Planning tools and software interfaces for generating and guiding histotrypsy treatment plans and therapies.

Abstract

A histotripsy treatment system configured for tissue therapy is provided. This system can incorporate any number of functions. This specification provides systems and methods that offer effective non-invasive and minimally invasive treatment, diagnostic, and research procedures. A treatment planning tool is provided that can simulate treatment, allowing the user to identify preferred orientations or positions of the histotripsy treatment transducer array for a specific treatment site. This planning tool can identify faulty transducer elements in a specific orientation / position and provide pressure simulations to estimate the driving voltage required to generate cavitation at the treatment site. Selections or modifications to the treatment plan made with the planning tool can be transferred to the histotripsy system for use during the treatment procedure.

Description

Technical Field

[0001] <Priority Claim> This patent application claims priority to U.S. Provisional Patent Application No. 63 / 583,086, filed on September 15, 2023, entitled "HISTOTRIPSY SYSTEMS AND METHODS", which is hereby incorporated by reference in its entirety into the present specification.

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

[0003] The present disclosure details novel high-intensity therapeutic ultrasound (HITU) systems configured to generate acoustic cavitation, as well as methods, apparatuses, and procedures for minimally and non-invasively treating healthy, diseased, or damaged tissue. The acoustic cavitation systems and methods described in the present specification, also referred to as histotripsy (ultrasound tissue destruction therapy), include transducers, drive electronics, positioning robots, imaging systems, and integrated treatment planning and control software to provide comprehensive therapy and treatment for soft tissues of a patient.

Background Art

[0004] Histotripsy, or pulsed ultrasound cavitation therapy, is a technique that induces controlled cavitation (formation of microbubbles) within a focal volume by means of extremely short, intense bursts of acoustic energy. The violent expansion and contraction of these microbubbles mechanically homogenize cells and tissue structures within the focal volume. This is a completely different end result from the coagulative necrosis characteristic of thermal ablation. To operate in a non-thermal tissue destruction region, acoustic energy must be supplied in the form of high-amplitude acoustic pulses with a low duty cycle.

[0005] Compared to conventional focused ultrasound techniques, histotripsy offers significant advantages: 1) the destructive process at the focal point is mechanical rather than thermal; 2) cavitation appears bright on the ultrasound image, confirming correct targeting and localization of treatment; 3) treated tissue generally (but not always) appears dark (hypoechoic) on the ultrasound image, allowing the operator to identify the treated area; 4) histotripsy generates lesions in a controlled and precise manner. Unlike thermal ablation techniques such as microwave, radiofrequency, high-intensity focused ultrasound (HIFU), cryotherapy, and radiation, histotripsy relies on the mechanical action of cavitation for tissue destruction, rather than heat, cold, or ionizing energy. [Overview of the project]

[0006] A method for planning tissue ablation therapy is provided. The method comprises: acquiring at least one diagnostic image of an object including the location of the target tissue; generating a three-dimensional (3D) digital model of the subject and the location of the target tissue from at least one diagnostic image; positioning a virtual tissue ablation therapy transducer array near the 3D model so that the geometric focus of the virtual tissue ablation therapy transducer is located on or near the location of the target tissue in the 3D digital model; sampling the virtual tissue ablation therapy transducer array to provide starting points for multiple rays corresponding to the simulated ultrasonic energy supplied by the transducer elements of the virtual tissue ablation therapy transducer; tracking the multiple rays through the 3D digital model; and identifying one or more obstructions or partially damaged transducer elements of the virtual tissue ablation therapy transducer array corresponding to rays passing through obstacles in the 3D digital model.

[0007] In one embodiment, the method further includes the step of displaying to the user a ray of light passing through an obstacle.

[0008] In some embodiments, the method includes the steps of providing a first graphical representation of a ray passing through an obstacle and a second graphical representation of a ray not passing through an obstacle.

[0009] In one embodiment, light rays passing through an obstacle are represented in the first color, and light rays not passing through the obstacle are represented in the second color.

[0010] In one embodiment, the 3D digital model further includes a skin surface model of the subject.

[0011] In some embodiments, this method includes displaying a map of light rays passing through obstacles on a skin surface model.

[0012] In some embodiments, displaying light rays passing through an obstacle further includes providing a two-dimensional view of multiple light rays.

[0013] In another embodiment, the method further includes: receiving input to adjust the position or orientation of the virtual tissue ablative therapy transducer; resampling the virtual tissue ablative therapy transducer array to provide starting points for a second set of rays corresponding to the simulated ultrasonic energy supplied by the transducer elements of the virtual tissue ablative therapy transducer array; tracking the second set of rays through a 3D digital model; and identifying one or more obstructed or partially obstructed transducer elements of the virtual tissue ablative therapy transducer array corresponding to rays passing through obstacles in the 3D digital model.

[0014] In some embodiments, the method further includes generating a digital treatment plan that includes the location of the target tissue and the orientation or position of the virtual tissue-disrupting therapy transducer array.

[0015] In one embodiment, the digital treatment plan further includes the depth and size of the target tissue location.

[0016] In another embodiment, the method includes dividing one or more target tissues or organs located near the location of the target tissue.

[0017] A method for planning histotripsy therapy is provided. This method includes: acquiring at least one diagnostic image including the target tissue location of the object; generating a three-dimensional (3D) digital model of the object and target tissue location from at least one diagnostic image; positioning a virtual tissue ablation transducer array near the object so that the geometric focus of the tissue ablation transducer is located on or near the target tissue location; sampling the virtual tissue ablation transducer array to provide the starting points of multiple rays corresponding to the ultrasonic energy supplied by the transducer elements of the tissue ablation transducer array; tracking multiple rays passing through the tissue boundary in the 3D digital model; and identifying the refraction angles of one or more rays passing through the tissue boundary from a first sound-speed medium into a second sound-speed medium.

[0018] In another embodiment, this method includes showing the angle of refraction of the light ray to the user.

[0019] In one embodiment, this method includes displaying the angle of refraction of a ray to the user.

[0020] In some embodiments, this method includes displaying the expected focal point of a ray based on the angle of refraction.

[0021] In other embodiments, this method includes displaying a model of the subject's skin surface, which includes a map of light rays affected by the angle of refraction.

[0022] In one embodiment, this method includes the step of providing a two-dimensional view of a ray.

[0023] In some embodiments, this method includes dividing the path length of each ray into a plurality of segments having known sound velocities.

[0024] In another aspect, the method includes calculating a time delay for each light ray to reach the geometric focal point.

[0025] In some embodiments, the method includes adjusting the timing of ultrasonic irradiation for a plurality of transducer elements of a tissue ablation therapy transducer based on the calculated time delay.

[0026] A method for planning histotripsy therapy, comprising: acquiring at least one diagnostic image including a target tissue location of a subject; generating a three-dimensional (3D) digital model of the subject and the target tissue location from the at least one diagnostic image; positioning a virtual tissue ablation therapy transducer array proximate to the subject such that the geometric focal point of the tissue ablation therapy transducer array is located at or near the location of the target tissue; sampling the tissue ablation therapy transducer to provide starting points for a plurality of light rays corresponding to the ultrasonic energy delivered by the transducer elements of the tissue ablation therapy transducer array; tracing the plurality of light rays through the 3D digital model; generating a pressure simulation within the 3D digital model based on the plurality of light rays; and estimating, based on the pressure simulation, one or more drive voltages of the virtual tissue ablation therapy transducer array required to generate cavitation at the target tissue site.

[0027] In some embodiments, generating the pressure simulation further comprises calculating a Rayleigh-Sommerfeld integral over a 2D or 3D calculation domain.

[0028] In one embodiment, the method includes displaying to a user the light rays that pass through an obstacle.

[0029] In another embodiment, the method includes providing a first graphical representation of light rays that pass through the obstacle and a second graphical representation of light rays that do not pass through the obstacle.

[0030] In one embodiment, light rays passing through an obstacle are displayed in the first color, and light rays not passing through the obstacle are displayed in the second color.

[0031] In one respect, the 3D digital model further includes a model of the subject's skin surface.

[0032] In another embodiment, this method includes displaying a map of light rays passing through obstacles on a skin surface model.

[0033] In one embodiment, displaying light rays passing through an obstacle further includes providing a two-dimensional view of multiple light rays.

[0034] In another embodiment, the method includes: receiving input to adjust the position or orientation of a virtual tissue ablative therapy transducer; resampling the virtual tissue ablative therapy transducer array to provide starting points for a second set of rays corresponding to the simulated ultrasonic energy supplied by the transducer elements of the virtual tissue ablative therapy transducer array; tracking the second set of rays through a 3D digital model; and identifying one or more obstructed or partially obstructed transducer elements of the virtual tissue ablative therapy transducer array corresponding to rays passing through obstacles in the 3D digital model.

[0035] In some embodiments, this method includes generating a digital treatment plan that includes the location of the target tissue and the orientation or position of a virtual tissue-disrupting therapy transducer array.

[0036] In another embodiment, the digital treatment plan further includes the depth and size of the target tissue location.

[0037] In some embodiments, the method includes dividing one or more target tissues or organs located near the location of the target tissue.

[0038] An ultrasound system is provided. The system comprises the following components: a robotic positioning system; an ultrasound transducer array positioned on the robotic positioning system, the ultrasound transducer array configured to irradiate an object with ultrasound pulses; a diagnostic imaging system configured to acquire preoperative images of a subject; a display; one or more processors operably connected to the robotic positioning system, the diagnostic imaging system, the ultrasound transducer array, and the display; and a readable medium for a non-transient computing device storing instructions for generating a treatment plan for ultrasound therapy. The aforementioned instructions are executed by one or more processors, causing the ultrasound system to perform the following actions: acquire at least one diagnostic image including the location of the target tissue using a diagnostic imaging system; generate a three-dimensional (3D) digital model of the target tissue and its location from at least one diagnostic image; position the ultrasound transducer array near the subject so that the geometric focus of the tissue ablative therapy transducer is located on or near the location of the target tissue; sample the ultrasound transducer array to provide starting points for multiple rays corresponding to the ultrasound energy supplied by the transducer elements of the ultrasound transducer array; trace the multiple rays through the 3D digital model; identify one or more occluding rays corresponding to rays passing through obstacles in the object; and display the multiple rays and one or more occluding rays superimposed on the 3D digital model on a display.

[0039] In one embodiment, blocked light rays are displayed in the first color, and unblocked light rays are displayed in the second color.

[0040] In another embodiment, instructions are executed by one or more processors, causing the ultrasound system to display a 3D model of the subject's skin surface, including a map of blocked rays.

[0041] In one embodiment, instructions are executed by one or more processors to provide a two-dimensional view of light rays shielded by an ultrasonic system.

