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WO2025038127A1 - Systèmes de couplage ultrasonore pour histotripsie et systèmes, procédés et dispositifs associés - Google Patents

Systèmes de couplage ultrasonore pour histotripsie et systèmes, procédés et dispositifs associés Download PDF

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Publication number
WO2025038127A1
WO2025038127A1 PCT/US2023/083452 US2023083452W WO2025038127A1 WO 2025038127 A1 WO2025038127 A1 WO 2025038127A1 US 2023083452 W US2023083452 W US 2023083452W WO 2025038127 A1 WO2025038127 A1 WO 2025038127A1
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WO
WIPO (PCT)
Prior art keywords
frame body
ultrasound
medium container
coupling
upper frame
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PCT/US2023/083452
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English (en)
Inventor
Justin S. Grumbir
Jon D. Schell
Franklin J. BURQUEST
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Histosonics Inc
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Histosonics Inc
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Publication of WO2025038127A1 publication Critical patent/WO2025038127A1/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B34/00—Computer-aided surgery; Manipulators or robots specially adapted for use in surgery
    • A61B34/30—Surgical robots
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/22—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/225—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/22—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/225—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
    • A61B17/2251—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient
    • A61B2017/2253—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient using a coupling gel or liquid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N7/02—Localised ultrasound hyperthermia

Definitions

  • the present disclosure details novel high intensity therapeutic ultrasound (HITU) systems configured to produce acoustic cavitation, methods, devices and procedures for the minimally and non-invasive treatment of healthy, diseased and/or injured tissue.
  • HITU high intensity therapeutic ultrasound
  • the acoustic cavitation systems and methods described herein, also referred to Histotripsy may include transducers, drive electronics, positioning robotics, imaging systems, coupling systems, and integrated treatment planning and control software to provide comprehensive treatment and therapy for soft tissues in a patient.
  • Histotripsy or pulsed ultrasound cavitation therapy, is a technology where extremely short, intense bursts of acoustic energy induce controlled cavitation (microbubble formation) within the focal volume. The vigorous expansion and collapse of these microbubbles mechanically homogenizes cells and tissue structures within the focal volume. This is a very different end result than the coagulative necrosis characteristic of thermal ablation.
  • Histotripsy Compared with conventional focused ultrasound technologies, Histotripsy has important advantages: 1) the destructive process at the focus is mechanical, not thermal; 2) cavitation appears bright on ultrasound imaging thereby confirming correct targeting and localization of treatment; 3) treated tissue generally, but not always, appears darker (more hypoechoic) on ultrasound imaging, so that the operator knows what has been treated; and 4) Histotripsy produces lesions in a controlled and precise manner. It is important to emphasize that unlike thermal ablative technologies such as microwave, radiofrequency, high-intensity focused ultrasound (HIFU), cryo, or radiation, Histotripsy relies on the mechanical action of cavitation for tissue destruction and not on heat, cold or ionizing energy.
  • thermal ablative technologies such as microwave, radiofrequency, high-intensity focused ultrasound (HIFU), cryo, or radiation
  • the present disclosure is directed to histotripsy and the various systems, methods, and devices associated therewith, and more particularly to coupling systems or subsystems (used interchangeably throughout) suitable for use with histotripsy and the various systems, methods and devices associated therewith
  • the present disclosure describes coupling systems or subsystems including an ultrasound medium container or reservoir for histotripsy.
  • the container or reservoir may include a frame body, a coupling membrane, and at least one of a plurality of constraint connectors or a frame support bracket, or both.
  • the frame body includes an upper frame body portion defining an upper frame cavity and a lower frame body portion defining a lower opening.
  • the coupling membrane is connected in part to the lower frame body portion and extends across the lower frame opening.
  • the coupling membrane seals the upper frame cavity and/or the lower frame opening.
  • the constraint connectors are positioned intermittently around an exterior of the frame body. The constraint connectors being configured to releasably secure a constraint member to the frame body.
  • the plurality of constraint connectors may extend upwardly and outwardly from the lower frame body portion.
  • the upper frame body portion may include an upper frame sidewall extending between a sidewall upper edge and a sidewall lower edge, an interior of the upper frame sidewall defining the upper frame cavity.
  • a perimeter of the sidewall upper edge may be larger than a perimeter of the sidewall lower edge forming an upper frame body defining a truncated cone shape.
  • the upper frame body portion may include a pier configured to connect the ultrasound medium container to a mechanical support arm.
  • the pier defines a shaped body extending outwardly from an exterior of the upper frame body portion.
  • the frame body may further include one or more frame clamps configured to lock the lower frame body portion to the upper frame body portion.
  • Each clamp may include a clamp base secured to the exterior of the upper frame body portion, a clamp latch secured to the exterior of the lower frame body portion, a clamp handle pivotably connected to the clamp base, and a connecting rod connecting the clamp handle to the clamp latch.
  • the frame clamp being configured to transition between a locked and unlocked position.
  • the one or more frame clamps are adjustable frame clamps configured to adjust a gap distance between the upper and lower frame.
  • the gap distance may be adjusted to accommodate membranes of various thicknesses.
  • the container or reservoir may include a frame support bracket configured to connect the frame body to a mechanical support arm in a manner which stabilizes the position of the ultrasound medium container or reservoir.
  • the container or reservoir may be stabilized by the support bracket in a position relative to a patient.
  • the frame support bracket may include a central bracket portion and one or more support wings extending from the central bracket portion, wherein the one or more support wings follow an outer perimeter of the upper frame body.
  • An outer ledge of the upper frame body portion may sit on top of the one or more wings.
  • the central bracket portion may include two or more inner tabs extending inwardly from an inner surface thereof.
  • the two or more inner tabs being spaced apart to define a tab cavity therebetween and an inner cavity ledge on top of the tab cavity.
  • the inner tabs, tab cavity, and the inner cavity ledge of the central bracket portion being configured to matingly engage the pier of the upper frame body portion.
  • the central bracket portion may also include one or more outer tabs extending outwardly from an outer surface thereof.
  • the one or more outer tabs configured to matingly engage a separate mechanical support arm.
  • the one or more support wings may include a first and second support wings.
  • the first support wing may extend circumferentially around the upper frame body portion from a first side of the central bracket portion.
  • the first support wing may extend between a first fixed end portion and a first free end portion with a first central wing portion positioned therebetween.
  • the first central wing portion may be thinner than at least one of the first fixed end portion, the first free end portion, or both.
  • the second support wing may extend circumferentially around the upper frame body portion from a second opposite side of the central bracket portion.
  • the second support wing may extend between a second fixed end portion and a second free end portion with a second central wing portion positioned therebetween.
  • the second central wing portion may be thinner than at least one of the second fixed end portion, the second free end portion, or both.
  • the present disclosure also describes an ultrasound therapy system including at least a coupling assembly, an ultrasound therapy transducer, and a robotic positioning arm.
  • the ultrasound therapy transducer being configured to provide ultrasound therapy when at least partially submerged within the acoustic coupling medium of the ultrasound medium container.
  • the robotic positioning arm being coupled to the ultrasound therapy transducer.
  • the robotic positioning arm being configured to move the ultrasound therapy transducer within the ultrasound medium container relative to the patient while maintaining acoustic coupling with the patient via the acoustic coupling medium.
  • the coupling assembly may include an ultrasound medium container, an acoustic coupling medium, and a constraint member.
  • the constraint member may include pores.
  • the ultrasound medium container may include a frame body sealed with a coupling membrane and defining a frame cavity configured to receive the coupling medium therein.
  • a plurality of constraint connectors may extend from an exterior of the frame body to attach the constraint member to the frame body, and particularly via the pores.
  • the frame body may also include a frame support bracket attached to an exterior surface of the frame body, the frame support bracket configured to stabilize a position of the ultrasound medium container relative to a patient when secured to a mechanical support arm.
  • the methods include, in no particular order, positioning an ultrasound medium container configured to receive an acoustic coupling medium over a patient, locking the ultrasound medium container into a position, adding the acoustic coupling medium to the container, and introducing the ultrasound therapy introducer into the container or medium.
  • the methods of acoustically coupling an ultrasound treatment system to a patient prior to treatment include positioning an ultrasound medium container configured to receive an acoustic coupling medium over a patient, wherein the ultrasound medium container includes a frame body including an upper frame body portion defining an upper frame cavity and a lower frame body portion defining a lower frame opening.
  • the coupling membrane connected in part to the lower frame body portion and extending across the lower frame opening. The coupling membrane seals the upper frame cavity and/or the lower frame opening.
  • the ultrasound medium container may further include at least one of a plurality of constraint connectors extending from an exterior surface of the frame body, a frame support bracket secured to the exterior surface of the frame body, or both.
  • the methods of acoustically coupling an ultrasound treatment system to a patient prior to treatment include locking the ultrasound medium container into a position relative to a patient for optimal acoustic coupling, [0024] In some embodiments, the methods of acoustically coupling an ultrasound treatment system to a patient prior to treatment include adding the acoustic coupling medium to the ultrasound medium container in sufficient amount to submerge an ultrasound therapy transducer therein and cause the coupling membrane into contact with a portion of the patient’s skin.
  • the methods of acoustically coupling an ultrasound treatment system to a patient prior to treatment include introducing the ultrasound therapy introducer into the medium to form an acoustic coupling therebetween.
  • FIGS. 1 A-1B illustrate an ultrasound imaging and therapy system.
  • FIG. 2 is at least one embodiment of a histotripsy therapy and imaging system with a coupling system.
  • FIG. 3 A is a side view of a coupling assembly as described in at least one embodiment
  • FIGS. 3B-3D include a perspective view, side view, and bottom view, respectively, of an upper frame body of the coupling assembly of FIG. 3 A as described in at least one embodiment.
  • FIGS. 3E-3G include a perspective view, top view, and cross-sectional side view, respectively, of a lower frame body of the coupling assembly of FIG. 3 A as described in at least one embodiment;
  • FIGS. 4A-4E are each a side view of one or more constraint connectors of at least one embodiment;
  • FIGS. 5A-5B are each a side view of a frame clamp in an open and closed configuration as described in at least one embodiment;
  • FIG. 6 is a side view of a coupling assembly as described in at least one embodiment
  • FIGS. 7A-7C include a perspective view, top view, and side view, respectively, of a frame support bracket as described in at least one embodiment.
  • FIGS. 8A-8C include a perspective view, side view, and bottom view, respectively, of an upper frame body including the frame support bracket of FIGS. 7A-7C as described in at least one embodiment.
  • FIG. 9A is a side perspective view of a coupling assembly including a frame support bracket in an upright configuration as described in at least one embodiment
  • FIGS. 9B and 9C are each a side perspective view of an upper frame including a support bracket in an inverted configuration as described in at least one embodiment
  • FIGS. 10 A- 10C illustrate some embodiments of a membrane constraint
  • FIG. 11 is a perspective view of a coupling assembly including a membrane constraint as described in at least one embodiment.
  • the present disclosure is directed to histotripsy and the various systems, methods, and devices associated therewith, and more particularly to coupling systems or subsystems (used interchangeably throughout) suitable for use with histotripsy and the various systems, methods and devices associated therewith.
  • the histotripsy systems, methods and devices of the disclosure may be used for open surgical, minimally invasive surgical (laparoscopic and percutaneous), robotic surgical (integrated into a robotically-enabled medical system), endoscopic or completely transdermal extracorporeal non-invasive acoustic cavitation for the treatment of healthy, diseased and/or injured tissue including but not limited to tissue destruction, cutting, skeletonizing and ablation.
  • histotripsy may be used to create a cytoskeleton that allows for subsequent tissue regeneration either de novo or through the application of stem cells and other adjuvants.
  • histotripsy can be used to cause the release of delivered agents such as chemotherapy and immunotherapy by locally causing the release of these agents by the application of acoustic energy to the targets.
  • the acoustic cavitation system may include various sub-systems, including a Cart, Therapy, Integrated Imaging, Robotics, Coupling, and Software.
  • the histotripsy system also may comprise various Other Components, Ancillaries, 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, etc. All systems, methods, devices, systems (or subsystems), and means creating/controlling/delivering histotripsy are considered to be a part of this disclosure, including new related inventions disclosed herein.
  • FIG. 1 A generally illustrates histotripsy system 100 according to the present disclosure, comprising one or more devices or sub-systems described herein, such as, a therapy transducer 102, an imaging system 104, a display and control panel 106, a robotic positioning arm 108, and a cart 110.
  • the devices and sub-systems in various combinations may be configured to perform the various methods of histotripsy also provided herein.
  • the system can further include an ultrasound coupling interface and a source of coupling medium (FIG. 2).
  • FIG. IB is a bottom view of the therapy transducer 102 and the imaging system 104. As shown, the imaging system 104 can be positioned in the center of the therapy transducer 102.
  • imaging system 104 can include the imaging system positioned in other locations within the therapy transducer, or even directly integrated into the therapy transducer.
