treatment head according to claim 7, further comprising one or more channels arranged along at least a portion of the longitudinal length of the connecting assembly.

9. An ultrasonic treatment head according to claim 8, wherein one or more channels are fluidly connected to one or more exhaust holes located in the distal portion of the connecting assembly.

10. An ultrasonic treatment head according to claim 9, wherein one or more channels are configured to direct the air bubbles into the cavity of the connecting assembly.

11. An ultrasonic treatment head according to claim 9, wherein one or more channels are configured to direct the air bubbles toward one or more exhaust holes located in the proximal portion of the connecting assembly.

12. An ultrasonic treatment head according to claim 9, wherein one or more channels are configured to direct the air bubbles toward one or more radiating openings along the radiating surface of the connecting assembly.

13. An ultrasonic treatment head according to claim 1, further comprising a connecting assembly and an exhaust assembly disposed within the distal portion of the connecting assembly.

14. An ultrasonic treatment head according to claim 13, wherein one or more exhaust holes are formed within the exhaust assembly.

15. An ultrasonic treatment head according to claim 13, wherein the exhaust assembly includes a hole configured to receive the imaging probe.

16. An ultrasonic treatment head according to claim 15, wherein the exhaust assembly comprises two halves that collectively form the holes.

17. An ultrasonic treatment head according to claim 13, wherein the exhaust assembly includes a concave distal surface.

18. An ultrasonic treatment head according to claim 13, wherein the exhaust assembly is in fluid communication with the inside of the connecting assembly.

19. An ultrasonic treatment head according to claim 18, wherein the connecting assembly includes a cavity located proximal to the exhaust assembly.

20. An ultrasonic treatment head according to claim 19, wherein the exhaust assembly is configured to direct air bubbles into the cavity from one or more exhaust holes.

21. An ultrasonic therapy head according to claim 1, wherein the connecting assembly is configured for axial translation relative to the therapeutic transducer array.

22. An ultrasonic treatment head according to claim 1, wherein the distal surface of the connecting assembly is angled or sloped inward toward the one or more exhaust holes.

23. An ultrasonic treatment head according to claim 14, wherein the distal surface of the exhaust assembly is angled or sloped inward toward the one or more exhaust holes.

24. An ultrasonic treatment head according to claim 1, wherein the connecting assembly is made of a material that exhibits zero expansion.

25. An ultrasonic treatment head according to claim 24, wherein the zero-expansion material is made of aluminum.

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