[0042] A tissue destruction treatment planning tool is also provided. The tool comprises: a display; a user interface; one or more processors operablely connected to the display and user interface; and a readable medium for a non-temporary computing device containing instructions for generating an ultrasound treatment plan. The instructions are executed by one or more processors and perform the following: receive one or more diagnostic images including the target tissue location of the object; display a three-dimensional (3D) model of the object and target tissue location on the display and display a virtual ultrasound treatment transducer array near the 3D model of the object; receive input from the user interface, including instructions for changing the orientation or position of the virtual ultrasound treatment transducer array; simulate multiple rays from the virtual ultrasound treatment transducer array toward the 3D model of the subject and the target tissue location at a specific orientation and position; and display information on the display indicating whether any of the multiple rays will pass through an obstacle in the 3D model of the object. [Brief explanation of the drawing]

[0043] The novel features of the present invention are specifically described in the following claims. For a better understanding of the features and advantages of the present invention, please refer to the following detailed description, which includes exemplary embodiments in which the principles of the present invention are utilized, and to the accompanying drawings.

[0044] [Figure 1A] This shows an ultrasound imaging and treatment system. [Figure 1B] This shows an ultrasound imaging and treatment system.

[0045] [Figure 2] This document describes one embodiment of a tissue disruption therapy and imaging system equipped with a binding system.

[0046] [Figure 3] This is an example of an ultrasonic pulse used to generate tissue destruction via a shock scattering mechanism.

[0047] [Figure 4A] This shows the user interface workflow screen of the treatment planning tool. [Figure 4B] This shows the user interface workflow screen of the treatment planning tool. [Figure 4C] This shows the user interface workflow screen of the treatment planning tool. [Figure 4D] This shows the user interface workflow screen of the treatment planning tool. [Figure 4E] This shows the user interface workflow screen of the treatment planning tool. [Figure 4F] This shows the user interface workflow screen of the treatment planning tool. [Figure 4G] This shows the user interface workflow screen of the treatment planning tool. [Figure 4H] This shows the user interface workflow screen of the treatment planning tool. [Figure 4I] This shows the user interface workflow screen of the treatment planning tool. [Figure 4J] This shows the user interface workflow screen of the treatment planning tool. [Figure 4K] This shows the user interface workflow screen of the treatment planning tool. [Figure 4L] This shows the user interface workflow screen of the treatment planning tool. [Figure 4M] This shows the user interface workflow screen of the treatment planning tool. [Figure 5] This shows the user interface workflow screen of the treatment planning tool.

[0048] [Figure 6A]This example demonstrates the use of ray tracing in a histotripsy treatment system to identify potential obstacles between the treatment transducer and the focus. [Figure 6B] This example demonstrates the use of ray tracing in a histotripsy treatment system to identify potential obstacles between the treatment transducer and the focus.

[0049] [Figure 7A] This is an example of a treatment planning tool that uses ray tracing to provide users with information about potential obstacles and optimal transducer placement. [Figure 7B] This is an example of a treatment planning tool that uses ray tracing to provide users with information about potential obstacles and optimal transducer placement. [Figure 7C] This is an example of a treatment planning tool that uses ray tracing to provide users with information about potential obstacles and optimal transducer placement. [Figure 7D] This is an example of a treatment planning tool that uses ray tracing to provide users with information about potential obstacles and optimal transducer placement. [Figure 7E] This is an example of a treatment planning tool that uses ray tracing to provide users with information about potential obstacles and optimal transducer placement. [Figure 7F] This is an example of a treatment planning tool that uses ray tracing to provide users with information about potential obstacles and optimal transducer placement. [Figure 7G] This is an example of a treatment planning tool that uses ray tracing to provide users with information about potential obstacles and optimal transducer placement.

[0050] [Figure 8A] This presents a treatment planning tool that provides users with information on potential obstacles, optimal transducer placement, and potential collisions between transducers, coupling containers, and / or patients. [Figure 8B] This presents a treatment planning tool that provides users with information on potential obstacles, optimal transducer placement, and potential collisions between transducers, coupling containers, and / or patients. [Figure 8C] This presents a treatment planning tool that provides users with information on potential obstacles, optimal transducer placement, and potential collisions between transducers, coupling containers, and / or patients. [Figure 8D] This presents a treatment planning tool that provides users with information on potential obstacles, optimal transducer placement, and potential collisions between transducers, coupling containers, and / or patients. [Figure 8E] This presents a treatment planning tool that provides users with information on potential obstacles, optimal transducer placement, and potential collisions between transducers, coupling containers, and / or patients. [Figure 8F] This presents a treatment planning tool that provides users with information on potential obstacles, optimal transducer placement, and potential collisions between transducers, coupling containers, and / or patients. [Modes for carrying out the invention]

[0051] The systems, methods, and apparatus of this disclosure can be used in open surgery, minimally invasive surgery (laparoscopic and percutaneous surgery), robotic surgery (integrated into robot-enabled medical systems), endoscopic surgery, or complete percutaneous extracorporeal non-invasive acoustic cavitation for the treatment of healthy tissue, diseased tissue, and / or damaged tissue, including but not limited to tissue destruction, cutting, skeletalization, and ablation. Furthermore, due to its tissue-selective properties, tissue destruction can potentially be used to form a cytoskeleton that enables subsequent tissue regeneration, which may be novel or achieved through the application of stem cells or other adjuvants. Finally, histotripsy can be used to promote the release of administered drugs, such as chemotherapeutic agents and immunotherapeutic agents, by irradiating a target site with acoustic energy to induce local release of these drugs. As described later, the acoustic cavitation system may include a variety of subsystems, such as carts, treatment devices, integrated imaging devices, robotic devices, coupling devices, and software. This system may include, but is not limited to, computers, cables and connectors, network equipment, power supplies, displays, drawers / storage units, doors, wheels, and various simulation and training tools, as well as other various components, auxiliary devices, and accessories. All systems, methods, and means for generating / controlling / performing tissue destruction therapy, including novel related inventions disclosed herein, are considered part of this disclosure.

[0052] Figure 1A shows a schematic diagram of the tissue destruction system 100 according to this disclosure, comprising a therapeutic transducer 102, an imaging system 104, a display and control panel 106, a robotic positioning arm 108, and a cart 110. The system may further include an ultrasonic coupling interface and a coupling medium source, which are not shown.

[0053] Figure 1B is a bottom view of the therapeutic transducer 102 and the imaging system 104. As shown, the imaging system can be positioned in the center of the therapeutic transducer. However, in other embodiments, the imaging system can be positioned elsewhere within the therapeutic transducer or directly integrated with the therapeutic transducer. In some embodiments, the imaging system is configured to generate real-time imaging at the focus of the therapeutic transducer. In this system, by positioning multiple image transducers within the therapeutic transducer, it is also possible to simultaneously acquire multiple viewpoints of the target tissue and integrate these images to create a single 3D image.

[0054] The histotripsy system comprises a therapeutic subsystem capable of generating, applying, concentrating, and delivering acoustic cavitation / historupsy via one or more therapeutic transducers; an integrated imaging subsystem (or connection) capable of real-time visualization of the treatment site and histotripsy effect throughout the procedure; a robotic positioning subsystem for mechanically and / or electronically maneuvering the therapeutic transducers (and further configurable to connect to / support or interact with a coupling subsystem enabling acoustic coupling between the therapeutic transducer and the patient); software for communicating, controlling, and interfaceing with the system and computer-based control systems (and other external systems); and various other components, auxiliary devices, and accessories, including one or more user interfaces and displays, associated guided workflows, all operating partially or in conjunction. The system may further comprise various fluid control and fluid management components, including, but not limited to, pumps, valves and flow control devices, temperature and degassing control devices, irrigation and suction functions, and fluid supply and storage functions. It may also comprise various power supplies and protective devices.

[0055] As described above, the tissue destruction system may have integrated imaging capabilities. However, in other embodiments, the tissue destruction system may be configured to connect to a separate imaging system such as a C-arm, fluoroscopy unit, cone-beam CT, or MRI to provide real-time imaging during tissue destruction therapy. In some embodiments, the tissue destruction system may be sized and configured to fit a C-arm, fluoroscopy unit, cone-beam CT, MRI, etc.

[0056] cart Cart 110 can be configured in various ways and shapes depending on the application and procedure. In some cases, the system may consist of multiple carts configured in similar or different configurations. In some embodiments, the cart is configured and positioned for use in a radiology environment and may be used in conjunction with diagnostic imaging (e.g., CT, cone-beam CT, and / or MRI scans). In other embodiments, it may be configured for use in operating rooms and sterile environments for open surgery, laparoscopic surgery, and endoscopic surgery, or for use in robot-assisted operating rooms, and may be used alone or as part of a surgical robot procedure in which a surgical robot performs specific tasks before, during, or after the use of the system, and performs acoustic cavitation / tissue destruction. Therefore, depending on the treatment environment based on the embodiments described above, the cart may be positioned to provide sufficient workspace and access to various anatomical parts of the patient (e.g., torso, abdomen, flank, head and neck, etc.) as well as workspace for other systems (e.g., anesthesia cart, laparoscopy tower, surgical robot, endoscopy tower, etc.).

[0057] The cart operates in conjunction with the patient's surface (e.g., a table or bed), allowing the patient to be presented and repositioned in various positions, angles, and orientations, and these changes can be made before, during, and after the procedure. Furthermore, it may be capable of interfaceing and communicating with one or more external imaging or image data management and communication systems of one or more modalities, such as ultrasound, CT, fluoroscopy, cone-beam CT, PET, PET / CT, MRI, optics, ultrasound, image fusion, and / or image flow, supporting usage procedures and / or environments including physical / mechanical interoperability (e.g., compatibility within a cone-beam CT workspace for collecting imaging data before, during, and / or after tissue ablative surgery), and providing access to and display of patient medical data, including but not limited to examination data and historical medical record data.

[0058] In some embodiments, one or more carts may be configured to operate in conjunction with each other. For example, one cart may consist of a bedside mobile cart equipped with one or more robotic arms, such as therapeutic transducers and therapeutic generators / amplifiers, while another cart may operate in conjunction with the other cart at a location away from the patient and may have a console / display for controlling integrated imaging and robotic and therapeutic functions, similar to a master / slave configuration with a surgical robot.

[0059] In some embodiments, the system may comprise multiple carts, all dependent on a single master cart, equipped to perform acoustic cavitation procedures. Depending on the configuration, some cart configurations may reduce operating room congestion by storing certain subsystems in separate locations, while others may house almost all bedside subsystems and components (e.g., delivery systems and treatment equipment).

[0060] There are countless possible combinations and configurations for the cart design, and these examples do not in any way limit the scope of disclosure.

[0061] Histotripsy Histotripsy uses short, high-amplitude focused ultrasound pulses to generate a high-density, high-energy "bubble cloud," enabling fragmentation and destruction of targeted tissue. When applied to tissue interfaces (including tissue / fluid interfaces), histotripsy can cause controlled tissue erosion, and when applied to whole tissues, it can perform clearly distinguished tissue fragmentation and destruction at the subcellular level. Unlike other ablation methods using heat or radiation, histotripsy does not require heat, cold, or ionizing (high) energy to treat tissue. Instead, histotripsy utilizes acoustic cavitation generated at the focal point to mechanically affect tissue structure, potentially liquefying, suspending, dissolving, and / or destroying tissue down to its subcellular components.