  • the imaging system 104 is configured to produce real-time imaging at a focal point of the therapy transducer 102.
  • the system also allows for multiple imaging transducers to be located within the therapy transducer to provide multiple views of the target tissue simultaneously and to integrate these images into a single 3-D image.
  • the histotripsy system may comprise one or more of various sub-systems, including a Therapy sub-system that can create, apply, focus and deliver acoustic cavitation/histotripsy through one or more therapy transducers, Integrated Imaging sub-system (or connectivity to) allowing real-time visualization of the treatment site and histotripsy effect through-out the procedure, a Robotics positioning sub-system to mechanically and/or electronically steer the therapy transducer, further enabled to connect/ support or interact with a Coupling sub-system to allow acoustic coupling between the therapy transducer and the patient, and Software to communicate, control and interface with the system and computer-based control systems (and other external systems) and various Other Components, Ancillaries and Accessories, including one or more user interfaces and displays, and related guided work-flows, all working in part or together.
  • a Therapy sub-system that can create, apply, focus and deliver acoustic cavitation/histotripsy through one or more therapy transducers
  • the system may further comprise various fluidics and fluid management components, including but not limited to, pumps, valve and flow controls, temperature and degassing controls, and irrigation and aspiration capabilities, as well as providing and storing fluids. It may also contain various power supplies and protectors.
  • the histotripsy system may include integrated imaging.
  • the histotripsy system can be configured to interface with separate imaging systems, such as C-arm, fluoroscope, cone beam CT, MRI, etc., to provide realtime imaging during histotripsy therapy.
  • the histotripsy system can be sized and configured to fit within a C-arm, fluoroscope, cone beam CT, MRI, etc.
  • the Cart 110 may be generally configured in a variety of ways and form factors based on the specific uses and procedures. In some cases, systems may comprise multiple Carts, configured with similar or different arrangements. In some embodiments, the cart may be configured and arranged to be used in a radiology environment and in some cases in concert with imaging (e.g., CT, cone beam CT and/or MRI scanning). In other embodiments, it may be arranged for use in an operating room and a sterile environment for open surgical or laparoscopic surgical and endoscopic application, or in a robotically enabled operating room, and used alone, or as part of a surgical robotics procedure wherein a surgical robot conducts specific tasks before, during or after use of the system and delivery of acoustic cavitation/histotripsy.
  • imaging e.g., CT, cone beam CT and/or MRI scanning
  • it may be arranged for use in an operating room and a sterile environment for open surgical or laparoscopic surgical and endoscopic application, or in a robotically enabled operating room, and used alone,
  • the cart may be positioned to provide sufficient work-space and access to various anatomical locations on the patient (e.g., torso, abdomen, flank, head and neck, etc.), as well as providing work-space for other systems (e.g., anesthesia cart, laparoscopic tower, surgical robot, endoscope tower, etc.).
  • anesthesia cart e.g., laparoscopic tower, surgical robot, endoscope tower, etc.
  • the Cart may also work with a patient surface (e.g., table or bed) to allow the patient to be presented and repositioned in a plethora of positions, angles and orientations, including allowing changes to such to be made pre, peri and post-procedurally.
  • a patient surface e.g., table or bed
  • It may further comprise the ability to interface and communicate with one or more external imaging or image data management and communication systems, not limited to ultrasound, CT, fluoroscopy, cone beam CT, PET, PET/CT, MRI, optical, ultrasound, and image fusion and or image flow, of one or more modalities, to support the procedures and/or environments of use, including physical/mechanical interoperability (e.g., compatible within cone beam CT work-space for collecting imaging data pre, peri and/or post histotripsy) and to provide access to and display of patient medical data including but not limited to laboratory and historical medical record data.
  • one or more Carts may be configured to work together.
  • one Cart may comprise a bedside mobile Cart equipped with one or more Robotic arms enabled with a Therapy transducer, and Therapy generator/amplifier, etc., while a companion cart working in concert and at a distance of the patient may comprise Integrated Imaging and a console/display for controlling the Robotic and Therapy facets, analogous to a surgical robot and master/slave configurations.
  • the system may comprise a plurality of Carts, all slave to one master Cart, equipped to conduct acoustic cavitation procedures.
  • one Cart configuration may allow for storage of specific sub-systems at a distance reducing operating room clutter, while another in concert Cart may comprise essentially bedside sub-systems and componentry (e.g., delivery system and therapy).
  • Histotripsy comprises short, high amplitude, focused ultrasound pulses to generate a dense, energetic, “bubble cloud”, capable of the targeted fractionation and destruction of tissue. Histotripsy is capable of creating controlled tissue erosion when directed at a tissue interface, including tissue/fluid interfaces, as well as well-demarcated tissue fractionation and destruction, at sub-cellular levels, when it is targeted at bulk tissue. Unlike other forms of ablation, including thermal and radiation-based modalities, histotripsy does not rely on heat cold or ionizing (high) energy to treat tissue. Instead, histotripsy uses acoustic cavitation generated at the focus to mechanically effect tissue structure, and in some cases liquefy, suspend, solubilize and/or destruct tissue into sub-cellular components.
  • Histotripsy can be applied in various forms, including: 1) Intrinsic-Threshold Histotripsy: Delivers pulses with a 1-2 cycles of high amplitude negative/tensile phase pressure exceeding the intrinsic threshold to generate cavitation in the medium (e.g., -24-28 MPa for water-based soft tissue), 2) Shock-Scattering Histotripsy: Delivers typically pulses 3-20 cycles in duration.
  • the shockwave (positive/compressive phase) scattered from an initial individual microbubble generated forms inverted shockwave, which constructively interfere with the incoming negative/tensile phase to form high amplitude negative/rarefactional phase exceeding the intrinsic threshold. In this way, a cluster of cavitation microbubbles is generated.
  • Boiling Histotripsy Employs pulses roughly 1-20 ms in duration. Absorption of the shocked pulse rapidly heats the medium, thereby reducing the threshold for intrinsic nuclei. Once this intrinsic threshold coincides with the peak negative pressure of the incident wave, boiling bubbles form at the focus.
  • the large pressure generated at the focus causes a cloud of acoustic cavitation bubbles to form above certain thresholds, which creates localized stress and strain in the tissue and mechanical breakdown without significant heat deposition.
  • At pressure levels where cavitation is not generated minimal effect is observed on the tissue at the focus. This cavitation effect is observed only at pressure levels significantly greater than those which define the inertial cavitation threshold in water for similar pulse durations, on the order of 10 to 30 MPa peak negative pressure.
  • Histotripsy may be performed in multiple ways and under different parameters. It may be performed totally non-invasively by acoustically coupling a focused ultrasound transducer over the skin of a patient and transmitting acoustic pulses transcutaneously through overlying (and intervening) tissue to the focal zone (treatment zone and site).
  • the application of histotripsy is not limited to a transdermal approach but can be applied through any means that allows contact of the transducer with tissue including open surgical laparoscopic surgical, percutaneous and robotically mediated surgical procedures.
  • the bubble clouds generated by histotripsy may be visible as highly dynamic, echogenic regions on, for example, B Mode ultrasound images, allowing continuous visualization through its use (and related procedures).
  • the treated and fractionated tissue shows a dynamic change in echogenicity (typically a reduction), which can be used to evaluate, plan, observe and monitor treatment.
  • This threshold can be in the range of 26 - 30 MPa for soft tissues with high water content, such as tissues in the human body.
  • the spatial extent of the lesion may be well-defined and more predictable.
  • peak negative pressures (P-) not significantly higher than this threshold, sub -wavelength reproducible lesions as small as half of the -6dB beam width of a transducer may be generated.
  • P- peak negative pressures
  • high-frequency pulses are more susceptible to attenuation and aberration, rendering problematical treatments at a larger penetration depth (e.g., ablation deep in the body) or through a highly aberrative medium (e.g., transcranial procedures, or procedures in which the pulses are transmitted through bone(s)).
  • Histotripsy may further also be applied as a low-frequency “pump” pulse (typically ⁇ 2 cycles and having a frequency between 100 kHz and 1 MHz) can be applied together with a high-frequency “probe” pulse (typically ⁇ 2 cycles and having a frequency greater than 2 MHz, or ranging between 2 MHz and 10 MHz) wherein the peak negative pressures of the low and high-frequency pulses constructively interfere to exceed the intrinsic threshold in the target tissue or medium.
  • the low-frequency pulse which is more resistant to attenuation and aberration, can raise the peak negative pressure P- level for a region of interest (RO I), while the high-frequency pulse, which provides more precision, can pin-point a targeted location within the ROI and raise the peak negative pressure P- above the intrinsic threshold.
  • This approach may be referred to as “dual frequency”, “dual beam histotripsy” or “parametric histotripsy.”
  • Additional systems, methods and parameters to deliver optimized histotripsy, using shock scattering, intrinsic threshold, and various parameters enabling frequency compounding and bubble manipulation, are herein included as part of the system and methods disclosed herein, including additional means of controlling said histotripsy effect as pertains to steering and positioning the focus, and concurrently managing tissue effects (e.g., prefocal thermal collateral damage) at the treatment site or within intervening tissue.
  • tissue effects e.g., prefocal thermal collateral damage
  • the various systems and methods which may include a plurality of parameters, such as but not limited to, frequency, operating frequency, center frequency, pulse repetition frequency, pulses, bursts, number of pulses, cycles, length of pulses, amplitude of pulses, pulse period, delays, burst repetition frequency, sets of the former, loops of multiple sets, loops of multiple and/or different sets, sets of loops, and various combinations or permutations of, etc., are included as a part of this disclosure, including future envisioned embodiments of such.
  • parameters such as but not limited to, frequency, operating frequency, center frequency, pulse repetition frequency, pulses, bursts, number of pulses, cycles, length of pulses, amplitude of pulses, pulse period, delays, burst repetition frequency, sets of the former, loops of multiple sets, loops of multiple and/or different sets, sets of loops, and various combinations or permutations of, etc.
  • the Therapy sub-system may work with other sub-systems to create, optimize, deliver, visualize, monitor and control acoustic cavitation, also referred to herein and in following as “histotripsy”, and its derivatives of, including boiling histotripsy and other thermal high frequency ultrasound approaches. It is noted that the disclosed inventions may also further benefit other acoustic therapies that do not comprise a cavitation, mechanical or histotripsy component.
  • the therapy sub-system can include, among other features, an ultrasound therapy transducer and a pulse generator system configured to deliver ultrasound pulses into tissue.
  • the therapy sub-system may also comprise components, including but not limited to, one or more function generators, amplifiers, therapy transducers and power supplies.
  • the therapy transducer can comprise a single element or multiple elements configured to be excited with high amplitude electric pulses (>1000V or any other voltage that can cause harm to living organisms).
  • the amplitude necessary to drive the therapy transducers for Histotripsy vary depending on the design of the transducer and the materials used (e.g., solid or polymer/piezoelectric composite including ceramic or single crystal) and the transducer center frequency which is directly proportional to the thickness of the piezo-electric material.
  • the transducer elements are formed using a piezoelectric-polymer composite material or a solid piezoelectric material. Further, the piezoelectric material can be of polycrystalline/ceramic or single crystalline formulation. In some embodiments the transducer elements can be formed using silicon using MEMs technology, including CMUT and PMUT designs.
  • the function generator may comprise a field programmable gate array (FPGA) or other suitable function generator.
  • the FPGA may be configured with parameters disclosed previously herein, including but not limited to frequency, pulse repetition frequency, bursts, burst numbers, where bursts may comprise pulses, numbers of pulses, length of pulses, pulse period, delays, burst repetition frequency or period, where sets of bursts may comprise a parameter set, where loop sets may comprise various parameter sets, with or without delays, or varied delays, where multiple loop sets may be repeated and/or new loop sets introduced, of varied time delay and independently controlled, and of various combinations and permutations of such, overall and throughout.
  • the generator or amplifier may be configured to be a universal single-cycle or multi-cycle pulse generator, and to support driving via Class D or inductive driving, as well as across all envisioned clinical applications, use environments, also discussed in part later in this disclosure.
  • the class D or inductive current driver may be configured to comprise transformer and/or auto-transformer driving circuits to further provide step up/down components, and in some cases, to preferably allow a step up in the amplitude.
  • They may also comprise specific protective features, to further support the system, and provide capability to protect other parts of the system (e.g., therapy transducer and/or amplifier circuit components) and/or the user, from various hazards, including but not limited to, electrical safety hazards, which may potentially lead to use environment, system and therapy system, and user harms, damage or issues.
  • specific protective features to further support the system, and provide capability to protect other parts of the system (e.g., therapy transducer and/or amplifier circuit components) and/or the user, from various hazards, including but not limited to, electrical safety hazards, which may potentially lead to use environment, system and therapy system, and user harms, damage or issues.