[0062] Histotripsy can be applied in various forms, including: 1) Intrinsic threshold histotripsy: Typically, a 1-2 cycle pulse of high amplitude negative / tensile phase pressure exceeding the intrinsic threshold for cavitation in the medium is applied (e.g., approximately 24-28 MPa for aqueous soft tissue). 2) Shock scattering histotripsy: Typically, a pulse of 1-20 cycles is applied. The shock waves (positive / compression phase) scattered from the initially generated individual microbubbles form inverted shock waves, which constructively interfere with the incident negative / tensile phase to form a high amplitude negative / dilute phase exceeding the intrinsic threshold. In this way, clusters of cavitating microbubbles are generated. The amplitude of the tensile phase of the pulse is sufficient for bubble nuclei in the medium to undergo inertial cavitation within the focal region throughout the pulse duration. These nuclei scatter the incident shock wave, invert and constructively interfere with the incident wave, exceeding the threshold for intrinsic nucleation. 3) Boiling histotripsy: A pulse of approximately 1-20 milliseconds is used. The absorption of the shock pulse rapidly heats the medium, thereby lowering the threshold of the intrinsic nucleus. When this intrinsic threshold coincides with the maximum negative pressure of the incident wave, a boiling bubble forms at the focus.

[0063] The high pressure generated at the focal point, exceeding a certain threshold, forms a cloud of acoustic cavitation bubbles, causing localized stress and strain in the tissue, leading to mechanical failure without significant heat accumulation. At pressure levels where cavitation does not occur, the impact on the tissue at the focal point is minimal. This cavitation effect is observed only at pressure levels significantly higher than those defining the inertial cavitation threshold in water for similar pulse durations, i.e., on the order of peak negative pressure of 10–30 MPa.

[0064] Tissue ablative therapy can be performed in various ways and with different parameters. It can be performed completely non-invasively by acoustically coupling a focused ultrasound transducer to the patient's skin and percutaneously transmitting acoustic pulses through the overlying (and intervening) tissue to the focal area (treatment area and site). The application of tissue ablative therapy is not limited to percutaneous approaches, but can be applied by any means that allows contact between the transducer and tissue, such as open surgery, laparoscopic surgery, percutaneous surgery, and robot-assisted surgery. The bubble cloud generated by tissue ablative therapy can be visualized as a highly dynamic and hyperechoic area on, for example, B-mode ultrasound images, so direct visualization using ultrasound images allows for further targeting, planning, direction, and observation, thereby enabling continuous visualization throughout tissue ablative therapy (and associated procedures). Similarly, treated and fractionated irradiated tissues show dynamic changes in echogenicity (usually a decrease), which can be used for treatment evaluation, planning, observation, and monitoring.

[0065] Generally, in tissue destruction therapy, ultrasound pulses with one or more acoustic cycles are applied, and the formation of a bubble cloud depends on the pressure-releasing scattering of the positive shock wavefront (which can exceed 100 MPa, P+) from the initially formed, sparsely distributed bubbles (or a single bubble). This is called the "shock scattering mechanism."

[0066] Figure 3 shows an ultrasonic pulse that can be used for shock scattering histotripsy. As illustrated, the ultrasonic pulse can include a preceding negative half-cycle, a peak positive half-cycle, a peak negative half-cycle, and a succeeding peak positive half-cycle (the pulse moves from right to left on the plane of the paper). As shown in the figure, the succeeding positive peak cycle has a smaller amplitude than the positive peak cycle. This mechanism relies on one (or a few sparsely distributed) bubbles generated in the first negative half-cycle of the pulse at the transducer's focus. The high-amplitude positive shock wavefronts resulting from these sparsely generated bubbles are then backscattered by pressure release, forming a cloud of microbubbles. These backscattered high-amplitude rarefied waves exceed an intrinsic threshold, generating locally dense bubble clouds. Each subsequent acoustic cycle, if its amplitude is sufficient, further cavitation is caused by backscattering from the surface of the bubble cloud, increasing its amplitude toward the transducer. As a result, a long, dense bubble cloud is observed that grows along the acoustic axis opposite to the direction of ultrasound propagation due to the shock scattering mechanism. This shock wave scattering process makes the generation of the bubble cloud dependent not only on the maximum negative pressure but also on the number of acoustic cycles and the amplitude of the positive shock wave. Unless at least one strong shock wavefront is generated by nonlinear propagation, a dense bubble cloud will not be generated if the negative half-period peak is below the intrinsic threshold.

[0067] If the amplitude of the positive half-period of each pulse is limited, shock scattering can be minimized, and the formation of a dense bubble cloud depends on the negative half-period of the applied ultrasonic pulse exceeding the "intrinsic threshold" of the medium. This is called the "intrinsic threshold mechanism."

[0068] This threshold ranges from 26 to 30 MPa for soft tissues with high water content, such as human tissue. In some embodiments, this inherent threshold mechanism can be used to clearly define and make more predictable the spatial extent of lesions. If the maximum negative pressure (P-) does not significantly exceed this threshold, reproducible lesions sub-wavelength, approximately half the transducer's -6 dB beamwidth, may be generated.

[0069] High-frequency histotripsy pulses are advantageous for applications requiring precise lesion generation because they result in a smaller minimum reproducible lesion size. However, high-frequency pulses are susceptible to attenuation and aberrations, posing problems for treatments involving deeper penetration depths (e.g., deep tissue ablation) or through highly aberrated media (e.g., transcranial procedures or procedures where pulses are transmitted through bone). Tissue ablation can also be applied using a combination of low-frequency "pump" pulses (typically less than two cycles, with frequencies between 100 kHz and 1 MHz) and high-frequency "probe" pulses (typically less than two cycles, with frequencies above 2 MHz, or between 2 MHz and 10 MHz). In this case, the peak negative pressures of the low-frequency and high-frequency pulses constructively interfere, exceeding the intrinsic threshold of the target tissue or medium. Low-frequency pulses, which are resistant to attenuation and aberrations, can increase the peak level of negative pressure P- in the region of interest (ROI), while high-frequency pulses, which offer higher precision, can accurately pinpoint the target location within the ROI and raise the negative pressure P- peak above an intrinsic threshold. This technique is sometimes called "dual-frequency," "dual-beam tissue ablation," or "parametric tissue ablation."

[0070] Additional systems, methods, and parameters that achieve optimized tissue destruction using various parameters enabling impact scattering, intrinsic thresholds, frequency synthesis, and bubble manipulation are included as part of the systems and methods disclosed herein, and also include additional means for controlling the tissue destruction effect relating to focus manipulation and positioning, and means for simultaneously managing tissue effects within the treatment site or intervening tissue (e.g., pre-focal thermal secondary damage). Furthermore, various systems and methods that may include multiple parameters, such as frequency, operating frequency, center frequency, pulse repetition frequency, pulse, burst, number of pulses, cycle, pulse length, pulse amplitude, pulse period, delay, burst repetition frequency, the aforementioned sets, loops of multiple sets, loops of multiple and / or different sets, sets of loops, and various combinations and permutations thereof, are disclosed as part of this disclosure, including future embodiments.

[0071] Therapeutic components The therapeutic subsystem can work in conjunction with other subsystems to generate, optimize, irradiate, visualize, monitor, and control acoustic cavitation (also referred to herein and hereafter as “tissue disruption”) and its derivatives (including boiling tissue disruption and other thermal high-frequency ultrasonic approaches). It should be noted that the disclosed invention may also be beneficial to other acoustic therapies that do not involve cavitation, mechanical elements, or tissue disruption elements. This therapeutic subsystem may, among other things, include an ultrasonic therapeutic transducer and a pulse generator system configured to irradiate tissue with ultrasonic pulses.

[0072] To generate and provide tissue abrasion therapies and derivatives thereof, the therapeutic subsystem may comprise one or more components including, but not limited to, function generators, amplifiers, therapeutic transducers, power supplies, and the like.

[0073] Therapeutic transducers consist of one or more elements and are configured to be excited by high-amplitude electrical pulses (1000V or more, or other voltages that may be harmful to living organisms). The amplitude required to drive a therapeutic transducer for tissue ablation therapy varies depending on the transducer design and the materials used (e.g., solid or polymer / piezoelectric composite materials (including ceramic or single crystal)), and the center frequency of the transducer is directly proportional to the thickness of the piezoelectric material. Therefore, a transducer operating at high frequencies can generate a given surface pressure at a lower voltage than a transducer for low-frequency therapeutics. In some embodiments, the transducer elements are formed using piezoelectric polymer composite materials or solid piezoelectric materials. Furthermore, the piezoelectric material may be polycrystalline / ceramic or single crystal. In some embodiments, the transducer elements can be formed from silicon using MEMS technology, including CMUT and PMUT designs.

[0074] In some embodiments, the function generator may comprise a field-programmable gate array (FPGA) or other suitable function generator. The FPGA may be configured with the parameters disclosed herein, which include, but are not limited to, frequency, pulse repetition frequency, burst, number of bursts (a burst includes pulses, number of pulses, pulse length, pulse period, delay, burst repetition frequency or period), a set of bursts constituting a parameter set, a loop set including various parameter sets with or without delay, or various delays, and / or multiple loop sets that are independently controlled by various time delays and / or new loop sets introduced, in various combinations and permutations thereof.

[0075] In some embodiments, the generator or amplifier is configured as a general-purpose single-cycle or multi-cycle pulse generator, supporting Class D or inductive drive and accommodating all conceivable clinical applications and operating environments, which are also partially described later in this disclosure. In other embodiments, the Class D or inductive current driver may be configured to include a transformer and / or autotransformer drive circuit to further provide a boost / buck component, which may, in some cases, preferably allow for amplitude boosting. The system may also be provided with certain protective features that further support the system and protect the system (e.g., therapeutic transducer and amplifier circuit components) and the user from a variety of hazards, including but not limited to electrical safety hazards, that could cause harm, injury, or problems to the operating environment, the system, the therapeutic system, and the user.

[0076] The disclosed generator enables and supports the system's ability to select, modify, and control various parameters (via activated software tools). This includes, but is not limited to, previously disclosed, setting and reading of treatment initiation / stopping, voltage level, pulse and / or burst repetition frequency, cycle count, duty cycle, channel activation and delay, modulation of pulse amplitude on a fast time scale independent of the high-voltage power supply, and / or other service, diagnostic, or therapeutic functions.

[0077] In some embodiments, the therapeutic subsystem and / or its components (e.g., amplifiers) may further feature integrated computer processing capabilities, be network-connected, connectable, accessible, and / or removable / portable, modular, and / or interchangeable between systems, and / or driven / controlled by / by other systems, or allow for various combinations. Other systems may include acoustic cavitation / tissue destruction, HIFU, HITU, radiotherapy, radiofrequency, microwave, cryoablation systems, navigation and localization systems, open surgery, laparoscopic surgery, single-incision / single-port surgery, endoscopic surgery, non-invasive surgical robots, and other energy-based or vision systems, including laparoscopes or surgical towers, surgical system racks or booms, imaging carts, etc.

[0078] In some embodiments, one or more amplifiers may comprise a Class D amplifier and associated drive circuitry including matching network components. By actively setting the combined impedance low, depending on the electrical impedance of the transducer element and the selection of matching circuitry components (e.g., an LC circuit with inductors L1 in series and capacitors C1 in parallel), the high-amplitude electrical waveform required to drive the transducer element can be obtained. The maximum amplitude of the Class D amplifier depends on the circuitry components used, such as drive MOSFET / IGBT transistors, matching circuitry components or inductors, transformers or autotransformers, and is typically in the low kV range (e.g., 1-3 kV).