  • Disclosed generators may allow and support the ability of the system to select, vary and control various parameters (through enabled software tools), including, but not limited to those previously disclosed, as well as the ability to start/stop therapy, set and read voltage level, pulse and/or burst repetition frequency, number of cycles, duty ratio, channel enabled and delay, etc., modulate pulse amplitude on a fast time-scale independent of a high voltage supply, and/or other service, diagnostic or treatment features.
  • the Therapy sub-system and/or components of, such as the amplifier may comprise further integrated computer processing capability and may be networked, connected, accessed, and/or be removable/portable, modular, and/or exchangeable between systems, and/or driven/commanded from/by other systems, or in various combinations.
  • Other systems may include other acoustic cavitation/histotripsy, HIFU, HITU, radiation therapy, radiofrequency, microwave, and cryoablation systems, navigation and localization systems, open surgical, laparoscopic, single incision/single port, endoscopic and non-invasive surgical robots, laparoscopic or surgical towers comprising other energy-based or vision systems, surgical system racks or booms, imaging carts, etc.
  • one or more amplifiers may comprise a Class D amplifier and related drive circuitry including matching network components.
  • the matching network components e.g., an LC circuit made of an inductor LI in series and the capacitor Cl in parallel
  • the combined impedance can be aggressively set low in order to have high amplitude electric waveform necessary to drive the transducer element.
  • the maximum amplitude that Class D amplifiers is dependent on the circuit components used, including the driving MOSFET/IGBT transistors, matching network components or inductor, and transformer or autotransformer, and of which may be typically in the low kV (e.g., 1-3 kV) range.
  • Therapy transducer element(s) are excited with an electrical waveform with an amplitude (voltage) to produce a pressure output sufficient for Histotripsy therapy.
  • the excitation electric field can be defined as the necessary waveform voltage per thickness of the piezoelectric element. For example, because a piezoelectric element operating at 1 MHz transducer is half the thickness of an equivalent 500 kHz element, it will require half the voltage to achieve the same electric field and surface pressure.
  • the Therapy sub-system may also comprise therapy transducers of various designs and working parameters, supporting use in various procedures (and procedure settings).
  • Systems may be configured with one or more therapy transducers, that may be further interchangeable, and work with various aspects of the system in similar or different ways (e.g., may interface to a robotic arm using a common interface and exchange feature, or conversely, may adapt to work differently with application specific imaging probes, where different imaging probes may interface and integrate with a therapy transducer in specifically different ways).
  • Therapy transducers may be configured of various parameters that may include size, shape (e.g., rectangular or round; anatomically curved housings, etc.), geometry, focal length, number of elements, size of elements, distribution of elements (e.g., number of rings, size of rings for annular patterned transducers), frequency, enabling electronic beam steering, etc.
  • Transducers may be composed of various materials (e.g., piezoelectric, silicon, etc.), form factors and types (e.g., machined elements, chip-based, etc.) and/or by various methods of fabrication of.
  • Transducers may 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 tissue), and affording a breadth of working ranges, including relatively shallow and superficial targets (e.g., thyroid or breast nodules), versus, deeper or harder to reach targets, such as central liver or brain tumors.
  • desired outcomes e.g., acoustic cavitation/histotripsy without thermal injury to intervening tissue
  • relatively shallow and superficial targets e.g., thyroid or breast nodules
  • targets e.g., thyroid or breast nodules
  • the transducer may also be designed to allow for the activation of a drug payload either deposited in tissue through various means including injection, placement or delivery in micelle or nanostructures.
  • the disclosed system may comprise various imaging modalities to allow users to visualize, monitor and collect/use feedback of the patient’s anatomy, related regions of interest and treatment/procedure sites, as well as surrounding and intervening tissues to assess, plan and conduct procedures, and adjust treatment parameters as needed.
  • Imaging modalities may comprise various ultrasound, x-ray, CT, MRI, PET, fluoroscopy, optical, contrast or agent enhanced versions, and/or various combinations of. It is further disclosed that various image processing and characterization technologies may also be utilized to afford enhanced visualization and user decision making. These may be selected or commanded manually by the user or in an automated fashion by the system.
  • the system may be configured to allow side by side, toggling, overlays, 3D reconstruction, segmentation, registration, multi-modal image fusion, image flow, and/or any methodology affording the user to identify, define and inform various aspects of using imaging during the procedure, as displayed in the various system user interfaces and displays.
  • Examples may include locating, displaying and characterizing regions of interest, organ systems, potential treatment sites within, with on and/or surrounding organs or tissues, identifying critical structures such as ducts, vessels, nerves, ureters, fissures, capsules, tumors, tissue trauma/injury/disease, other organs, connective tissues, etc., and/or in context to one another, of one or more (e.g., tumor draining lymphatics or vasculature; or tumor proximity to organ capsule or underlying other organ), as unlimited examples.
  • Systems may be configured to include onboard integrated imaging hardware, software, sensors, probes and wetware, and/or may be configured to communicate and interface with external imaging and image processing systems.
  • the aforementioned components may be also integrated into the system’s Therapy sub-system components wherein probes, imaging arrays, or the like, and electrically, mechanically or electromechanically integrated into therapy transducers. This may afford, in part, the ability to have geometrically aligned imaging and therapy, with the therapy directly within the field of view, and in some cases in line, with imaging.
  • this integration may comprise a fixed orientation of the imaging capability (e.g., imaging probe) in context to the therapy transducer.
  • the imaging solution may be able to move or adjust its position, including modifying angle, extension (e.g., distance from therapy transducer or patient), rotation (e.g., imaging plane in example of an ultrasound probe) and/or other parameters, including moving/adjusting dynamically while actively imaging.
  • the imaging component or probe may be encoded so its orientation and position relative to another aspect of the system, such as the therapy transducer, and/or robotically-enabled positioning component may be determined.
  • the system may comprise onboard ultrasound, further configured to allow users to visualize, monitor and receive feedback for procedure sites through the system displays and software, including allowing ultrasound imaging and characterization (and various forms of), ultrasound guided planning and ultrasound guided treatment, all in real-time.
  • the system may be configured to allow users to manually, semi-automated or in fully automated means image the patient (e.g., by hand or using a robotically-enabled imager).
  • imaging feedback and monitoring can include monitoring changes in: backscatter from bubble clouds; speckle reduction in backscatter; backscatter speckle statistics; mechanical properties of tissue (i.e., elastography); tissue perfusion (i.e., ultrasound contrast); shear wave propagation; acoustic emissions, electrical impedance tomography, and/or various combinations of, including as displayed or integrated with other forms of imaging (e.g., CT or MRI).
  • imaging including feedback and monitoring from backscatter from bubble clouds may be used as a method to determine immediately if the histotripsy process has been initiated, is being properly maintained, or even if it has been extinguished.
  • this method enables continuously monitored in real time drug delivery, tissue erosion, and the like.
  • the method also can provide feedback permitting the histotripsy process to be initiated at a higher intensity and maintained at a much lower intensity.
  • backscatter feedback can be monitored by any transducer or ultrasonic imager. By measuring feedback for the therapy transducer, an accessory transducer can send out interrogation pulses or be configured to passively detect cavitation.
  • the nature of the feedback received can be used to adjust acoustic parameters (and associated system parameters) to optimize the drug delivery and/or tissue erosion process.
  • imaging including feedback and monitoring from backscatter, and speckle reduction, may be configured in the system.
  • speckle reduction Since the amount of speckle reduction is related to the amount of tissue subdivision, it can be related to the size of the remaining tissue fragments. When this size is reduced to sub-cellular levels, no cells are assumed to have survived. So, treatment can proceed until a desired speckle reduction level has been reached. Speckle is easily seen and evaluated on standard ultrasound imaging systems. Specialized transducers and systems, including those disclosed herein, may also be used to evaluate the backscatter changes. [0081] Further, systems comprising feedback and monitoring via speckle, and as means of background, an image may persist from frame to frame and change very little as long as the scatter distribution does not change and there is no movement of the imaged object.
  • This family of techniques can operate as detectors of speckle statistics changes. For example, the size and position of one or more speckles in an image will begin to decorrelate before observable speckle reduction occurs. Speckle decorrelation, after appropriate motion compensation, can be a sensitive measure of the mechanical disruption of the tissues, and thus a measure of therapeutic efficacy.
  • This feedback and monitoring technique may permit early observation of changes resulting from the acoustic cavitation/histotripsy process and can identify changes in tissue before substantial or complete tissue effect (e.g., erosion occurs).
  • this method may be used to monitor the acoustic cavitation/histotripsy process for enhanced drug delivery where treatment sites/tissue is temporally disrupted, and tissue damage/erosion is not desired.
  • this may comprise speckle decorrelation by movement of scatters in an increasingly fluidized therapy volume. For example, in the case where partial or complete tissue erosion is desired.
  • acoustic cavitation/histotripsy effect (homogenized, disrupted, or eroded)
  • its mechanical properties change from a soft but interconnected solid to a viscous fluid 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.
  • an ultrasound pulse can be used to produce a force (i.e., a radiation force) on a localized volume of tissue.
  • the tissue response (displacements, strains, and velocities) can change significantly during histotripsy treatment allowing the state of tissue disruption to be determined by imaging or other quantitative means.
  • Systems may also comprise feedback and monitoring via shear wave propagation changes.
  • the subdivision of tissues makes the tissue more fluid and less solid and fluid systems generally do not propagate shear waves.
  • the extent of tissue fluidization provides opportunities for feedback and monitoring of the histotripsy process.
  • ultrasound and MRI imaging systems can be used to observe the propagation of shear waves. The extinction of such waves in a treated volume is used as a measure of tissue destruction or disruption.
  • the system and supporting sub-systems may be used to generate and measure the interacting shear waves. For example, two adjacent ultrasound foci might perturb tissue by pushing it in certain ways. If adjacent foci are in a fluid, no shear waves propagate to interact with each other.
  • the interaction would be detected with external means, for example, by a difference frequency only detected when two shear waves interact nonlinearly, with their disappearance correlated to tissue damage.
  • the system may be configured to use this modality to enhance feedback and monitoring of the acoustic cavitation/histotripsy procedure.
  • a tissue volume is subdivided, its effect on acoustic cavitation/histotripsy (e.g., the bubble cloud here) is changed.
  • bubbles may grow larger and have a different lifetime and collapse changing characteristics in intact versus fluidized tissue. Bubbles may also move and interact after tissue is subdivided producing larger bubbles or cooperative interaction among bubbles, all of which can result in changes in acoustic emission. These emissions can be heard during treatment and they change during treatment. Analysis of these changes, and their correlation to therapeutic efficacy, enables monitoring of the progress of therapy, and may be configured as a feature of the system.
  • an impedance map of a therapy site can be produced based upon the spatial electrical characteristics throughout the therapy site.
  • Imaging of the conductivity or permittivity of the therapy site of a patient can be inferred from taking skin surface electrical measurements.
  • Conducting electrodes are attached to a patient's skin and small alternating currents are applied to some or all of the electrodes.
  • One or more known currents are injected into the surface and the voltage is measured at a number of points using the electrodes.
  • the process can be repeated for different configurations of applied current.
  • the resolution of the resultant image can be adjusted by changing the number of electrodes employed.
  • a measure of the electrical properties of the therapy site within the skin surface can be obtained from the impedance map, and changes in and location of the acoustic cavitation/histotripsy (e.g., bubble cloud, specifically) and histotripsy process can be monitored using this as configured in the system and supporting sub-systems.
  • the acoustic cavitation/histotripsy e.g., bubble cloud, specifically
  • histotripsy process can be monitored using this as configured in the system and supporting sub-systems.
  • the user may be allowed to further select, annotate, mark, highlight, and/or contour, various regions of interest or treatment sites, and defined treatment targets (on the image(s)), of which may be used to command and direct the system where to image, test and/or treat, through the system software and user interfaces and displays.
  • the user may use a manual ultrasound probe (e.g., diagnostic hand-held probe) to conduct the procedure.
  • the system may use a robot and/or electromechanical positioning system to conduct the procedure, as directed and/or automated by the system, or conversely, the system can enable combinations of manual and automated uses.
  • the system may further include the ability to conduct image registration, including imaging and image data set registration to allow navigation and localization of the system to the patient, including the treatment site (e.g., tumor, critical structure, bony anatomy, anatomy and identifying features of, etc.).
  • the system allows the user to image and identify a region of interest, for example the liver, using integrated ultrasound, and to select and mark a tumor (or surrogate marker of) comprised within the liver through/displayed in the system software, and wherein said system registers the image data to a coordinate system defined by the system, that further allows the system’s Therapy and Robotics sub-systems to deliver synchronized acoustic cavitation/histotripsy to said marked tumor.
  • the system may comprise the ability to register various image sets, including those previously disclosed, to one another, as well as to afford navigation and localization (e.g., of a therapy transducer to a CT or MRI/ultrasound fusion image with the therapy transducer and Robotics sub-system tracking to said image).