[0079] Therapeutic transducer elements are excited by an electrical waveform with an amplitude (voltage) sufficient to generate a pressure output for histotripsy treatment. The excitation field can be defined as the required waveform voltage per unit thickness of the piezoelectric element. For example, a piezoelectric element operating at a frequency of 1 MHz is half the thickness of an equivalent 500 kHz element, so half the voltage is required to obtain the same electric field and surface pressure.

[0080] The therapeutic subsystem may also include therapeutic transducers with various designs and operating parameters to support use in a variety of procedures (and procedure configurations). The system consists of one or more therapeutic transducers, which are further interchangeable and interact with various aspects of the system in similar or different ways (for example, they may connect to a robotic arm using a common interface and interchangeability, or conversely, adapt to interact with application-specific imaging probes in different ways, or different imaging probes may interact and integrate with therapeutic transducers in specifically different ways).

[0081] Therapeutic transducers may consist of various parameters such as size, shape (e.g., rectangular or circular, anatomically curved housing), geometric shape, focal length, number of elements, size of elements, distribution of elements (e.g., number of rings, size of rings in annular-patterned transducers), frequency, and electron beam steering activation. Transducers may also consist of various materials (piezoelectric, silicon, etc.), shapes and types (machined elements, chip-based, etc.), and / or various manufacturing methods.

[0082] The transducers are designed and optimized for clinical applications (e.g., abdominal tumors, peripheral vascular diseases, fat ablation, etc.) and desired outcomes (e.g., acoustic cavitation / tissue destruction without thermal damage to intervening tissues), offering a wide range of operation from relatively shallow and superficial targets (e.g., thyroid or breast nodules) to deeper, more difficult-to-reach targets such as tumors in the liver or central brain. They can be configured to enable acoustic cavitation / tissue destruction under a variety of parameters and sets, including but not limited to frequency, pulse repetition rate, pulses, pulse count, pulse length, pulse period, delay, repetition, synchronization delay, synchronization period, synchronization pulse, synchronization pulse delay, various loop sets, and others, and their permutations, which are activated by the aforementioned system components (such as function generators and amplifiers). The transducers can also be designed to activate drug payloads deposited in tissues by various methods, such as injection, placement, or delivery via micelles or nanostructures.

[0083] Integrated imaging The disclosed system incorporates various imaging techniques, enabling users to visualize, monitor, collect / use feedback on the patient's anatomical structure, relevant areas of interest, treatment / procedure sites, and surrounding or intervening tissues to evaluate, plan, and execute procedures, and adjust treatment parameters as needed. Imaging techniques include ultrasound, X-ray, CT, MRI, PET, fluoroscopy, optical imaging, contrast-enhanced imaging, and / or various combinations thereof. Furthermore, it is disclosed that various image processing and characterization techniques can be used to enhance visualization and support user decision-making. These can be manually selected or indicated by the user, or automatically selected or indicated by the system. The system can be configured to enable parallel display, switching display, overlay display, 3D reconstruction, segmentation, registration, multimodal image fusion, image flow, and / or any methodology that allows users to identify, define, and inform about various aspects of how images are used during a procedure, which are displayed in the system's various user interfaces and displays. Examples include locating, indicating, and characterizing areas of interest, organ systems, and potential treatment sites within, on, and / or surrounding organs and tissues; identifying important structures such as tubes, blood vessels, nerves, ureters, fissures, capsules, tumors, tissue damage / disorders / diseases, other organs, connective tissue, and / or their interrelationships (e.g., lymphatic vessels or vascular systems draining lymph from a tumor, or the proximity of a tumor to an organ capsule or other underlying organs), but these examples are countless.

[0084] The system is configured to include onboard integrated imaging hardware, software, sensors, probes, and wetware, and may also be configured to communicate and interface with external imaging and image processing systems. The aforementioned components may be incorporated into the system's therapeutic subsystem components, including probes, imaging arrays, etc., and may also be incorporated electrically, mechanically, or electromechanically into therapeutic transducers. This allows for geometric alignment of imaging and treatment, potentially enabling the treatment to be positioned directly within the field of view and, in some cases, in a straight line with imaging. In some embodiments, this integration may include a fixed orientation of the imaging function (e.g., imaging probe) in relation to the therapeutic transducer. In other embodiments, the imaging solution can be moved or adjusted in position, including by changing angle, extension (e.g., distance from the therapeutic transducer or patient), rotation (e.g., imaging plane in the case of an ultrasound probe), and / or other parameters, and may also be dynamically moved / adjusted during active imaging. The imaging component or probe may be encoded to specify its orientation and position relative to other elements of the system, such as therapeutic transducers or robotic positioning components.

[0085] In one embodiment, the system includes onboard ultrasound and is further configured to allow the user to visualize, monitor, and receive feedback on the treatment site via a system display and software that enables ultrasound imaging and characterization (and in various forms), ultrasound-guided planning, and ultrasound-guided treatment, all in real time. The system can be configured to allow the user to take images of the patient in a manual, semi-automatic, or fully automated manner (e.g., using an imaging device with manual or robotic functions).

[0086] In some embodiments, imaging feedback and monitoring may include monitoring of changes in: backscattering from bubble clouds; speckle reduction in backscattering; backscatter speckle statistics; mechanical properties of tissue (i.e., elastography); tissue perfusion (i.e., ultrasonic contrast); shear wave propagation; acoustic emission; electrical impedance tomography; and / or various combinations thereof (including those displayed or integrated with other imaging formats such as CT and MRI).

[0087] In some embodiments, imaging including feedback and monitoring from backscatter from bubble clouds can be used as a method to immediately determine whether a tissue disruption process has started, is being adequately maintained, or has ceased. For example, this method allows for continuous real-time monitoring of drug delivery or tissue erosion. The feedback function can also be used to initiate the tissue disruption process at a higher intensity and then maintain it at a much lower intensity. For example, backscatter feedback can be monitored by any transducer or ultrasound imager. By measuring the feedback from a therapeutic transducer, an auxiliary transducer can be configured to transmit exploration pulses or passively detect cavitation. Furthermore, the nature of the received feedback can be used to adjust acoustic parameters (and associated system parameters) to optimize drug delivery or tissue erosion processes.

[0088] In some embodiments, imaging including feedback and monitoring from backscatter, and speckle reduction may be configured in the system.

[0089] In systems involving backscattering feedback and monitoring, if the background tissue is mechanically and gradually fragmented—in other words, homogenized, destroyed, or eroded—this process results in changes in the size and distribution of acoustic scattering. At some point in the process, the size and density of the scattering particles are reduced to a level where ultrasound scattering is minimal or significantly reduced. This significantly reduces speckle. Speckle is a coherent interference pattern of light and dark spots that appears in images when a coherent light source (in this case, ultrasound) is used. As treatment time elapses, the reduction in speckle noise causes dark areas to appear within the treatment area. The amount of reduction in speckle noise is related to the degree of tissue fragmentation and can therefore be correlated with the size of the remaining tissue fragments. When this size is reduced to a subcellular level, it is assumed that no viable cells exist. Therefore, treatment can be continued until the desired level of speckle reduction is reached. Speckle can be easily observed and evaluated with standard ultrasound imaging equipment. Changes in backscattering can also be evaluated using specialized transducers and systems, including those disclosed herein.

[0090] Furthermore, in systems that include speckle-based feedback and monitoring, the image persists from frame to frame and remains largely unchanged, provided that the scattering distribution in the background does not change and there is no movement of the object being imaged. However, the size of the scattering particles may change sufficiently to be detectable by means of signal processing, long before they become small enough to cause speckle reduction. This set of techniques functions as a device for detecting changes in speckle statistics. For example, the size and location of one or more specks in an image begin to lose correlation before visible speckle reduction occurs. A decrease in speckle correlation after appropriate motion correction can be a highly sensitive indicator of mechanical tissue damage and, consequently, an indicator of therapeutic effectiveness. This feedback and monitoring technique makes it possible to observe changes caused by acoustic cavitation / tissue destruction processes early, and to identify tissue changes before substantial or complete tissue impact (e.g., erosion) occurs. In one embodiment, this method can be used to monitor acoustic cavitation / tissue destruction processes to enhance drug delivery when the treatment site / tissue is temporarily destroyed and tissue damage / erosion is undesirable. In other embodiments, this may include speckle decoherence due to the movement of scatterers within the treatment volume as fluidization progresses, for example, when partial or complete tissue erosion is desired.

[0091] In a system that includes elastography-based feedback and monitoring, and as background, when the treatment site / tissue is further subdivided by acoustic cavitation / tissue destruction effects (homogenization, destruction, or erosion), its mechanical properties change from a soft, interconnected solid to a viscous fluid or paste with little long-range interaction. These changes in mechanical properties can be measured by various imaging methods, such as MRI and ultrasound imaging systems. For example, it is possible to generate force (i.e., radiant force) in a localized volume of tissue using ultrasound pulses. During tissue destruction treatment, the tissue's response (displacement, strain, velocity) can change significantly, and the state of tissue destruction can be determined by imaging and other quantitative means.

[0092] The system may also include feedback and monitoring based on changes in shear wave propagation. As background, tissue fragmentation makes tissue more fluid and less solid, and fluid systems generally do not propagate shear waves. Thus, the degree of tissue fluidization provides an opportunity for feedback and monitoring of the tissue destruction process. For example, shear wave propagation can be observed using ultrasound or MRI imaging systems. The disappearance of such waves in the treated area is used as an indicator of the degree of tissue destruction or damage. In some system embodiments, interacting shear waves can be generated and measured using the system and its supporting subsystems. For example, two adjacent ultrasound foci may disturb the tissue by pushing it in a specific direction. If the adjacent foci are in a fluid, the shear waves do not propagate and do not interact with each other. If the tissue is not fluidized, the interaction is detected by external means. For example, it can be detected by the difference frequency, which is only detected when two shear waves interact nonlinearly, and its disappearance correlates with tissue damage. Therefore, the system can be configured to enhance feedback and monitoring of acoustic cavitation / tissue destruction treatment using this method.

[0093] In systems involving acoustic emission feedback and monitoring, the background is that as tissue volume is subdivided, its effect on acoustic cavitation / tissue destruction (e.g., bubble clouds in this case) changes. For example, bubbles may grow larger, and their lifespan and disintegration characteristics may differ between intact and fluidized tissue. After tissue subdivision, bubbles may move and interact, generating larger bubbles or cooperatively interacting with each other, all of which can lead to changes in acoustic emission. These sound waves are audible during treatment and change as treatment progresses. By analyzing these changes and examining their correlation with treatment effectiveness, it becomes possible to monitor the progress of treatment, and this can be configured as a function of the system.

[0094] In a system that includes feedback and monitoring using electrical impedance tomography, an impedance map of the treatment site can be created as background information, based on the spatial electrical characteristics of the entire treatment site. An image of the conductivity or dielectric constant of the patient's treatment site can be estimated by performing electrical measurements of the skin surface. Conductive electrodes are attached to the patient's skin, and a weak alternating current is passed through some or all of the electrodes. One or more known currents are injected into the skin surface, and the voltage is measured at multiple points using the electrodes. This process can be repeated for various configurations of applied current. The resolution of the resulting image can be adjusted by changing the number of electrodes used. From the impedance map, the electrical characteristics of the treatment site within the skin surface can be measured, and this information, comprised of the system and support subsystems, can be used to monitor changes and locations of acoustic cavitation / tissue destruction (especially bubble clouds, etc.) and tissue destruction processes.

[0095] The user can further select, annotate, mark, highlight, and / or contour various regions of interest or treatment sites, and defined treatment targets (on the image), which can be used to instruct the system on where to image, test, and treat, via the system software, user interface, and display. Depending on the configuration, the user may perform the examination using a manual ultrasound probe (e.g., a diagnostic handheld probe). In other configurations, the system may perform the examination using a robot or electromechanical positioning system, either according to the system's instructions or in an automated manner. Conversely, the system can also combine manual and automated use.

[0096] The system may further include the ability to perform image registration, which includes the registration of images and image datasets to enable the system's navigation and localization to the patient, including treatment sites (e.g., tumors, important structures, anatomical structures of bone, anatomical structures, identifying features, etc.). In one embodiment, the system uses integrated ultrasound to image and identify a region of interest, such as the liver, and allows for the selection and marking of tumors (or alternative markers) within the liver, which are displayed via / on the system software. The system also registers image data in a coordinate system defined by the system, thereby enabling the system's therapeutic subsystem and robotic subsystem to perform synchronized acoustic cavitation / tissue ablation therapy on the marked tumors. The system may include the ability to register various image sets, including those disclosed herein, with each other, and the ability to provide navigation and localization (e.g., aligning a therapeutic transducer to a CT or MRI / ultrasound fusion image, with the therapeutic transducer and robotic subsystem tracking the image).

[0097] This system can be capable of operating in a variety of interventions, endoscopic and surgical environments, either alone or in conjunction with other systems (surgical / laparoscopic towers, vision systems, endoscopic systems and towers, ultrasound-enabled endoscopic ultrasound (flexible and rigid), percutaneous / endoscopic / laparoscopic and minimally invasive navigation systems (optical, electromagnetic, shape-sensing, ultrasound-enabled, etc.)), and can also operate in conjunction with various optical imaging capabilities (fiber optic and / or digital, etc.). The disclosed system can be configured to operate in conjunction with these systems, and in some embodiments it operates in coordination with these systems, while in other embodiments all or part of the system is integrated into the above systems / platforms (e.g., endoscopic systems or laparoscopic surgical robots with acoustic cavitation / tissue destruction capabilities). In many of these environments, therapeutic transducers may be used, for example, during or before / after the use of optically guided endoscopes / bronchoscopes, or, as another example, when a laparoscopic robot (e.g., the Intuitive Da Vinci* Xi system) is observing / manipulating tissue / treatment sites. Furthermore, these embodiments and examples include cases where the other systems / platforms are used to supply fluid (locally) to enable the creation of artificial acoustic windows that do not normally exist (e.g., when fluidizing a segment or lobe of the lung in preparation for acoustic cavitation / tissue destruction by non-invasive transthoracic treatment (e.g., placing transducers externally on or around the patient's body)). The systems disclosed herein may also include all or part of subsystem hardware packaged within the other system carts / consoles / systems described herein (e.g., acoustic cavitation / tissue destruction systems and / or subsystems integrated and operated from the navigation system or laparoscopic system).

[0098] The system can also be configured to display real-time visualization of bubble clouds spatially and temporally using the various parameters mentioned above and other parameters, including pre- and post-treatment tissue effects due to the interaction between tissue and bubble clouds. The system can dynamically image, visualize, and display bubble clouds and their changes (e.g., decrease or increase in echo intensity), including intensity, shape, size, location, morphology, and persistence. These features allow users to continuously track and follow treatment in real time through an integrated single procedure and interface / system, and to confirm the safety and effectiveness of the treatment on the spot (other interventional or surgical treatments may require multiple procedures to achieve the same results, or treatment effects may not be confirmed in real time (e.g., radiotherapy), or may not be possible (e.g., real-time visualization of local tissue during thermal ablation), and / or other procedures may require more invasive approaches (e.g., incision or puncture) and repeated imaging with a scanner between procedural steps (e.g., CT or MRI scans)). The systems, subsystems, components, modalities, functions, and workflows / usages disclosed above can be implemented without limitation through enabling hardware, software, user interfaces, and usage environments, and future improvements, enhancements, and inventions in this art, as well as the resulting data and means of using such data for analytics, artificial intelligence, or digital health applications and systems, are deemed to be included within the scope of this disclosure.

[0099] Robotics The system comprises various robotic subsystems and components, including but not limited to one or more robotic arms and controllers, which can work in conjunction with other subsystems or components of the system to irradiate and monitor acoustic cavitation / tissue damage. As mentioned above, the robotic arms and control systems can be integrated into one or more cart configurations.

[0100] For example, one system embodiment includes a cart with an integrated robotic arm and control system, treatment, integrated image processing, and software, where the robotic arm and other enumerated subsystems are controlled by the user via the form of a single bedside cart.

[0101] In other embodiments, the robot subsystem may consist of one or more independent carts, which are driven in a master / slave configuration from another master or cart, with the robot-equipped cart positioned beside the bed / patient and the master located at a distance from the cart.

[0102] The disclosed robotic arm comprises multiple joints, segments, and degrees of freedom and may include various integrated sensor types and encoders implemented for a variety of applications and safety features. Sensing technologies and data may include, for example, vision, potentiometers, position / location, kinematics, force, torque, velocity, acceleration, dynamic load, and / or others. In some cases, sensors may be used to give commands to the robot (e.g., to manually move the robot to a preferred installation location or return it to its home position). Further details regarding the robotic arm are described in U.S. Patent Publication 2013 / 0255426 by Kassow et al., which is disclosed in full by reference herein.

[0103] The robotic arm receives control signals and commands from a robotic control system housed within a cart. This system can be configured to provide a variety of functions, including positioning, tracking, pattern recognition, triggering, and event / action control.

[0104] The positions may be configured to include fixed positions, pallet positions, time-controlled positions, distance-controlled positions, variable time-controlled positions, and variable distance-controlled positions.

[0105] The tracking may be configured to include time-controlled tracking and / or distance-controlled tracking.

[0106] The movement pattern may be configured to include not only a sequence of positions along a defined path in space, but also intermediate positions or waypoints.

[0107] The trigger may be configured to include distance measuring means, time, and / or visual / image-based, force, torque, localization, energy / power feedback, and / or various other sensor means, including but not limited to those disclosed herein.

[0108] Events / actions can be configured to include a variety of examples, such as proximity-based actions (approaching / moving away from a target object), activation or deactivation of various end-effectors (e.g., therapeutic transducers), starting / stopping / pausing event sequences, triggering or switching event / action triggers, starting and changing / switching behavior patterns, and / or time-based and temporal actions across defined tasks and time spaces.

[0109] In one embodiment, the system comprises a three-degree-of-freedom robot positioning system, where the user can fine-tune the therapeutic transducer via the X, Y, Z coordinate system (via the system's software and associated user interface), and the rough positioning of the transducer (e.g., placement of the transducer on the patient's body) is done manually. In some embodiments, the robot may have six degrees of freedom, including X, Y, Z, and pitch, roll, and yaw. In other embodiments, the robot subsystem may have further degrees of freedom, such as positioning the robot arm support base along a linear axis running parallel to the general direction of the patient surface, or adjusting the height of the support base vertically, thereby changing the position of the robot arm relative to the patient, patient surface, cart, coupling subsystem, additional robots / robot arms, and / or additional surgical systems (including, but not limited to, surgical towers, imaging systems, endoscopic / laparoscopic systems, and / or others).

[0110] One or more robotic arms may have various functions to assist in manually or semi-manually manipulating and changing the position of the arm, and these functions may interface with the therapeutic transducer at or between the most distal joints of the robotic arm. In some embodiments, this function is configured to include a handle that allows manipulation and manual control by one or more hands. The handle is configured to include user input and electronic control functions of the robotic arm, to instruct various drive functions or modes, and to actuate the robot to assist in rough positioning or fine adjustment of the arm (e.g., activating or deactivating a free drive mode). The workflow for initial positioning of the robotic arm and therapeutic head can be configured to allow the user to choose between two workflows: first placing the therapeutic transducer / head in the coupling solution and directly connecting the therapeutic transducer to the arm, or, as an alternative workflow, first setting up the coupling solution and then connecting the robotic arm to the therapeutic transducer / coupling solution as a later / final setup step.

[0111] In some embodiments, the robotic arm comprises a robotic arm on a laparoscope, single-port, endoscopic, hybrid, or combination thereof, and / or other robot, where the robot in the system is a slave to a master controlling the arm, and may further comprise several other arms equipped to simultaneously perform other tasks (such as visualization, image processing, grasping, cutting, ligation, sealing, closure, stapling, ablation, suturing, marking, etc.), including the operation of one or more laparoscopic arms (and instruments) and various tissue destruction system components. For example, a laparoscopic robot may be used to prepare the surgical site, which may include manipulating the position of organs to ensure more ideal acoustic access, or in some cases further stabilizing organs to minimize respiratory movement. In parallel with this, a second robotic arm may be used to irradiate non-invasive acoustic cavitation through the body cavity, as observed by real-time images from a therapeutic transducer (e.g., ultrasound) and simultaneous visualization by a laparoscopic camera. Other relevant aspects include similar approaches combining endoscopic and non-invasive approaches, as well as approaches combining endoscopic, laparoscopic, and non-invasive approaches.

[0112] software This system may include a variety of software applications, functions, and components that enable users to operate, control, and use the system to perform numerous clinical applications. The software can communicate with and work in conjunction with one or more subsystems, including but not limited to therapeutic, integrated imaging, robotics, and other components, assistive devices, and accessories.

[0113] Overall, without specifying a particular order of importance, the software can provide: system initialization and setup, system maintenance, data communication and import / export / save, user modification / operation / configuration / control / command of various settings and parameters, safety and risk mitigation related to use, procedure planning, support for various configurations of transducers, robotic arms and drive systems, function generators and amplifier circuits / slaves, ultrasound sequences for testing and treatment, transducer steering and positioning (electromechanical and electron beam steering, etc.), treatment patterns, imaging and imaging probe support, manual and electromechanical / robot movement, imaging support for measurement / characterization of various dimensions within or around the procedure and treatment site (e.g., depth from one anatomical site to another), pre-treatment evaluation, protocols for: Measurement / characterization of situ treatment site characteristics and condition (e.g., acoustic cavitation / tissue destruction threshold and heterogeneity), targeting and target alignment, calibration, marking / annotation, localization / navigation, registration, guidance, workflow, provision and guidance of procedure steps, autonomous execution of treatment plans and protocols, autonomous execution under direct monitoring and viewing with real-time imaging displayed through the software, display with various views and viewports, communication tools (video, audio, sharing, etc.), troubleshooting, provision of instructions, warnings, alerts, and / or permission to communicate via various network devices and protocols.Furthermore, the software's user interface and support displays are intended to consist of various buttons, commands, icons, graphics, text, etc., that enable users to interact with the system in a user-friendly and effective manner, presented in countless combinations, layouts, and designs, and are intended to be displayed in similar or different ways or with different sets of functions for systems consisting of multiple displays (such as touchscreen monitors and touchpads), and / or systems that network with one or more external displays or systems (such as another robot, navigation system, system tower, console, monitor, touch display, mobile device, tablet, etc.).