  • various image sets including those previously disclosed, to one another, as well as to afford navigation and localization (e.g., of a therapy transducer to a CT or MRI/ultrasound fusion image with the therapy transducer and Robotics sub-system tracking to said image).
  • the system may also comprise the ability to work in a variety of interventional, endoscopic and surgical environments, including alone and with other systems (surgical/laparoscopic towers, vision systems, endoscope 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.), of also which may work with, or comprise various optical imaging capabilities (e.g., fiber and or digital).
  • systems surgical/laparoscopic towers, vision systems, endoscope 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.), of also which may work with, or comprise various optical imaging capabilities (e.g., fiber and or digital).
  • the disclosed system may be configured to work with these systems, in some embodiments working alongside them in concert, or in other embodiments where all or some of the system may be integrated into the above systems/platforms (e.g., acoustic cavitation/histotripsy-enabled endoscope system or laparoscopic surgical robot).
  • a therapy transducer may be utilized at or around the time of use, for example, of an optically guided endoscope/bronchoscope, or as another example, at the time a laparoscopic robot (e.g., Intuitive Da Vinci* Xi system) is viewing/manipulating a tissue/treatment site.
  • these embodiments and examples may include where said other systems/platforms are used to deliver (locally) fluid to enable the creation of a man-made acoustic window, where on under normal circumstances may not exist (e.g., fluidizing a segment or lobe of the lung in preparation for acoustic cavitation/histotripsy via non-invasive transthoracic treatment (e.g., transducer externally placed on/around patient).
  • Systems disclosed herein may also comprise all or some of their sub-system hardware packaged within the other system cart/console/systems described here (e.g., acoustic cavitation/histotripsy system and/or sub-systems integrated and operated from said navigation or laparoscopic system).
  • the system may also be configured, through various aforementioned parameters and other parameters, to display real-time visualization of a bubble cloud in a spatial-temporal manner, including the resulting tissue effect peri/post-treatment from tissue/bubble cloud interaction, wherein the system can dynamically image and visualize, and display, the bubble cloud, and any changes to it (e.g., decreasing or increasing echogenicity), which may include intensity, shape, size, location, morphology, persistence, etc.
  • any changes to it e.g., decreasing or increasing echogenicity
  • These features may allow users to continuously track and follow the treatment in real-time in one integrated procedure and interface/system, and confirm treatment safety and efficacy on the fly (versus other interventional or surgical modalities, which either require multiple procedures to achieve the same, or where the treatment effect is not visible in real-time (e.g., radiation therapy), or where it is not possible to achieve such (e.g., real-time visualization of local tissue during thermal ablation), and/or where the other procedure further require invasive approaches (e.g., incisions or punctures) and iterative imaging in a scanner between procedure steps (e.g., CT or MRI scanning).
  • interventional or surgical modalities which either require multiple procedures to achieve the same, or where the treatment effect is not visible in real-time (e.g., radiation therapy), or where it is not possible to achieve such (e.g., real-time visualization of local tissue during thermal ablation), and/or where the other procedure further require invasive approaches (e.g., incisions or punctures) and iterative imaging in a
  • They system may comprise various Robotic sub-systems and components, including but not limited to, one or more robotic arms and controllers, which may further work with other sub-systems or components of the system to deliver and monitor acoustic cavitation/histotripsy.
  • robotic arms and control systems may be integrated into one or more Cart configurations.
  • one system embodiment may comprise a Cart with an integrated robotic arm and control system, and Therapy, Integrated Imaging and Software, where the robotic arm and other listed sub-systems are controlled by the user through the form factor of a single bedside Cart.
  • the Robotic sub-system may be configured in one or more separate Carts, that may be a driven in a master/slave configuration from a separate master or Cart, wherein the robotically-enabled Cart is positioned bed/patient-side, and the Master is at a distance from said Cart.
  • Disclosed robotic arms may be comprised of a plurality of joints, segments, and degrees of freedom and may also include various integrated sensor types and encoders, implemented for various use and safety features.
  • Sensing technologies and data may comprise, as an example, vision, potentiometers, position/localization, kinematics, force, torque, speed, acceleration, dynamic loading, and/or others.
  • sensors may be used for users to direct robot commands (e.g., hand gesture the robot into a preferred set up position, or to dock home). Additional details on robotic arms can be found in U.S. Patent Pub. No. 2013/0255426 to Kassow et al., which is disclosed herein by reference in its entirety.
  • the robotic arm receives control signals and commands from the robotic control system, which may be housed in a Cart.
  • the system may be configured to provide various functionalities, including but not limited to, position, tracking, patterns, triggering, and events/actions.
  • Position may be configured to comprise fixed positions, pallet positions, time- controlled positions, distance-controlled positions, variable-time controlled positions, variabledistance controlled positions.
  • Tracking may be configured to comprise time-controlled tracking and/or distance-controlled tracking.
  • the patterns of movement may be configured to comprise intermediate positions or waypoints, as well as sequence of positions, through a defined path in space.
  • Triggers may be configured to comprise distance measuring means, time, and/or various sensor means including those disclosed herein, and not limited to, visual/imaging-based, force, torque, localization, energy/power feedback and/or others.
  • Events/actions may be configured to comprise various examples, including proximity -based (approaching/departing a target object), activation or de-activation of various end-effectors (e.g., therapy transducers), starting/stopping/pausing sequences of said events, triggering or switching between triggers of events/actions, initiating patterns of movement and changing/toggling between patterns of movement, and/or time-based and temporal over the defined work and time-space.
  • proximity -based approaching/departing a target object
  • activation or de-activation of various end-effectors e.g., therapy transducers
  • starting/stopping/pausing sequences of said events e.g., triggering or switching between triggers of events/actions, initiating patterns of movement and changing/toggling between patterns of movement, and/or time-based and temporal over the defined work and time-space.
  • the system comprises a three degree of freedom robotic positioning system, enabled to allow the user (through the software of the system and related user interfaces), to micro-position a therapy transducer through X, Y, and Z coordinate system, and where gross macro-positioning of the transducer (e.g., aligning the transducer on the patient’s body) is completed manually.
  • the robot may comprise 6 degrees of freedom including X, Y, Z, and pitch, roll and yaw.
  • the Robotic subsystem may comprise further degrees of freedom, that allow the robot arm supporting base to be positioned along a linear axis running parallel to the general direction of the patient surface, and/or the supporting 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, Coupling sub-system, additional rob ots/rob otic arms and/or additional surgical systems, including but not limited to, surgical towers, imaging systems, endoscopic/laparoscopic systems, and/or other.
  • One or more robotic arms may also comprise various features to assist in maneuvering and modifying the arm position, manually or semi-manually, and of which said features may interface on or between the therapy transducer and the most distal joint of the robotic arm.
  • the feature is configured to comprise a handle allowing maneuvering and manual control with one or more hands.
  • the handle may also be configured to include user input and electronic control features of the robotic arm, to command various drive capabilities or modes, to actuate the robot to assist in gross or fine positioning of the arm (e.g., activating or deactivating free drive mode).
  • the work-flow for the initial positioning of the robotic arm and therapy head can be configured to allow either first positioning the therapy transducer/head in the coupling solution, with the therapy transducer directly interfaced to the arm, or in a different work-flow, allowing the user to set up the coupling solution first, and enabling the robot arm to be interfaced to the therapy transducer/coupling solution as a later/terminal set up step.
  • the robotic arm may comprise a robotic arm on a laparoscopic, single port, endoscopic, hybrid or combination of, and/or other robot, wherein said robot of the system may be a slave to a master that controls said arm, as well as potentially a plurality of other arms, equipped to concurrently execute other tasks (vision, imaging, grasping, cutting, ligating, sealing, closing, stapling, ablating, suturing, marking, etc.), including actuating one or more laparoscopic arms (and instruments) and various histotripsy system components.
  • a laparoscopic robot may be utilized to prepare the surgical site, including manipulating organ position to provide more ideal acoustic access and further stabilizing said organ in some cases to minimize respiratory motion.
  • a second robotic arm may be used to deliver non-invasive acoustic cavitation through a body cavity, as observed under real-time imaging from the therapy transducer (e.g., ultrasound) and with concurrent visualization via a laparoscopic camera.
  • the therapy transducer e.g., ultrasound
  • a similar approach may be utilized with a combination of an endoscopic and non-invasive approach, and further, with a combination of an endoscopic, laparoscopic and non-invasive approach.
  • the system may comprise various software applications, features and components which allow the user to interact, control and use the system for a plethora of clinical applications.
  • the Software may communicate and work with one or more of the sub-systems, including but not limited to Therapy, Integrated Imaging, Robotics and Other Components, Ancillaries and Accessories of the system.
  • the software may provide features and support to initialize and set up the system, service the system, communicate and import/ export/ store data, modify/manipulate/configure/control/command various settings and parameters by the user, mitigate safety and use-related risks, plan procedures, provide support to various configurations of transducers, robotic arms and drive systems, function generators and amplifier circuits/slaves, test and treatment ultrasound sequences, transducer steering and positioning (electromechanical and electronic beam steering, etc.), treatment patterns, support for imaging and imaging probes, manual and electromechanical/robotically-enabling movement of, imaging support for measuring/characterizing various dimensions within or around procedure and treatment sites (e.g., depth from one anatomical location to another, etc., pre-treatment assessments and protocols for measuring/characterizing in situ treatment site properties and conditions (e.g., acoustic cavitation/histotripsy thresholds and heterogeneity of), targeting and target alignment, calibration, marking/annotating, localizing/navigating, registering
  • the software user interfaces and supporting displays may comprise various buttons, commands, icons, graphics, text, etc., that allow the user to interact with the system in a user-friendly and effective manner, and these may be presented in an unlimited number of permutations, layouts and designs, and displayed in similar or different manners or feature sets for systems that may comprise more than one display (e.g., touch screen monitor and touch pad), and/or may network to one or more external displays or systems (e.g., another robot, navigation system, system tower, console, monitor, touch display, mobile device, tablet, etc.).
  • a display e.g., touch screen monitor and touch pad
  • external displays or systems e.g., another robot, navigation system, system tower, console, monitor, touch display, mobile device, tablet, etc.
  • the software may support the various aforementioned function generators (e.g., FPGA), amplifiers, power supplies and therapy transducers.
  • the software may be configured to allow users to select, determine and monitor various parameters and settings for acoustic cavitation/histotripsy, and upon observing/receiving feedback on performance and conditions, may allow the user to stop/start/modify said parameters and settings.
  • the software may be configured to allow users to select from a list or menu of multiple transducers and support the auto-detection of said transducers upon connection to the system (and verification of the appropriate sequence and parameter settings based on selected application).
  • the software may update the 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.
  • the software may provide error messages or warnings to the user if said therapy transducer, amplifier and/or function generator selections or parameters are erroneous, yield a fault or failure. This may further comprise reporting the details and location of such.
  • the software may be configured to allow users to select treatment sequences and protocols from a list or menu, and to store selected and/or previous selected sequences and protocols as associated with specific clinical uses or patient profiles.
  • Related profiles may comprise any associated patient, procedure, clinical and/or engineering data, and maybe used to inform, modify and/or guide current or future treatments or procedures/interventions, whether as decision support or an active part of a procedure itself (e.g., using serial data sets to build and guide new treatments).
  • the software may allow the user to evaluate and test acoustic cavitation/histotripsy thresholds at various locations in a user-selected region of interest or defined treatment area/volume, to determine the minimum cavitation thresholds throughout said region or area/volume, to ensure treatment parameters are optimized to achieve, maintain and dynamically control acoustic cavitation/histotripsy.
  • the system allows a user to manually evaluate and test threshold parameters at various points.
  • Said points may include those at defined boundary, interior to the boundary and center locations/positions, of the selected region of interest and treatment area/volume, and where resulting threshold measurements may be reported/displayed to the user, as well as utilized to update therapy parameters before treatment.
  • the system may be configured to allow automated threshold measurements and updates, as enabled by the aforementioned Robotics sub-system, wherein the user may direct the robot, or the robot may be commanded to execute the measurements autonomously.
  • Software may also be configured, by working with computer processors and one or more function generators, amplifiers and therapy transducers, to allow various permutations of delivering and positioning optimized acoustic cavitation/histotripsy in and through a selected area/volume.
  • This may include, but not limited to, systems configured with a fixed/natural focus arrangement using purely electromechanical positioning configuration(s), 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, high speed axial electronic beam steering with lateral electromechanical positioning, high speed beam steering in 3D space, various combinations of including with dynamically varying one or more acoustic cavitation/histotripsy parameters based on the aforementioned ability to update treatment parameters based on threshold measurements (e.g., dynamically adjusting amplitude across the treatment area/volume).