[0114] This software can support the various function generators (e.g., FPGAs), amplifiers, power supplies, and therapeutic transducers mentioned above as part of a typical system including one or more computer processors. The software can be configured to allow the user to select, determine, and monitor various parameters and settings related to acoustic cavitation / tissue destruction, and to stop / start / modify these parameters and settings after observing / receiving feedback on performance and status.

[0115] The software can be configured to allow the user to select from a list or menu of multiple transducers and to support automatic detection of the transducer (and verification of appropriate sequence and parameter settings based on the selected application) when connecting to the system. In other embodiments, the software can update target and amplifier settings (e.g., number of channels) based on the selected transducer. The software can also provide transducer recommendations based on pre-processing and planning inputs. Conversely, if there is an error in the selection or parameters of a therapeutic transducer, amplifier, and / or function generator, or if a failure or malfunction occurs, the software may display an error message or warning to the user, including a report of its details and location.

[0116] In addition to the above, the software is configured to allow users to select treatment sequences and protocols from a list or menu, and the selected sequences and protocols, and / or previously selected sequences and protocols, can be associated with and saved to specific clinical uses or patient profiles. Associated profiles may include relevant patient, procedure, clinical, and / or engineering data that can be used to provide, modify, and / or guide information about current or future treatments or procedures / interventions, either as decision support or as an active part of the procedure itself (e.g., building and inducing new therapies using sequential datasets).

[0117] As part of the planning process or during treatment, the software (and in conjunction with other components of the system) enables the evaluation and testing of acoustic cavitation / tissue destruction thresholds at various locations within a user-selected region of interest or a defined treatment area / volume, determining a minimum cavitation threshold across the region or the entire area / volume, and ensuring that treatment parameters are optimized to achieve, maintain, and dynamically control acoustic cavitation / tissue destruction. In one embodiment, the system allows the user to manually evaluate and test threshold parameters at various points. These points include defined boundaries, inside the boundaries, and central locations of the selected region of interest and treatment area / volume. At these points, the obtained threshold measurements are reported / displayed to the user and used to update treatment parameters before treatment. In another embodiment, the system may be configured to enable automated threshold measurement and updating, as implemented by the robot subsystem described above, in which case the user can either direct the robot or command the robot to perform measurements autonomously.

[0118] The software can also be configured to work in conjunction with a computer processor and one or more function generators, amplifiers, and therapeutic transducers to enable various combinations for delivering and positioning optimized acoustic cavitation / tissue destruction within and across a selected region / volume. This includes, but is not limited to, systems consisting of fixed / natural focus placements using purely electromechanical positioning configurations, electron beam steering (with or without electromechanical positioning), electron beam steering to a new selected fixed focus with further electromechanical positioning, axial (Z-axis) electron beam steering with lateral (X and Y) electromechanical positioning, high-speed axial electron beam steering with lateral electromechanical positioning, high-speed beam steering in 3D space, and various combinations including dynamically changing one or more acoustic cavitation / tissue destruction parameters based on the aforementioned capabilities that update therapeutic parameters based on threshold measurements (e.g., dynamically adjusting amplitude across the entire therapeutic region / volume).

[0119] Other components, auxiliary parts, and accessories The system may include, but is not limited to, computers, computer processors, power supplies including high-voltage power supplies, controllers, cables, connectors, network devices, security, communications, software applications for integration into information systems including hospital information systems, mobile phone communication devices and modems, wired or wireless handheld controllers, goggles or glasses for advanced visualization, augmented reality or virtual reality applications, cameras, sensors, tablets, smart devices, telephones, Internet of Things enabling functions, special-purpose "apps" or user training materials and applications (software or paper-based), virtual proctors or trainers, and / or other enabling functions, devices, systems or applications, and / or the methods of use described above, a variety of other components, auxiliary devices and accessories.

[0120] System variations and methods / applications In addition to performing a wide range of procedures, this system can also provide additional benefits such as advanced planning, image processing, and guidance to assist the user. In one embodiment, the system allows the user to create a treatment plan tailored to the patient, target, and application, and the system can be configured to optimize treatment parameters based on feedback to the system during planning, and the plan may further include the ability to perform various test protocols to collect specific inputs to the system and the plan.

[0121] Feedback may include various energy, power, location, position, organization, and other parameters.

[0122] The system and the feedback described above can be further configured and used to autonomously (robotically) execute optimized treatment plans and protocols, visualized in real-time images during the procedure, allowing the user to directly observe the local therapeutic tissue effects as the treatment progresses and to start / stop / modify the treatment at their discretion. Examination and treatment protocols may be updated during the procedure at the user's direction or, in some embodiments, based on logic built into the system.

[0123] Many of these advantages have the potential to further improve other forms of acoustic therapy, such as high-intensity focused ultrasound (HIFU) thermal ablation and high-intensity therapeutic ultrasound (HITU) including boiling tissue disruption (thermal cavitation), and are recognized as part of this disclosure. This disclosure also explores the application of histotripsy as a means of activating the activity of a previously delivered active drug payload by protection with micelles, nanostructures, or similar protective structures, or by molecular arrangements that enable activation only when irradiated with acoustic energy.

[0124] In another embodiment, the therapeutic subsystem comprises one or more amplifiers, transducers, and power supplies and is configured to enable multiple acoustic cavitation and tissue destruction driving functions, providing specific advantages based on application, method, and / or patient-specific use. These advantages include, but are not limited to, the ability to better optimize and control therapeutic parameters. This makes it possible to deliver more energy with a more desirable thermal profile, increase the treatment rate, reduce the procedure time, or enable electron beam steering or other functions.

[0125] This disclosure also includes novel systems and concepts relating to systems and subsystems including novel and "general-purpose" amplifiers that enable multiple drive modes (e.g., single-cycle and multi-cycle pulses). In some embodiments, this may include various novel features to further protect the system and user with respect to electrical safety and other hazards (e.g., damage to transducer and / or amplifier circuits).

[0126] On another level, the system and therapeutic subsystems include numerous therapeutic transducers, which are configured for specific applications and uses, capable of accommodating a wide range of operating parameters (target size, depth, location, etc.) and having a wide range of operating specifications (detailed below). The transducers can be further adapted and interfaced with robot-enabled systems and coupling subsystems, allowing the transducers to be positioned within or parallel to acoustic coupling devices, enabling simultaneous imaging and tissue destruction therapy through an acceptable acoustic window in many embodiments. The therapeutic transducers may include an integrated imaging probe or localization sensor that displays and determines the transducer's position within the treatment site and provides a direct view (or representation) of the treatment site, and the appearance and intensity of acoustic cavitation / tissue destruction tissue effects and bubble clouds may or may not change throughout the treatment and depending on their location within the treatment site (e.g., tumor, surrounding healthy tissue, vital structures, adipose tissue, etc.).

[0127] The systems, methods, and uses of the systems disclosed herein may be beneficial in overcoming important unmet needs in various fields of surgery, including soft tissue ablation, oncology, immuno-oncology, advanced image-guided procedures, open surgery, laparoscopic surgery, single-incision surgery, natural orifice surgery, endoscopic surgery, non-invasive surgery, and various combinations thereof; various intervention spaces for catheter-based procedures in vascular, cardiovascular, pulmonary and / or neurocranial-related areas; cosmetic / aesthetics, metabolism (e.g., type 2 diabetes), plastic and reconstructive surgery, ophthalmology and ophthalmology, orthopedics, gynecological and male health; and other systems, devices and methods for treating disease, injury, undesirable or healthy tissue, organ or cell.

[0128] Furthermore, systems and methods are provided to improve intra-tissue treatment patterns, which can shorten treatment time, improve effectiveness, and reduce the amount of energy delivered to the patient and the amount of pre-focus tissue heated.

[0129] Usage environment The disclosed systems, methods of use, and use of the systems can be implemented in a multitude of environments and settings, including, but not limited to, treatment rooms, operating rooms, hybrid rooms, inpatient and outpatient environments, outpatient environments, imaging centers, radiology departments, radiotherapy departments, oncology departments, surgical departments, and / or any medical center, with or without various support systems such as anesthesia, as well as physicians' offices, mobile medical centers or systems, automobiles and related vehicles (e.g., vans), aerospace and sea transport vehicles such as airplanes and ships, and / or any structure capable of providing temporary treatment support (e.g., tents). In some cases, the systems and / or subsystems disclosed herein may be provided as functions integrated into other environments, for example, when a tissue ablation therapy subsystem is directly integrated into an MRI scanner or patient surface / bed (in which case at least the treatment generator and transducer are integrated therein), or when the tissue ablation configuration further includes a robotic positioning system, which is also integrated into the scanner or bed central design.

[0130] Coupling The system may include various coupling subsystem embodiments enabled and configured to allow acoustic coupling to the patient to enable effective acoustic access for ultrasound visualization and acoustic cavitation / tissue disruption (e.g., providing and supporting an acoustic window and medium between the transducer and the patient). These may include devices in various shapes, including open and closed device solutions, and several configurations that can be configured to dynamically control the acoustic medium (temperature, dissolved gas content, particle filtration level, sterility, volume, composition, etc.). Such dynamic control components may be directly integrated into the system (in the cart) or may be located in a separate external device or cart, communicating with the system intermittently / intermittently or continuously.

[0131] A coupling subsystem typically comprises at least a coupling medium (e.g., degassed water or aqueous solution), a reservoir / container for containing the coupling medium, and a support structure (including interfaces with other surfaces or devices). In most embodiments, the coupling medium is water, which may be prepared before or during processing (e.g., by cooling, degassing, or filtering). A variety of adjustment parameters can be employed depending on the system configuration and its application.

[0132] Reservoirs or media containers can be formed in various sizes and shapes to conform to the patient and allow therapeutic transducers to act within the acoustic medium, and to meet the defined required working space (such as the minimum volume of medium necessary to allow therapeutic transducers to be positioned and / or moved at one or more therapeutic positions or patterns and at various distances or depths from the patient). The reservoir or media container may also mechanically support the load and load distribution using mechanical and / or electromechanical support structures. Typical examples include support frames. Containers vary in shape, size, curvature, and dimensions, and are composed of various material configurations (single material, multiple materials, composite materials, etc.), the configuration of which can vary throughout. In some embodiments, insertable and removable components such as films, drapes, membranes, and bellows are included, and these components are incorporated internally to conform to the patient and help contain the medium within the container. Furthermore, it may also include various sensors (e.g., volume / fill level), drains (e.g., inlet / outlet), lighting (e.g., LEDs), markings (e.g., filling line, installation direction, etc.), and text (e.g., labels).