  • the system may comprise various other components, ancillaries 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 security, communication, integration into information systems including hospital information systems, cellular communication devices and modems, handheld wired or wireless controllers, goggles or glasses for advanced visualization, augmented or virtual reality applications, cameras, sensors, tablets, smart devices, phones, internet of things enabling capabilities, specialized 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.
  • the system may allow additional benefits, such as enhanced planning, imaging and guidance to assist the user.
  • the system may allow a user to create a patient, target and application specific treatment plan, wherein the system may be configured to optimize treatment parameters based on feedback to the system during planning, and where planning may further comprise the ability to run various test protocols to gather specific inputs to the system and plan.
  • Feedback may include various energy, power, location, position, tissue and/or other parameters.
  • the system may also be further configured and used to autonomously (and robotically) execute the delivery of the optimized treatment plan and protocol, as visualized under real-time imaging during the procedure, allowing the user to directly observe the local treatment tissue effect, as it progresses through treatment, and start/stop/modify treatment at their discretion.
  • Both test and treatment protocols may be updated over the course of the procedure at the direction of the user, or in some embodiments, based on logic embedded within the system.
  • HIFU high intensity focused ultrasound
  • HITU high intensity therapeutic ultrasound
  • boiling histotripsy thermal cavitation
  • the Therapy sub-system comprising in part, one or more amplifiers, transducers and power supplies, may be configured to allow multiple acoustic cavitation and histotripsy driving capabilities, affording specific benefits based on application, method and/or patient specific use. These benefits may include, but are not limited to, the ability to better optimize and control treatment parameters, which may allow delivery of more energy, with more desirable thermal profiles, increased treatment speed and reduced procedure times, enable electronic beam steering and/or other features.
  • This disclosure also includes novel systems and concepts as related to systems and sub-systems comprising new and “universal” amplifiers, which may allow multiple driving approaches (e.g., single and multi-cycle pulsing). In some embodiments, this may include various novel features to further protect the system and user, in terms of electrical safety or other hazards (e.g., damage to transducer and/or amplifier circuitry).
  • the system, and Therapy sub-system may include a plethora of therapy transducers, where said therapy transducers are configured for specific applications and uses and may accommodate treating over a wide range of working parameters (target size, depth, location, etc.) and may comprise a wide range of working specifications (detailed below).
  • Transducers may further adapt, interface and connect to a robotically-enabled system, as well as the Coupling sub-system, allowing the transducer to be positioned within, or along with, an acoustic coupling device allowing, in many embodiments, concurrent imaging and histotripsy treatments through an acceptable acoustic window.
  • the therapy transducer may also comprise an integrated imaging probe or localization sensors, capable of displaying and determining transducer position within the treatment site and affording a direct field of view (or representation of) the treatment site, and as the acoustic cavitation/histotripsy tissue effect and bubble cloud may or may not change in appearance and intensity, throughout the treatment, and as a function of its location within said treatment (e.g., tumor, healthy tissue surrounding, critical structures, adipose tissue, etc.).
  • an integrated imaging probe or localization sensors capable of displaying and determining transducer position within the treatment site and affording a direct field of view (or representation of) the treatment site, and as the acoustic cavitation/histotripsy tissue effect and bubble cloud may or may not change in appearance and intensity, throughout the treatment, and as a function of its location within said treatment (e.g., tumor, healthy tissue surrounding, critical structures, adipose tissue, etc.).
  • the systems, methods and use of the system disclosed herein may be beneficial to overcoming significant unmet needs in the areas of soft tissue ablation, oncology, immunooncology, advanced image guided procedures, surgical procedures including but not limited to open, laparoscopic, single incision, natural orifice, endoscopic, non-invasive, various combination of, various interventional spaces for catheter-based procedures of the vascular, cardiovascular pulmonary and/or neurocranial-related spaces, cosmetics/aesthetics, metabolic (e.g., type 2 diabetes), plastic and reconstructive, ocular and ophthalmology, orthopedic, gynecology and men’s health, and other systems, devices and methods of treating diseased, injured, undesired, or healthy tissues, organs or cells.
  • surgical procedures including but not limited to open, laparoscopic, single incision, natural orifice, endoscopic, non-invasive, various combination of, various interventional spaces for catheter-based procedures of the vascular, cardiovascular pulmonary and/or neurocranial-related spaces, cosmetics/aesthetics,
  • 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 prefocal tissue heating delivered to patients.
  • the disclosed system, methods of use, and use of the system may be conducted in a plethora of environments and settings, with or without various support systems such as anesthesia, including but not limited to, procedure suites, operating rooms, hybrid rooms, in and out-patient settings, ambulatory settings, imaging centers, radiology, radiation therapy, oncology, surgical and/or any medical center, as well as physician offices, mobile healthcare centers or systems, automobiles and related vehicles (e.g., van), aero and marine transportation vehicles such as planes and ships, and/or any structure capable of providing temporary procedure support (e.g., tent).
  • anesthesia including but not limited to, procedure suites, operating rooms, hybrid rooms, in and out-patient settings, ambulatory settings, imaging centers, radiology, radiation therapy, oncology, surgical and/or any medical center, as well as physician offices, mobile healthcare centers or systems, automobiles and related vehicles (e.g., van), aero and marine transportation vehicles such as planes and ships, and/or any structure capable of providing temporary procedure support (e.g., tent).
  • systems and/or sub-systems disclosed herein may also be provided as integrated features into other environments, for example, the direct integration of the histotripsy Therapy sub-system into a MRI scanner or patient surface/bed, wherein at a minimum the therapy generator and transducer are integral to such, and in other cases wherein the histotripsy configuration further includes a robotic positioning system, which also may be integral to a scanner or bed centered design.
  • Systems may include a variety of coupling subsystem embodiments, of which are enabled and configured to allow acoustic coupling to the patient to afford effective acoustic access for ultrasound visualization and acoustic cavitation/histotripsy (e.g., provide acoustic window and medium between the transducer(s) and patient, and support of). These may include different form factors of such, including open and enclosed device solutions, and some arrangements which may 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 directly integrated to the system (within the Cart), or may be in temporary/intermittent or continuous communication with the system, but externally situated in a separate device and/or cart.
  • acoustic medium e.g., temperature, dissolved gas content, level of particulate filtration, sterility, volume, composition, etc.
  • the coupling sub-system typically includes, at a minimum, coupling medium (e.g., degassed water or water solutions), a reservoir/container to contain said coupling medium, and a support structure (including interfaces to other surfaces or devices).
  • the coupling medium is water, and wherein the water may be conditioned before or during the procedure (e.g., chilled, degassed, filtered, etc.).
  • Various conditioning parameters may be employed based on the configuration of the system and its intended use/application.
  • the reservoir or ultrasound medium container UMC may be formed and shaped to various sizes and shapes, and to adapt/conform to the patient, allow the therapy transducer to engage/access and work within the acoustic medium, per defined and required working space (minimum volume of medium to allow the therapy transducer to be positioned and/or move through one or more treatment positions or patterns, and at various standoffs or depths from the patient, etc.), and wherein said reservoir or medium container may also mechanically support the load, and distribution of the load, through the use of a mechanical and/or electromechanical support structure. As a representative example, this may include a support frame.
  • the container may be of various shapes, sizes, curvatures, and dimensions, and may be formed of a variety of materials compositions (single, multiple, composites, etc.), of which may vary throughout.
  • the container or reservoir may include features such as films, drapes, membranes, bellows, etc. that may be insertable and removable, and/or fabricated within, of which may be used to conform to the patient and assist in confining/containing the medium within the container.
  • the container or reservoir may further contain various sensors (e.g., volume/fill level), drains (e.g., inlet/outlet), lighting (e.g., LEDs), markings (e.g., fill lines, set up orientations, etc.), text (e.g., labeling), etc.
  • the reservoir or medium container contains a sealable frame, of which a membrane and/or film may be positioned within, to afford a conformable means of contacting the reservoir (later comprising the treatment head/therapy transducer) as an interface to the patient, that further provides a barrier to the medium (e.g., water) between the patient and therapy transducer).
  • the membrane and/or film may include an opening, the patient contacting edge of which affords a fluid/mechanical seal to the patient, but in contrast allows medium communication directly with the patient (e.g., direct degassed water interface with patient).
  • the superstructure of the reservoir or medium container in both these examples may further afford the proximal portion of the structure (e.g., top) to be open or enclosed (e.g., to prevent spillage or afford additional features).
  • Disclosed membranes may be formed of various elastomers, viscoelastic polymers, thermoplastics, thermoplastic elastomers, thermoset polymers, silicones, urethanes, rigid/flexible co-polymers, block co-polymers, random block co-polymers, etc. Materials may be hydrophilic, hydrophobic, surface modified, coated, extracted, etc., and may also contain various additives to enhance performance, appearance or stability.
  • the thermoplastic elastomer may be styrene-ethylene-butylene-styrene (SEBS), or other like strong and flexible elastomers.
  • SEBS styrene-ethylene-butylene-styrene
  • the membrane form factor can be flat or pre-shaped prior to use.
  • the membrane could be inelastic (i.e., a convex shape) and pressed against the patient’s skin to acoustically couple the transducer to the tissue.
  • Systems and methods are further disclosed to control the level of contaminants (e.g., particulates, etc.) on the membrane to maintain the proper level of ultrasound coupling. Too many particulates or contaminants can cause scattering of the ultrasound waves. This can be achieved with removable films or coatings on the outer surfaces of the membrane to protect against contamination.
  • Said materials may be formed into useful membranes through molding, casting, spraying, ultrasonic spraying, extruding, and/or any other processing methodology that produces useful embodiments. They may be single use or reposable/reusable. They may be provided non- sterile, aseptically cleaned or sterile, where sterilization may be performed using any known method, including but not limited to ethylene oxide, gamma, e-beam, autoclaving, steam, peroxide, plasma, chemical, etc. Membranes can be further configured with an outer molded or over molded frame to provide mechanical stability to the membrane during handling including assembly, set up and take down of the coupling sub-system.
  • Various parameters of the membrane can be optimized for this method of use, including thickness, thickness profile, density, formulation (e.g., polymer molecular weight and copolymer ratios, additives, plasticizers, etc.), including optimizing specifically to maximize acoustic transmission properties, including minimizing impact to cavitation initiation threshold values, and/or ultrasound imaging artifacts, including but not limited to membrane reflections, as representative examples.
  • Open reservoirs or medium containers may comprise various methods of filling, including using pre-prepared medium or water, that may be delivered into the containers, in some cases to a defined specification of water (level of temperature, gas saturation, etc.), or they may comprise additional features integral to the design that allow filling and draining (e.g., ports, valves, hoses, tubing, fittings, bags, pumps, etc.). These features may be further configured into or to interface to other devices, including for example, a fluidics system.
  • the fluidics system may be an in-house medium preparation system in a hospital or care setting room, or conversely, a mobile cart-based system which can prepare and transport medium to and from the cart to the medium container, etc.
  • Enclosed iterations of the reservoir or medium container may comprise various features for sealing, in some embodiments sealing to a proximal/top portion or structure of a reservoir/container, or in other cases where sealing may comprise embodiments that seal to the transducer, or a feature on the transducer housings. Further, some embodiments may comprise the dynamic ability to control the volume of fluid within these designs, to minimize the potential for air bubbles or turbulence in said fluid and to allow for changes in the focal length to the target area without moving the transducer. As such, integrated features allowing fluid communication, and control of, may be provided (ability to provide/remove fluid on demand), including the ability to monitor and control various fluid parameters, some disclosed above.
  • the overall system, and as part, the Coupling sub-system may comprise a fluid conditioning system, which may contain various electromechanical devices, systems, power, sensing, computing, pumping, filtering and control systems, etc.
  • the reservoir may also be configured to receive signals that cause it to deform or change shape in a specific and controlled manner to allow the target point to be adjusted without moving the transducer.
  • Coupling support systems may include various mechanical support devices to interface the reservoir/container and medium to the patient, and the workspace (e.g., bed, floor, etc.).
  • the support system comprises a mechanical arm with 3 or more degrees of freedom.
  • Said arm may have a proximal interface with one or more locations (and features) of the bed, including but not limited to, the frame, rails, customized rails or inserts, as well as one or more distal locations of the reservoir or container.
  • the arm may also be a feature implemented on one or more Carts, wherein Carts may be configured in various unlimited permutations, in some cases where a Cart only comprises the role of supporting and providing the disclosed support structure.
  • the support structure and arm may be a robotically-enabled arm, implemented as a stand-alone Cart, or integrated into a Cart further comprising two or more system sub-systems, or where in the robotically-enabled arm is an arm of another robot, of interventional, surgical or other type, and may further comprise various user input features to actuate/control the robotic arm (e.g., positioning into/within coupling medium) and/or Coupling solution features (e.g., filling, draining, etc.).
  • the support structure robotic arm positional encoders may be used to coordinate the manipulation of the second arm (e.g. comprising the therapy transducer/treatment head), such as to position the therapy transducer to a desired/known location and pose within the coupling support structure.
  • histotripsy delivery including robotic histotripsy delivery, wherein one or more histotripsy therapy transducers may be configured to acoustically couple to a patient, using a completely sealed approach (e.g., no acoustic medium communication with the patient’s skin) and allowing the one or more histotripsy transducers to be moved within the coupling solution without impeding the motion/movement of the robotic arm or interfering/ disturbing the coupling interface, which could affect the intended treatment and/or target location.
  • a completely sealed approach e.g., no acoustic medium communication with the patient’s skin
  • histotripsy acoustic and patient coupling systems and methods to enable histotripsy therapy/treatment, as envisioned in any setting, from interventional suite, operating room, hybrid suites, imaging centers, medical centers, office settings, mobile treatment centers, and/or others, as non-limiting examples.
  • the following disclosure further describes novel systems used to create, control, maintain, modify/enhance, monitor and setup/takedown acoustic and patient coupling systems, in a variety of approaches, methods, environments, architectures and work-flows.
  • the disclosed novel systems may allow for a coupling medium, in some examples degassed water, to be interfaced between a histotripsy therapy transducer and a patient, wherein the acoustic medium provides sufficient acoustic coupling to said patient, allowing the delivery of histotripsy pulses through a user desired treatment location (and volume), where the delivery may require physically moving the histotripsy therapy transducer within a defined work-space comprising the coupling medium, and also where the coupling system is configured to allow said movement of the therapy transducer (and positioning system, e.g., robot) freely and unencumbered from by the coupling support system (e.g., a frame or manifold holding the coupling medium).
  • the coupling support system e.g., a frame or manifold holding the coupling medium.
  • the disclosed histotripsy acoustic and patient coupling systems may include one or more of the following sub-systems and components, an example of which is depicted in FIG. 2, including but not limited to 1) a membrane/barrier film to provide an enclosed, sealed and conformal patient coupling and histotripsy system interface, 2) a frame body to retain the membrane and provide sufficient work and head space for a histotripsy therapy transducers required range of motion (x, y and z, pitch, roll and yaw), 3) a sufficient volume of ultrasound medium to afford acoustic coupling and interfaces to a histotripsy therapy transducer and robotic arm, 4) one or more mechanical support arms to allow placement, positioning and load support of theframe body, membrane, and medium, and 5) a fluidics system to prepare, provide and remove ultrasound medium(s) from the frame body and membrane, and 6) a membrane constraint.
  • a membrane/barrier film to provide an enclosed, sealed and conformal patient coupling and histotripsy system interface
  • the coupling system may be fully sealed, and in other embodiments and configurations, it may be partially open to afford immediate access (physical and/or visual).
  • the acoustic and patient coupling systems and sub-systems may further include various features and functionality, and associated work-flows, and may also be configured in a variety of ways to enable histotripsy procedures as detailed below.
  • FIG. 2 illustrates one embodiment of a histotripsy therapy and imaging system 200, including a coupling assembly 212.
  • a histotripsy therapy and imaging system can include a therapy transducer 202, an imaging system 204, a robotic positioning arm 208, and a fluidics cart 210.
  • the therapy and/or imaging transducers can be housed in a coupling assembly 212 which can include a reservoir or medium container 213, which includes a frame body 215 and a coupling membrane 214, and a membrane constraint 216 configured to prevent the membrane from expanding too far from the transducer.
  • the coupling assembly can be filled with an acoustic coupling medium such as a fluid or a gel.
  • the membrane constraint can be, for example, a semi-rigid or rigid material configured to restrict expansion/movement of the membrane caused by the addition of the coupling medium into the coupling assembly. In some embodiments, the membrane constraint is not used, and the elasticity and tensile strength of the membrane prevent over expansion.
  • the coupling membrane can be a mineral-oil infused SEBS membrane to prevent direct fluid contact with the patient’s skin.
  • the coupling assembly 212 is supported by a mechanical support arm 218 which can be load bearing in the x-y plane but allow for manual or automated z-axis adjustment.
  • the mechanical support arm can be attached to the floor, the patient table, or the fluidics cart 210.
  • the mechanical support is designed and configured to conform and hold the coupling membrane 214 in place against the patient’s skin while still allowing movement of the therapy/imaging transducer relative to the patient and also relative to the coupling membrane 214 with the robotic positioning arm 208.
  • the fluidics cart 210 can include additional features, including a fluid tank 220, a cooling and degassing system, and a programmable control system.
  • the fluidics cart is configured for external loading of the coupling membrane with automated control of fluidic sequences. Further details on the fluidics cart are provided below.
  • FIGS. 3 A-3G depict a reservoir or UMC (ultrasound medium container) 312 including at least a frame body 330 and a coupling membrane 314.
  • the frame body 330 includes an upper frame body portion 335 (shown in more detail in FIGS. 3B- 3D) and a lower frame body portion 360 (shown in more detail in FIGS. 3E-3G).
  • a plurality of constraint connectors 364 may be positioned intermittently around an exterior of the lower frame body 360 for attaching a membrane constraint (not shown in FIGS. 3A-3G) to the frame body 330.
  • At least a portion of the coupling membrane 314 being housed within the lower frame body 360 and extending across a lower frame body opening 366.
  • FIGS. 3B-3D depict the upper frame body 335 of the coupling assembly or UMC 312.
  • the upper frame body 335 includes an upper frame sidewall 340 extending between a sidewall upper edge 342 and a sidewall lower edge 344.
  • the upper edge 342 may include a ledge 343 extending outwardly away (and generally perpendicular) from an exterior 335b of the upper frame body 335 (and/or away from an upper frame cavity 346).
  • the upper ledge 342 may be configured to be seated on a frame support bracket (not shown in FIGS. 3A-3G) as provided in more detail hereinbelow.
  • a perimeter p 0 of the sidewall upper edge 342 may be larger than a perimeter pi of the lower edge 344 forming an upper frame body 335 defining a truncated cone or bucket shape.
  • An interior 335a of the upper frame body 335 (and/or upper frame sidewall 340) defines an upper frame cavity 346 of sufficient height H (and/or depth) to freely accommodate at least partially therein the one or more transducers and the coupling medium as described herein (and as shown in FIG. 2).
  • An exterior 335b of the upper frame body 335 includes a pier 347 configured to connect the reservoir or UMC 312 (and/or coupling assembly) to a mechanical support arm, either directly (FIG. 2) or via an intermediary frame support bracket (FIGS. 7A-9).
  • the pier 347 defines a shaped body extending outwardly and generally perpendicular from the exterior 335b of the frame body 335 (and/or sidewall 340).
  • the pier 347 may include a pier cavity 348 therein.
  • the pier cavity 348 being configured to receive a portion of the mechanical support arm and/or the frame support bracket therein to releasably secure the reservoir or UMC (and/or coupling assembly) to the mechanical support arm.
  • pier 347 and/or pier cavity 348 do not pass through the interior 335a of the frame body 335 and thus is not connected to the upper frame cavity 346.
  • a face 347a of the pier 347 extends generally perpendicular to one or more of the upper edge 342, lower edge 344, and/or upper ledge 343.
  • the pier 347 and/or the pier cavity 348 may define any shape suitable for engaging the mechanical support arm and/or the frame support bracket. As shown, in some embodiments, both the pier 347 and the pier cavity 348 may define a generally rectangular shape. However, in some embodiments, the pier body 347 and pier cavity 348 may define different shapes, such as triangular, pentagonal, hexagonal, heptagonal, octagonal, circular, elliptical, and the like.
  • the pier body 347 may be reinforced with one or more reinforcement rods 349 made of a material more rigid than the reservoir or UMC 312 and/or pier 347 to reinforce the connection between the reservoir or UMC 312 and one or more of the mechanical support arms 218 or the one or more frame support brackets 370.
  • the reinforced rods 349 may be made of stainless steel.
  • the reinforced rods 349 may be distributed symmetrical about the pier 347, such as being located in each corner of a rectangular pier.
  • FIGS. 3E-3G depict the lower frame body 360 of the reservoir or UMC 312.
  • the lower frame body 360 defining a lower frame body opening 366 configured to be covered and/or sealed by the coupling membrane.
  • the lower frame body 360 includes a plurality of the constraint connectors 364 and clamp latches 352 intermittently spaced about an exterior 360b of the lower frame body 360.
  • each clamp latch 352 extends outwardly and downwardly from the exterior 360b of the lower frame body 360.
  • the clamp latch 352 is configured to interact with the clamp handle 353 attached to the exterior 335b of the upper frame body 335 to secure the upper and lower frame bodies 335, 360 together to form the assembly or UMC 312.
  • the lower frame includes several posts 355 which extend outward and upward from the lower frame body 360 to assist in aligning the upper and lower bodies 335, 360 together.
  • the upper frame 335 includes corresponding holes or voids 353 for receiving the posts 355 therein (Figs. 3B and 3D).
  • the frame lower body 360 includes a lower channel or step 368 defined therein.
  • the lower channel or step 368 surrounds the lower body frame opening 366 and is configured to receive and maintain a portion of at least one, if not all, of a gasket, the membrane, or the guide wall of the upper frame body.
  • each constraint connector 364 extends outwardly and upwardly from the exterior 360b of the lower frame body 360. This outward and upward design allows the constraint, via the pores/openings of the constraint, to attach to and/or hang from the reservoir or UMC 312 (and/or the lower frame body 360) to aid in restraining the membrane.
  • the constraint connectors 264 define a generally rectangular shape with rounded or curved comers.
  • the constraint connectors 364 may define any suitable shape including but not limited to triangular (FIG. 4A), trapezoidal (FIG. 4B), circular (FIG. 4C), castellated (FIG.4D), and/or hooked (FIG. 4E).
  • FIGS. 5A-5B depict a frame clamp 350 in an open, i.e., unclamped position and a closed, i.e., clamped position, configuration respectively.
  • the frame clamp 350 includes a clamp base 351 secured to an exterior 335b of the upper frame body 335, a clamp latch 352 secured to the exterior 360b of the lower frame body 360, a clamp handle 353 pivotably connected to the clamp base 351, and a connecting rod 354 connected to the handle 353 on one end and the latch 352 on the other.
  • the connecting rod is threaded, such as a screw or bolt
  • the handle 353 may further include a threaded receiver 535a for interacting with the threaded connecting rod 354.
  • FIG. 6 depicts another a reservoir or UMC 612 including at least a frame body 630 and a coupling membrane 614.
  • the reservoir or UMC 612 of FIG. 6 is similar to the reservoir or UMC 312 of FIGS. 3 A-3G, except the upper frame body 635 and the lower frame body 660 are one-piece and the constraint connectors 664 extend upwardly and outwardly from the upper frame body 635.
  • the reservoir or UMC 612 (and/or coupling assembly) may or may not include at least one frame clamp 650.
  • FIGS. 7A-7C depict a frame support bracket 770 configured to be included in any of the reservoirs or UMCs (and/or coupling assemblies) as described herein.
  • the frame support bracket 770 includes one or more support wing portions 780, 790 extending from a central bracket portion 772.
  • the central bracket portion 772 being configured to be affixed to and/or matingly engage with the shaped pier 347 of the upper frame body 335 as described herein in FIGS. 3A-3G.
  • the central portion 772 includes two or more inner tabs 774, 776, extending inward from an inner surface 772a of the central structure portion 772 and spaced apart to define a tab cavity 777 therebetween.
  • An inner cavity ledge 778 extends along a top of the tab cavity 777 and connects the inner tabs 774, 776.
  • the inner cavity ledge 778 is configured to sit on and/or be seated on top of the shaped pier 347 of the upper frame 335 of FIGS. 3A-3G.
  • the central portion 772 can further be fastened to the pier 347 via any suitable fastening manner including but not limited to screws, bolts, rivets, adhesives, and the like.
  • the central portion 772 further includes an outer tab 779 extending outwardly away from an outer surface 772b of the central structure 772 and generally centered on the outer surface 772b of the central portion 772. The outer tab 779 being configured to attach the support bracket 770 (and/or the frame body, coupling assembly, reservoir, UMC) to a mechanical support arm.
  • the outer tab 779 may be centered longitudinally between the two inner tabs 774, 776, while the outer tab 779 extends from an opposite side of the bracket 770 than the inner tabs 774, 776.
  • the frame support bracket may define a generally C-shaped bracket (from a top or bottom view).
  • the support bracket 770 may also include a first support wing 780 and a second support wing 790.
  • the first support wing 780 extending in a curved manner from a first side of the central bracket portion 772.
  • the first support wing 780 extending between a first fixed end portion 782 and a first free end portion 784 with a first central wing portion 783 positioned therebetween.
  • the second support wing 790 extending in a curved manner from a second side of the central bracket portion 772.
  • the second support wing 790 extending between a second fixed end 792 and a second free end 794 with a second central wing portion 793 positioned therebetween.