[0133] In some embodiments, the reservoir or medium container includes a sealable frame, and by arranging a membrane and / or film inside it, provides a suitable means for contacting the reservoir (later including a treatment head / treatment transducer) as an interface with the patient, and further provides a barrier to the medium (e.g., water) between the patient and the treatment transducer. In other embodiments, the membrane and / or film has an opening, and its patient contact edge provides a fluid / mechanical seal to the patient, but in contrast, allows the medium to communicate directly with the patient (e.g., a direct interface between degassed water and the patient). The superstructure of the storage tank or medium container in these two examples can be open or sealed at the proximal portion of the structure (e.g., the top) (e.g., to prevent spillage or to provide additional functionality).

[0134] The membranes of this disclosure may consist of various elastomers, viscoelastic polymers, thermoplastic resins, thermoplastic elastomers, thermosetting polymers, silicones, urethanes, rigid / flexible copolymers, block copolymers, random block copolymers, and the like. The materials can be hydrophilic, hydrophobic, surface modified, coated, extracted, etc., and may also contain various additives to improve performance, appearance, and stability. In some embodiments, the thermoplastic elastomer may be styrene-ethylene-butylene-styrene (SEBS) or other elastomers with similar strength and flexibility. The shape of the membrane may be flat or pre-formed before use. In other embodiments, the membrane is inelastic (i.e., convex) and can be pressed against the patient's skin to acoustically bond the transducer to the tissue. Furthermore, systems and methods for controlling the level of contaminants (e.g., particulate matter) on the membrane to maintain an appropriate ultrasonic coupling level are also disclosed. Too much particulate matter or contaminants can scatter ultrasound. To prevent this, a peelable film or coating on the surface of the membrane is an effective method to prevent contamination.

[0135] The material can be formed into useful membranes by molding, casting, spraying, ultrasonic spraying, extrusion, and / or other processing methods that produce useful embodiments. These may be disposable or reusable. They may be supplied in a non-sterile, aseptically cleaned, or sterilized state, and sterilization may include any known method, such as ethylene oxide, gamma rays, electron beams, autoclaves, steam, peroxides, plasma, and chemicals. The membrane may be further constructed with a molded or overmolded frame on the outside, which provides mechanical stability to the membrane during handling, including assembly, setup, and disassembly of coupling subsystems. Various parameters of the membrane can be optimized to suit this use. These include thickness, thickness profile, density, and composition (polymer molecular weight to copolymer ratio, additives, plasticizers, etc.), and in particular, optimization to maximize acoustic transmission properties, minimize impact on the cavitation onset threshold, and minimize ultrasonic image artifacts, including membrane reflections.

[0136] Open-type storage tanks or media containers offer various filling methods, including the use of pre-prepared media or water, and may be supplied with water of specific specifications (temperature, gas saturation, etc.). They may also include additional features essential for filling and discharging (ports, valves, hoses, tubes, fittings, bags, pumps, etc.). These features can be integrated into or integrated with other devices, such as fluid control systems. Fluid control systems may be culture medium preparation systems located in hospital or nursing home rooms, or conversely, mobile cart-based systems that can prepare and transport culture media from carts to culture medium containers.

[0137] The sealed reservoir or medium container may have various sealing functions, in some embodiments sealing to the proximal / upper portion or structure of the reservoir / container, and in other embodiments sealing to a function on the transducer or transducer housing. Furthermore, in some embodiments, the fluid volume in these designs may be dynamically controlled to minimize the possibility of bubbles or turbulence in the fluid and to change the focal distance to the target region without moving the transducer. Therefore, an integrated function enabling fluid communication and fluid control (a function to supply / remove fluid on demand) may be provided, which includes the ability to monitor and control various fluid parameters as described above. To achieve this function, the entire system, and the coupling subsystem as a part thereof, may have a fluid conditioning system, which may include various electromechanical devices, systems, power supplies, sensing, computing, pumps, filtering, control systems, etc. The reservoir may also be configured to receive signals that cause deformation or shape changes in a specific controlled manner so that the target point can be adjusted without moving the transducer.

[0138] The coupling support system may include various mechanical support devices for connecting a reservoir / container and medium to a patient and workspace (bed, floor, etc.). In some embodiments, the support system comprises a mechanical arm having three or more degrees of freedom. This arm may have a proximal interface with one or more positions (and features) of the bed (including, but not limited to, frames, rails, custom rails or inserts), and may further have an interface with one or more distal positions of the reservoir or container. The arm may also be a function implemented on one or more carts, which can be configured in various and unlimited combinations, and in some cases, the carts are solely responsible for supporting and providing the disclosed support structure.

[0139] In some embodiments, the support structure and arm may be a robotic arm implemented as a standalone cart, or a robotic arm integrated into a cart further including two or more system subsystems, and the robotic arm may be the arm of another robot of an interventional, surgical, or other type, and may further include various user input functions for actinguating / controlling the robotic arm (e.g., positioning into a coupling medium) and / or coupling solution functions (e.g., filling, discharging, etc.). In some examples, a position encoder of the support structure robotic arm can be used to coordinate the operation of a second arm (e.g., including a therapeutic transducer / therapeutic head) to position the therapeutic transducer in a desired / known position and orientation within the coupled support structure.

[0140] Overall, there are numerous unmet needs in today's interventional and surgical medical procedures, including those using minimally invasive devices and approaches to treat disease and injury, and these unmet needs could be addressed by entirely new medical procedures. The capabilities of today's medical systems are often limited by access constraints, where less invasive or non-invasive approaches are desirable, where current tools cannot achieve the desired / necessary tissue effects (e.g., surgery around / inside critical structures without causing significant damage), or where the physical configuration of the system makes certain procedures undesirable or impossible. Furthermore, combining multiple approaches and enhancing the therapeutic effects on tissue can enable entirely new procedures and approaches that are currently impossible.

[0141] Furthermore, there is a specific need to enable the implementation of tissue ablation therapy, including robotic tissue ablation therapy. In this robotic tissue ablation therapy, one or more tissue ablation transducers are configured to acoustically bind to the patient using a completely sealed approach (e.g., the acoustic medium does not communicate with the patient's skin), allowing the one or more tissue ablation transducers to move within the binding solution without interfering with the movement of the robotic arm or interfering with or disrupting the binding interface which could affect the intended treatment or target site.

[0142] This specification discloses (but is not limited to) tissue-disruption acoustic systems and patient-binding systems and methods that enable tissue-disruption therapy / treatment in any environment, including intervention rooms, operating rooms, hybrid suites, diagnostic imaging centers, medical centers, office environments, mobile treatment centers, and / or other environments. The following disclosures further detail novel systems used for creating, controlling, maintaining, modifying / enhancing, monitoring, and setting up / removing acoustic and patient-binding systems in a variety of approaches, methods, environments, architectures, and workflows. Generally, the disclosed novel systems enable the connection of a binding medium (in some examples, degassed water) between a tissue-disruption therapy transducer and a patient. The acoustic medium provides sufficient acoustic coupling to the patient, enabling the user to deliver tissue-disruption pulses through a desired treatment site (and volume). Delivery may require the physical movement of the tissue-disruption therapy transducer within a defined workspace containing the binding medium, and the binding system is configured to allow the treatment transducer (and positioning system, e.g., robot) to move freely without being hindered by a binding support system (e.g., a frame or manifold holding the binding medium).

[0143] Coupling systems and subsystems / components The disclosed tissue-disruption acoustic and patient coupling system may, but may not, include one or more of the following subsystems and components illustrated in Figure 2: 1) a membrane / barrier film for sealing and tightly adhering to the coupling between the patient and the tissue-disruption system; 2) a frame and assembly for holding the membrane and providing sufficient working space and headspace for the range of motion (x, y, z, pitch, roll, yaw) required for the histotripsy therapy transducer; 3) a sufficient amount of ultrasonic medium to interface the acoustic coupling with the tissue-disruption therapy transducer and robotic arm; 4) one or more mechanical support arms enabling the placement, positioning, and load-bearing of the frame, assembly, and medium; and 5) a fluid control system for preparing, supplying, and removing the ultrasonic medium from the frame and assembly.

[0144] In some embodiments, the coupling system may be completely sealed, while in other embodiments and configurations, it may be partially open to allow immediate physical and / or visual access.

[0145] Acoustic and patient-connected systems and subsystems may also have a variety of functions and characteristics, as well as associated workflows, and may be configured in various ways to enable tissue-disrupting procedures, as detailed below.

[0146] Figure 2 shows one embodiment of the tissue abrasion therapy and imaging system 200, including a coupling assembly 201. As described above, the tissue abrasion therapy and imaging system may include a therapeutic transducer 202, an imaging system, a robotic positioning arm 208, and a fluid cart 210. The robotic positioning arm can be mounted on a therapeutic cart such as a cart 209.

[0147] Therapeutic and / or imaging transducers can be housed within a coupling assembly 201, which may further comprise a coupling membrane 214 and a membrane restraint 216 configured to prevent the membrane from moving excessively away from the transducer. The coupling membrane can be filled with an acoustic coupling medium such as a fluid or gel. The membrane restraint is, for example, a semi-rigid or rigid material compared to the membrane and can be configured to limit the expansion / movement of the membrane. In some embodiments, the membrane restraint is not used, and over-expansion is prevented by the elastic and tensile strength of the membrane. The coupling membrane may be a SEBS membrane impregnated with mineral oil to prevent direct contact of bodily fluids with the patient's skin. In the illustrated embodiment, the coupling assembly 201 is supported by a mechanical support arm 218, which can support loads in the xy plane, but can be adjusted manually or automatically in the z-axis direction. The mechanical support arm can be mounted on the floor, a patient table, or a fluid cart 210. The mechanical support is designed and configured to hold the bonding membrane 214 in close contact with the patient's skin, while allowing the treatment / image transducer to move relative to the patient and relative to the bonding membrane 214 with the robot positioning arm 208.

[0148] The fluid cart 210 can include additional features such as a fluid tank 220, a cooling and degassing system, and a programmable control system. The fluid cart is configured to accommodate external loading of the coupling membrane with automatic control of the fluid sequence. Further details of the fluid cart are provided below.

[0149] Membrane / barrier film and related structures The membranes and barrier films are composed of a variety of biocompatible materials that allow for bonding that conforms to the patient's anatomical structure, with minimal or no trapped air bubbles that would interfere with ultrasound imaging and tissue ablation therapy, and can provide a sealed barrier layer between the ultrasound medium contained within the working space provided by the frame and assembly and the patient's anatomical structure.

[0150] Membrane and barrier film materials can include flexible and elastic biocompatible materials / polymers such as various thermoplastics and thermosetting materials, as well as permanent or bioabsorbable polymers. Furthermore, the UMC frame can also be constructed from the same materials. In some examples, the membrane may be made of pre-formed or flat, rigid or semi-rigid polymers.

[0151] ultrasonic medium As described above, the ultrasonic medium can include any applicable medium that can provide sufficient and useful acoustic coupling to enable tissue destruction therapy and adequate clinical imaging (e.g., ultrasound). The ultrasonic medium as part of the system may include, but is not limited to, a variety of aqueous solutions / mediums, including mixtures with other co-soluble fluids. These mediums may have preferred or more preferred acoustic properties, such as the ability to match the speed of sound. Examples include degassed water and / or mixtures / cosolutions of degassed water with various alcohols such as ethanol.