  • the first and second support wings 780, 790 are configured to extend circumferentially around the outer perimeter of the upper frame body 335.
  • the first central wing portion 783 may be thinner and/or define a smaller height than one or both of the first fixed end portion 782 or the first free end portion 784.
  • the second central wing portion 793 may be thinner and/or define a smaller height than one or both of the second fixed end portion 792 or the second free end portion 794.
  • the outer tab 779 of the bracket 770 may include one or more apertures 795, 796 defined therethrough.
  • a first outer tab locking aperture 795 may be configured to receive and maintain a fastener, such as a knurled knob (see FIGS. 9A-9C), therein to secure the bracket 770 (and/or the frame, reservoir, UMC) to a mechanical support arm (not shown in FIG. 7C).
  • a second outer tab adjustment aperture 796 may be configured to receive and maintain an adjustment knob (see FIGS. 9A-9C) therein for adjusting the tilt of the bracket 770 (and/or the frame, reservoir, UMC) relative to a patient and/or mechanical support arm.
  • FIGS. 8A-8C depict an upper frame body 835 of reservoir or UMC (and/or coupling assembly) including a frame support bracket 870.
  • the support bracket 870 being secured to the frame body 835 by bracket connectors 845 extending from an exterior 835b of the frame body 835 and above the frame clamps 850.
  • the support bracket 870 being configured to reinforce and/or stabilize the location of the frame body 835 (and/or coupling assembly, reservoir, or UMC) relative to a patient which can be important during histotripsy and/or acoustic cavitation.
  • the frame support bracket 870 is secured to the frame body 835 such that an upper ledge 843 of the frame body 835 is seated on a top wall 871 of the support bracket 870.
  • the thicker free end portions 884, 894 and the fixed end portions 882, 892 may be located directly over the intermittently spaced clamps 850, which may be the areas of the frame body 835 wherein more stress is applied.
  • the support wings 880, 890 of the support bracket 870 wrap circumferentially around the outer perimeter p of the frame body 835 (and/or assembly, reservoir, or UMC).
  • the bracket extends around about 20 to 75% of the outer perimeter of the ledge.
  • the bracket extends around about 25 to 65% of the outer perimeter of the ledge.
  • the bracket extends around from about 30 to 50% of the outer perimeter of the ledge.
  • the frame support bracket may be made of the same material of the frame body.
  • the frame support bracket and the frame body may be made of rigid plastic.
  • the frame support may comprise a stronger or higher modulus material, which may be different than the upper frame body.
  • the frame support 770 includes polycarbonate or other higher modulus polymers or plastics which enable acoustic coupling.
  • a metallic frame support may also be employed.
  • a gasket 828 such as an O-ring, may be positioned around an alignment member 837 of the upper frame body portion 835 to aid in sealing a portion of a coupling membrane (not shown) around the alignment member 837.
  • the gasket 828, alignment member 837 and the portion of the coupling membrane designed to be received within the lower channel or step of the lower frame body portion to seal the upper frame body cavity.
  • the upper frame 835 may further include one or more alignment tabs 855 extending therefrom to further aid in properly seating the membrane on the frame 835.
  • a frame support bracket 970 may include a first and second wing portion 980, 990 extending circumferentially around about half of the frame body 935 wherein a thickness or height of the fixed end wing portion 982, 992 and the central wing portion 972 are generally equal while the thickness or height of the free end portion 984, 994 narrows and/or tapers to a smaller thickness and/or height than the rest of the bracket 970.
  • the support bracket 970 being secured to the frame body 935 on an interior face of the bracket (and/or central bracket portion 972 or wing portions 980, 990) and a support arm handle 924 of a mechanical support arm 918 via an exterior face of the central bracket portion 972.
  • the support arm handle 924 includes a knurled knob 925, a handle trigger 926, and a pivotable lever 927.
  • the knurled knob 925 being configured to secure and/or lock the bracket 970 (and/or upper frame 935, lower frame 960, reservoir 930 attached thereto) to the mechanical support arm 918.
  • the knurled knob 925 includes a threaded pin 925a (in phantom) extending therefrom and designed to be rotated into the outer tab locking aperture (not shown in FIGS. 9A-9C) of the bracket 970.
  • the handle trigger 926 is configured to rotate the support arm handle 924 (and/or the bracket 970, upper frame 935, reservoir attached thereto) generally 180 degrees when actuated.
  • a first actuation of the handle trigger 926 may cause the support arm handle 924 (and/or the bracket 970, frame 935, reservoir attached thereto) to rotate from an upright position (FIG. 9A) to an upside down position (FIGS. 9B-9C).
  • a second actuation of the handle trigger 926 may cause the support arm handle 924 (and/or the bracket 970, frame 935, reservoir attached thereto) to rotate from an upside down position (FIGS. 9B-9C) to an upright position (FIG. 9A).
  • actuation of the handle trigger 926 may also enable rotation of a portion of the mechanical support arm 918.
  • This rotational feature of the handle 924 can be useful, in some embodiments, when loading or connecting a membrane, gasket, and/or lower frame (not shown) to an upper frame 935.
  • a membrane can be easily seated over the alignment member 937, optionally with one or more (i.e., two, three, or four) holes in the membrane lined up with or adjacent to the one or more (i.e., two, three, or four) alignment tabs 955.
  • an outer gasket 928 can be positioned around the perimeter of the membrane before a lower frame is added and clamped to the upper frame to form a reservoir or UMC.
  • an inner gasket may also be used to aid in sealing the membrane.
  • the pivotable lever 927 is configured to fine tune/adjust (via tilting and/or pivoting) the orientation of the coupling assembly, including the bracket 970, upper and lower frames 935 and 960, reservoir 930 attached thereto.
  • the support arm handle 924 does not rotate via pivotable lever 927.
  • the pivotable lever 927 is configured to move about the handle trigger 926 to rotate or pivot the entire coupling assembly including upper and lower frames 935 and 960, the bracket 970 and reservoir 930 attached thereto) up tol5 degrees off-axis in either direction as needed.
  • the frame support bracket may be made of a material more rigid than the material of the frame body.
  • FIGS. 10A-10C illustrate embodiments of a membrane constraint 316, 416 which is referred to herein as a constraint device.
  • the constraint device of the present disclosure comprises a mesh structure with open pores having varied geometrical shapes as described herein.
  • the constraint device is configured to provide mechanical support to the membrane when the membrane is filled with a coupling medium/fluid.
  • the constraint device may prevent the membrane of the reservoir or UMC from overexpanding by retaining the constraint device over and around a patient, maintaining acoustic coupling between the transducer and the patient.
  • the constraint device may also minimize any forces applied against a patient and reduce any load transfer to the patient when the reservoir or UMC is filled with the coupling medium/fluid.
  • the membrane constraint 316 of FIGS. 10A is configured to include a portion or section that rests under the patient and is further configured to have one or more portions adapted and configured to attach or be coupled to the coupling assembly, frame body, reservoir or UMC, or operating table.
  • the membrane constraint can comprise a flexible or compliant material.
  • the constraint can be an elastomer such as silicon or rubber or other similar materials.
  • the membrane constraint can have some compliance or elasticity.
  • the membrane constraint should be less flexible or compliant than the coupling membrane (e.g., be stiffer than the membrane).
  • the constraint device 316 can include a central constraint portion or section 322 and one or more peripheral constraint portions or sections 324 extending outward from and/or coupled to the central constraint portion 322.
  • the embodiment of FIG. 10A shows a constraint device 316 with a central constraint portion 322 and a first and second peripheral constraint portion 324 widening from opposite sides of the central constraint portion.
  • the constraint device 316 may define an hour-glass shape and/or the peripheral constrain portions may define trapezoidal a shape. It is envisioned that the constraint device 316 comprises two or more peripheral constraint portions, each peripheral constraint portions being identical in size and shape to one another.
  • one peripheral constraint portion may be larger in size than the other.
  • each peripheral constraint portion may have different shapes, depending on if the patient is right or left facing with respect to the histotripsy system. Combinations of both size and shape for each peripheral constraint portion are also envisioned.
  • FIG. 10B An alternate embodiment is illustrated in Fig 10B, including a one-sided, flanged configuration.
  • the embodiment of FIG. 10B shows a constraint device 416 with a first, patient-contacting portion 422 and a flared portion 424 extending outward from the first, patient-contacting portion 422.
  • the first, patient contacting portion 422 may be configured to include attachment features which attach an exterior portion 422a of the patient-contacting portion 422 to the operating table, C-arm or other mechanically stable structure.
  • exterior portion 422a is able to attach directly to, for example the operating table by attaching the elongated honeycomb structures to an attachment feature found on the operating table.
  • the one-sided flanged portion configuration could be desirable, for example, for particular patients where a treatment area could be accessed easier if only one flanged portion is employed.
  • a one-sided flanged constraint device could also be useful for a side-lying patient or perhaps for a smaller patient. It should be noted that with the exception of the single flanged portion, most other features remain similar to Fig 10A and 10C.
  • the central or patient-contacting portion 322, 422 of the constraint device 316, 416 is configured to be positioned under a patient undergoing a histotripsy or other therapeutic ultrasound procedure.
  • the constraint device can be placed on a medical or operating table, and the patient can then be positioned on top of the patient-contacting portion 322,422.
  • the constraint device 316, 422 may be positioned between the patient and the operating table.
  • the weight of the patient on top of the patient portion is typically sufficient to hold the membrane constraint in place during a histotripsy procedure.
  • the patient-contacting portion 322, 422 can be temporarily or permanently affixed to the medical or operating table as will be described in more detail below.
  • the peripheral constraint portion(s) 324, 424 of the membrane constraint are configured to be attached or coupled to the reservoir or UMC or coupling assembly of the ultrasound therapy system.
  • the coupling assembly 212 (FIG. 2) can include a reservoir or UMC (i.e., a combined membrane and frame body) and a coupling membrane constraint.
  • the reservoir or UMC (and/or coupling assembly) can be filled with an ultrasound coupling medium and placed in contact with the patient’s skin to provide acoustic coupling between a therapy head of the ultrasound system and the patient.
  • the coupling membrane itself can comprise flexible and elastomeric materials, which can result in stretching or expansion of the coupling membrane when the reservoir or UMC is filled with the ultrasound coupling medium.
  • the volume of coupling medium e.g., 10-12L or more
  • the volume of coupling medium within the reservoir or UMC can cause overexpansion of the membrane which can result in coupling medium spillage, an insufficient workspace to allow for movement of the therapy head according to a treatment plan, and/or the inability to properly couple the therapy head with the patient.
  • the peripheral constraint portion(s) 324, 424 of the constraint device 316, 416 can include a plurality of openings 326, 426.
  • the patient portion 322, 422 can also include a plurality of openings 328, 428.
  • the openings 326, 426 of the peripheral constraint portion and openings 328, 428 of the patient portion can comprise a pattern.
  • the pattern of openings in the peripheral constraint portion(s) can be different than the pattern of openings in the patient portion. In other embodiments the patterns of the patient and peripheral constraint portion openings can be the same.
  • the openings in the peripheral constraint portion(s) are configured to engage with, attach to, or interface with the reservoir or UMC via the constraint connectors.
  • the reservoir or UMC may include constraint connectors in the shape or form of hooks, tabs, buttons, or other attachment features which can be connected or attached to the openings of the peripheral constraint portion(s).
  • the pattern of openings 326, 426 in the peripheral constraint portion(s) can comprise a honeycomb pattern or arrangement.
  • the individual openings can include hexagonal shapes. Patterns including shapes which have at least one interior angle may be preferable, such as triangles, squares, rectangles, pentagons, trapezoids, parallelograms, and the like. However, any other shapes can be used for the openings, including circles, ovals, and other shapes including radius of curvature, etc. Combinations of shapes are also envisioned.
  • the openings within the peripheral constraint portion(s) can have different sizes. For example, the honeycomb pattern shown in FIG.
  • the openings within the peripheral constraint portion(s) can have similar or the same sizes throughout the peripheral constraint portion(s).
  • the peripheral portion is optimized for load distribution and support along the coronal plane of the patient.
  • the openings of the peripheral constraint portion include engagement features which can be removably connected to the constraint connectors of the ultrasound coupling assembly.
  • the patient portion 322, 422 can include a different pattern of openings than the openings of the peripheral constraint portion(s).
  • the openings of the peripheral constraint portion(s) are optimized and configured for attachment to constraint connectors of the reservoir or UMC, whereas the openings of the patient portion are typically not attached to the reservoir or UMC.
  • the openings of the patient portion can be optimized and configured to prioritize patient comfort since the patient’s weight is placed on the patient portion and the patient remains laying on the patient portion during the entirety of the histotripsy procedure.
  • the pattern of openings in the patient portion can be configured to reduce hot spots or pressure points.
  • the patient portion may not include any openings but instead may just be a solid or flat portion of the compliant material.
  • an exterior of the patient contacting portion 422a or patient contacting portion 422 may also be configured to attach to the operating table.
  • the exterior patient contacting portion 422a may attach to hooks or other features which extend outward from the operating table to receive an opening in the constraint device 416. More than one opening in the constraint device 416 may be hooked or attached to the table to provide enhanced security.
  • the peripheral constraint portion(s) 324, 424 can have a larger width wl than a width w2 of the patient portion. As shown, the peripheral portions can flare out as they extend away from the patient portion.
  • the peripheral portion(s) may start at a width w2 where they meet or join the patient portion and may flare or extend out to a width wl that is greater than the width w2.
  • this expanding width may be uniform, such that the sides 332 of the peripheral constraint portion(s) maintain a straight edge.
  • sides 332 may be curved or jagged or other shapes that may better facilitate attachment of the constraint to the reservoir or UMC (and/or frame body or coupling assembly).
  • the sides 332 may be curved inwards or outwards to better conform to a patient when the peripheral portion(s) are wrapped around the patient and attached to the reservoir or UMC. In the example of FIG.
  • the peripheral constraint portion(s) 324 may flare out at an angle 329.
  • the angle 329 may be as low as 10-15 degrees and go up to 75-90 degrees. In the illustrated example, the angle 329 can be approximately 20-50 degrees, and preferably about 35 degrees.
  • the uniform flaring of the membrane constraint on each of the peripheral constraint portions of FIG. 10A gives the constraint a shape resembling a bow tie. It is also envisioned that more than one angle 329 or different angles on each peripheral constraint portion can be employed. Alternatively, a smooth transition to the peripheral flare, such as an arc or curve is also envisioned.
  • the constraint device described herein is a monolithic structure.
  • the constraint device may be manufactured from a single sheet of polymer and created using a diecut process.
  • the constraint device may be manufactured using injection molding, or 3D printed.
  • the constraint device may be provided as a transparent or translucent material such that surgical field visibility is optimal.
  • FIG. 11 illustrates one embodiment of a constraint device 1016 coupled to a reservoir or UMC 1013 with a patient 1001 laying on the patient portion 1016a of the constraint device.
  • the constraint connectors 1064 of the reservoir or UMC 1013 are positioned through some of the pores 1026 of the peripheral constraint portion 1024 of the constraint device 1016 to attach (i.e., hang, suspend, connect) the constraint 1016 to the reservoir or UMC 1013.
  • the coupling assembly 1002 of FIG. 11 includes a reservoir or UMC 1013, a membrane 1014, a medium 1005, and a constraint device 1016 thereby coupling the patient acoustically to the histotripsy system and/or treatment.
  • the coupling membrane 1014 is expanded as the reservoir or UMC 1013 has been filled with an ultrasound coupling medium 1005.
  • the flared peripheral portions 1024 of the constraint device 1016 allow for the constraint device 1016 to be attached at various points along the reservoir or UMC 1013 while also maintaining a close fit to the contours of the patient 1001.
  • the patient may be positioned on his or her back, stomach, or side.
  • the flared peripheral portions provide flexibility in how the constraint is attached to the reservoir or UMC, enabling a variety patient positions, treatment head locations, and UMC locations.
  • Membranes and barrier films may be composed of various biocompatible materials which allow conformal coupling to patient anatomy with minimal or no entrapped bubbles capable of interfering with ultrasound imaging and histotripsy therapy, and that are capable of providing a sealed barrier layer between said patient anatomy and the ultrasound medium, of which is contained within the work-space provided by the frame and assembly.
  • Membrane and barrier film materials may comprise flexible and elastomeric biocompatible materials/polymers, such as various thermoplastic and thermoset materials, as well as permanent or bioresorbable polymers. Additionally, the frame of the UMC can also comprise the same materials. In some examples, the membrane may be rigid or semi-rigid polymers which are pre-shaped or flat.
  • the ultrasound medium may comprise any applicable medium capable of providing sufficient and useful acoustic coupling to allow histotripsy treatments and enable sufficient clinical imaging (e.g., ultrasound).
  • Ultrasound mediums as a part of this disclosure and system, may comprise, but are not limited to, various aqueous solutions/mediums, including mixtures with other co-soluble fluids, of which may have preferred or more preferred acoustic qualities, including ability to match speed of sound, etc.
  • Example mediums may comprise degassed water and/or mixtures/co-solutions of degassed water and various alcohols, such as ethanol.
  • Support arms may be configured with a range of degrees of freedom, including but not limited to allowing, x, y, z, pitch, roll and yaw, as well additional interfacing features that may allow additional height adjustment or translation.
  • Arms may comprise a varied number and type of joints and segments. Typically, arms may comprise a minimum of 2 segments. In some configurations, arms may comprise 3 to 5 segments.
  • Arms are also be configured to interface proximally to a main support base or base interface (e.g., robot, table, table/bed rail, cart, floor mount, etc.) and distally to the frame/assembly and overall “UMC” or “coupling solution”.
  • a main support base or base interface e.g., robot, table, table/bed rail, cart, floor mount, etc.
  • This specific distal interface may further include features for controlling position/orientation of the frame/assembly, at the frame/assembly interface.
  • the arm/frame interface may comprise a ball joint wrist.
  • the interface may include use of a gimbal wrist or an adjustable pitch and roll controlled wrist.
  • These interfaces may be further employed with specific user interfaces and inputs, to assist with interacting with the various wrists, of which may include additional handles or knobs (as an unlimited example), to further enable positioning the UMC/coupling solution.
  • a gimbal wrist may benefit from allowing the frame/assembly to have 3 degrees of freedom (independent of the arm degrees of freedom), including pitch, roll and yaw adjustments.
  • Support arms configured with arm wrists, further interfaced with frames/assemblies, may comprise features such as brakes, including cable or electronic actuated brakes, and quick releases, which may interact with one or more axis, individually, or in groupings. They may also include electronic lift systems and base supports. In some embodiments, these lift systems/base supports are co-located with robot arm bases, wherein said robot arm is equipped with the histotripsy therapy transducer configured to fit/work within the enclosed coupling solution. In other embodiments, the support arm is located on a separate cart. In some cases, the separate cart may comprise a fluidics system or user console.
  • a bed/table including but not limited to a rail, side surface, and/or bed/table base.
  • a floor-based structure/footing capable of managing weight and tipping requirements.
  • histotripsy systems including acoustic/patient coupling systems, may be configured to include an automated fluidics system, which primarily is responsible for providing a reservoir for preparation and use of coupling medium.
  • the fluidics system may include the ability to degas, chill, monitor, adjust, dispense/fill, and retrieve/drain coupling medium to/from the coupling frame/assembly.
  • the fluidics system may include an emergency high flow rate system for rapid filling and draining of the coupling medium from the UMC.
  • the fluidics system may be configured to fill the UMC with fluid on demand, or with predetermined fill amounts (e.g., automatic fill of a present volume of fluid such as IL, 3L 6L, 9L, etc.).
  • the fluidics system is configured to connect to or receive fluid from a fluid source such as tap water.
  • the fluidics system can include a degas system or mechanism such as a degas membrane that can be configured to degas fluid as it flows from the fluid source into the fluid tank of the fluidics system.
  • the degas system can be further configured to degas the fluid as it flows from the fluid tank to the UMC.
  • the fluid is degassed to a first degas threshold while the fluid tank is filled from the fluid source, and held at the first degas threshold.
  • the fluidics system can then further degas the fluid as it is transferred from the fluid tank to the UMC (e.g., to a second degas threshold).
  • the fluidics system can be configured for a single use of the coupling medium, or alternatively, for re-use of the medium.
  • the fluidics system can implement positive air pressure or vacuum to carry out leak tests of the UMC and membrane prior to filling with a coupling medium. Vacuum assist can also be used for removal of air from the UMC during the filling process.
  • the fluidics system can further include filters configured to prevent particulate contamination from reaching the UMC.
  • the fluidics system may be implemented in the form of a mobile fluidics cart.
  • the cart may comprise an input tank, drain tank, degassing module, fill pump, drain pump, inert gas tank, air compressor, tubing/connectors/lines, electronic and manual controls systems and input devices, power supplies and one or more batteries.
  • the cart in some cases may also comprise a system check vessel/reservoir for evaluating histotripsy system performance and related system diagnostics (configured to accommodate a required water volume and work-space for a therapy transducer).
  • the cart may be powered through standard electrical service/connectors, as well as with a battery to allow for portable or off-grid use.
  • the battery may also provide emergency power.
  • the cart may also comprise a nitrogen tank and/or air compressor (not shown) for allowing blow down of the main/drain tubing to enable ensuring they are maintained dry/clean (under a nitrogen blanket).
  • the cart may include various processors or electronic controllers configured for programming/monitoring/reporting water status and parameters. Parameters may include oxygen saturation, temperature, particulate debris, pH, mix ratio, flow rate, fill level, power level/battery level, etc., which can be detected in real-time by any number of sensors disposed within and around the system. The parameters may be read out on a UI screen on the fluidics cart, and/or may be displayed/controlled on the therapy system cart display (through software UI).
  • the degassing module may contain filters or degassing membranes configured to remove particulate/debris, a de-gas contactor and a vacuum or peristaltic pump to move fluid through the system.
  • filters may be 0.2 micron in pore size.
  • the de-gas contactor may be able to pull down to parts per billion, with around 3 gallon per minute flow, and capable of removing dissolved O2, CO2 and N2 gas.
  • Vacuum pumps may include key features such as pure transfer and evacuation, high compatibility with vapors and condensation, chemical resistance, and gas tight (very low leakage). In some examples, vacuum pumps are cable of pulling down to 8 torr.
  • the degassing system can omit the pump and can rely on the water source flow rate (e.g., tap water flow rate) to move the fluid through the system.
  • the tubing/connectors/lines, plastic and/or metallic, are configured to allow fluid and air communication through the system and overall acoustic/patient coupling system. These may also contain various components such as valves (e.g., two way, three way, etc.).
  • the electronic and manual controls provide a system and user-facing system controls over all the functions of the system, including but not limited to pump and de-gassing controls.
  • the control systems may further comprise various sensors, in-line and onboard, for sensing temperature, pressure, flow rate, dissolved oxygen concentration, volume, etc.
  • the fluidics system and cart may also have various electrical connections for power including leveraging external power, and/or may comprise a battery/toroid for enabling a detethered fully mobile configuration. This allows the fluidics cart to be wheeled up to prepare/set up a histotripsy procedure, and then wheel away once all fluidics related work-flow steps are complete, so as to not require the fluidics cart to be patient side during treatment/therapy .
  • the fluidics cart architecture and design may also include handles, individual or central locking casters, a top work surface, embedded user display devices, connectivity (e.g., ethemet, etc.), and may be designed to allow further integration of the support arm in some embodiments. It may also be outfitted with long/extended tubing to support intra-imaging system filling/draining, if for example, use within a CT or MRI, is desirable, so as to not have the overall medium/water volume in close proximity to the scanner, and/or filling during set up is required to further assess image/body divergence pre/post filling.
  • intra-imaging system filling/draining if for example, use within a CT or MRI, is desirable, so as to not have the overall medium/water volume in close proximity to the scanner, and/or filling during set up is required to further assess image/body divergence pre/post filling.

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  • Biomedical Technology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
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Abstract

L'invention concerne un système de thérapie par histotripsie conçu pour le traitement d'un tissu, qui peut comprendre n'importe quel nombre de caractéristiques. L'invention concerne des systèmes et des procédés qui fournissent des procédures thérapeutiques, diagnostiques et de recherche efficaces non invasives et minimalement invasives. Des modes de réalisation supplémentaires de la présente invention concernent des systèmes de couplage pour l'histotripsie comprenant divers réservoirs ou contenants de milieu ultrasonore (UMC) et des contraintes de couplage conçues pour interfacer avec un réservoir ou un UMC pendant une procédure d'histotripsie.
PCT/US2023/083452 2023-08-11 2023-12-11 Systèmes de couplage ultrasonore pour histotripsie et systèmes, procédés et dispositifs associés Pending WO2025038127A1 (fr)

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US12390665B1 (en) 2022-10-28 2025-08-19 Histosonics, Inc. Histotripsy systems and methods
US12446905B2 (en) 2023-04-20 2025-10-21 Histosonics, Inc. Histotripsy systems and associated methods including user interfaces and workflows for treatment planning and therapy

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US20200164231A1 (en) * 2018-11-28 2020-05-28 Histosonics, Inc. Histotripsy systems and methods
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US10010722B2 (en) * 2009-09-29 2018-07-03 Liposonix, Inc. Transducer cartridge for an ultrasound therapy head
US11304676B2 (en) * 2015-01-23 2022-04-19 The University Of North Carolina At Chapel Hill Apparatuses, systems, and methods for preclinical ultrasound imaging of subjects
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US12390665B1 (en) 2022-10-28 2025-08-19 Histosonics, Inc. Histotripsy systems and methods
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