[0152] Mechanical support arm and arm structure To support acoustic and patient coupling systems, various mechanical support arms (and arm architectures) of different designs and configurations can be employed, including providing users with an efficient and ergonomic workflow. Support arms can be configured with a variety of degrees of freedom, including but not limited to x, y, z, pitch, roll, and yaw, and may also feature additional interface capabilities enabling height adjustment and movement.

[0153] An arm may consist of various numbers and types of joints and segments. Generally, an arm consists of at least two segments. Depending on the configuration, an arm may consist of three to five segments.

[0154] The arm may be configured to connect proximal to a main support base or base interface (e.g., robot, table, table / bed rail, cart, floor mount, etc.) and distally to a frame / assembly and the overall "UMC" or "coupling solution". This particular distal interface may further include the ability to control the position / orientation of the frame / assembly at the frame / assembly interface.

[0155] For example, in some embodiments, the arm / frame interface may include a ball-joint wrist. In another example, the interface may include the use of a gimbal wrist or an adjustable pitch and roll control wrist. These interfaces can be used in combination with specific user interfaces and inputs to assist interaction with various wrists. This may include additional handles or knobs (the examples are endless) to further facilitate the positioning of the UMC / coupling solution. For example, with a gimbal wrist, the frame / assembly benefits from having three degrees of freedom, including pitch, roll, and yaw adjustments (independent of the arm's degrees of freedom).

[0156] The support arm, equipped with an arm wrist and further connected to the frame / assembly, features functions such as brakes, including cable-operated or electronic brakes, and quick releases, which can interact with one or more axes individually or in groups. These may also include an electronic lifting system and base support. In some embodiments, these lifting systems / base supports are co-located with the robotic arm base, and the robotic arm is equipped with a tissue-disrupting therapy transducer configured to fit / operate within a sealed coupling solution. In other embodiments, the support arm is placed on a separate cart. In some cases, this separate cart may include a fluid control system or a user console. In other embodiments, it is connected to a bed / table (including, but not limited to, rails, sides, and the base of the bed / table). In other examples, it is connected to a floor structure / foundation that can accommodate weight and tipping requirements.

[0157] Fluid systems, control systems, and system architectures As part of overall fluid management, the tissue disruption system, including the acoustic / patient coupling system, may be configured to include an automated fluid system that primarily provides a reservoir for the preparation and use of the coupling medium, with preparation including degassing, cooling, monitoring, regulating, distributing / filling, and recovery / discharging functions of the coupling medium to the frame / assembly. The fluid control system may also include an emergency high-flow system for rapidly discharging the coupling medium from the UMC. In some embodiments, the fluid control system may be configured to use the coupling medium only once or to reuse the medium. In some embodiments, the fluid control system may utilize positive pressure or vacuum to perform leak testing of the UMC and membrane before filling with coupling medium. Vacuum assist may also be used to remove air from the UMC during the filling process. The fluid control system may further include filters configured to prevent particulate contaminants from reaching the UMC.

[0158] The fluid system can be implemented in the form of a mobile fluid cart. The cart may include an input tank, discharge tank, degassing module, filling pump, discharge pump, inert gas tank, air compressor, tubing / connectors / piping, electronic and manual control systems, input device, power supply, and one or more batteries. In some cases, the cart may also include a system check container / water tank for performance evaluation of the tissue disruption system and related system diagnostics (configured to accommodate the water volume and workspace required for the therapeutic transducer).

[0159] Histotripsy treatment planning software tools and systems Tissue ablation therapy is delivered by transmitting ultrasound signals from multiple transducer elements toward a common focal point. The pressure generated at this focal point induces cavitation in the target tissue, mechanically breaking, liquefying, or dissolving it. However, the efficiency and effectiveness of the treatment can be affected by many patient-specific factors, such as obstacles between the transducer array and the target tissue, and variations in intervening tissue between the transducer and the focal point (changes in tissue density, variations in tissue type, gas or air pockets, etc.). Considering the anatomical structure of the subject and the differences in body composition and constitution from subject to subject, creating an optimal acoustic window for a specific target site within the body can be extremely difficult.

[0160] This disclosure provides a treatment planning tool that can be implemented in software on one or more computing systems. In some embodiments, the treatment planning tool is implemented on the console of a tissue destruction system. In other embodiments, the treatment planning tool is implemented on a cloud or remote server or computing platform. The cloud or remote computing platform can communicate with the tissue destruction system / console. For example, a physician or healthcare professional can create and review a treatment plan on a first computing platform (such as a personal computer, smartphone, or tablet) and then transfer or transmit that treatment plan to the tissue destruction system console used for the actual tissue destruction procedure to execute the treatment plan.

[0161] Preoperative imaging, alignment, and evaluation

[0162] This specification provides a treatment planning tool for the treatment of histotripsy, which can be used to plan and support the treatment and procedures for histotripsy. The treatment planning tool disclosed herein can import and align preoperative images from various imaging methods (e.g., CT, CBCT, MRI, ultrasound, X-ray, etc.). Software and hardware located in the operating room, or remotely from the operating room / treatment site, can provide a treatment planning tool that can be configured to evaluate preoperative images and identify tissue targets such as tumors. While this specification describes preoperative imaging, in some embodiments, imaging can also be performed during tissue ablative surgery, and therefore, it should be understood that the procedures or techniques described herein can also be applied to real-time imaging or intraoperative imaging in addition to, or instead of, preoperative imaging.

[0163] In some embodiments, the treatment planning tool can use images of the patient when the patient is lying on the treatment table or positioned on the scanner gantry, which is the position the patient will take during the procedure. Furthermore, by positioning necessary preparatory instruments, gowns, clothing, and / or acoustic coupling containers on or around the patient, the most accurate medical images of the patient's body can be provided for the planned surgery. For example, the acoustic coupling containers described herein and used in tissue ablation therapy are large, rigid or semi-rigid containers placed on the patient and filled with an acoustic coupling medium (e.g., water) to enable acoustic coupling between the therapeutic transducer array and the patient's skin. In some cases, these acoustic coupling containers can be filled with 30 liters or more of liquid, which can be quite heavy and potentially compress, crush, or deform the patient's soft tissues. Therefore, it may be desirable to perform imaging preoperatively with the acoustic coupling container in place, so that any deformation observed during surgery can also be confirmed in the preoperative imaging. However, in some embodiments, this may not be practical or possible. Therefore, in some embodiments, the treatment plan is created based on preoperative images, and additional images can be acquired to identify deformation caused by the acoustic coupling vessel after the patient lies on the operating table and the acoustic coupling vessel is filled and placed in place. The system can be configured to align the preoperative images (the images on which the treatment plan is based) with the images deformed by the compression of the acoustic coupling vessel, and based on these deformations and alignments, the treatment plan, target tissue volume, and / or the pose and angle of the treatment head can be adjusted.

[0164] Referring to Figure 4A, the user interface (UI) screen 401a of the treatment planning user interface is shown. As described above, the treatment planning tool of this disclosure can be implemented as software on the console of a tissue destruction system, or in a remote computing environment such as the cloud or a personal device. Screen 401a is displayed to the user of the treatment planning tool on a display such as a monitor or television. In some embodiments, the screen is implemented as a graphical user interface (GUI), and the user can interact with the screen directly (e.g., via a touchscreen). In other examples, the user can operate the screen using peripheral input devices including, but not limited to, joysticks, computer mice, keyboards, touchpads, buttons, dials, knobs, or custom input devices.

[0165] In the illustrated embodiment, the UI screen 401a is divided into several sections, including a new treatment session section 403, a planned session setting section 405, and a data tools section 407. In the new treatment session section 403, users such as the treating physician or the treatment planning physician can enter credentials and identify whether the patient to be treated is a new patient 409 or a patient 411 who has recently or previously received treatment.

[0166] In the planning session setup section 405, the user can identify the organ to be treated at location 413. In the illustrated example, the user can choose either liver treatment or kidney treatment, but it is important to understand that any number of organs or treatment sites can be selected in this section of the UI screen, including the pancreas, spleen, prostate, bone, lung, heart, intestines, stomach, and brain. In some embodiments, the UI screen and subsequent workflow steps can be customized and tailored to the selected organ / site, depending on the organ / site being treated. For example, the treatment workflow for liver or liver tumors may differ from the treatment workflow for kidney or kidney tumors.

[0167] Furthermore, in the planning session setup section 405, the user can identify or select the treatment room configuration at location 415. In the illustrated example, location 415 offers a right-side configuration option (the histotripsy console is positioned to the right of the treatment table) and a left-side configuration option (the histotripsy console is positioned to the left of the treatment table). This section can also consider and provide other treatment room setups. These include treatment room setups with additional hardware and functions, including (but not limited to) other surgical systems and robots such as CBCT imaging, X-ray imaging, independent fluid management systems, or Intuitive Surgical's Da Vinci robotic surgery system.

[0168] Data Tools Section 407 provides users with access to medical images and records, including previously acquired medical images such as CBCT, CT, MRI, X-ray, and ultrasound images. Using Data Tools Section 407, users can import or export these images and access additional data and records as needed. Data accessible from Data Tools Section 407 can be stored locally, in the cloud, or on other devices such as portable hard drives.

[0169] When a new planning session is started with a selected patient, Figure 4B shows a UI screen 401b that displays a list of image sets available for use in the treatment planning process in the patient study section 422 to the user of the planning tool. In this example, two different image sets are available for the selected patient: a liver CT scan 417 and an abdominal CT scan 419. Section 421 of this example allows the user to view a preview of the image (in this case, the selected liver CT scan 419). Before proceeding to the treatment planning workflow, the user is prompted to confirm the appropriate image selection.

[0170] Figures 4C and 4D show the UI screens 401c and 401d, respectively. The new plan section 423 displays patient information and the selected image set. The plan session settings section 425 provides the user with selectable options for treatment planning, such as selecting an indication 427 from a dropdown menu and selecting the type of tissue or organ to be segmented by the treatment planning software in the segmentation section 429. The dropdown menu for indication 427 displays all the same options as for location 413 in the plan session settings section 405 described in Figure 4A. In this example, the kidney and liver are selectable options, but as mentioned above, other indications and treatment sites / organs are also envisioned.

[0171] Segmentation section 429 shows a non-exclusive list of organs that will be segmented in the image set, which in this example include the liver, kidneys, pancreas, spleen, prostate, bones, lungs, heart, intestines, and stomach. The segmentation process (described below) allows for the color-coding and application of other visually distinguishable segmentation to the selected tissues / organs on the selected medical images, making them easily identifiable to the user. Once the user has selected options in Adaptation 427 and Segmentation section 429, they can proceed to the next step in the treatment planning tool by operating the Planning Session Launch icon 431.

[0172] Figure 4E shows UI screen 401e after the planning session has been initiated using the adaptation and segmentation options selected by the user. In this example, UI screen 401e includes a patient information section 433 that provides relevant information such as patient name, age, date of birth, gender, and patient ID. The planning section 435 contains information about the current treatment plan, target organ, and surgeon. The patient setup section 437 contains information about the patient's setup and position on the operating table (such as rotation angle on the operating table, size and / or filling volume of the acoustic coupling vessel). In the illustrated example, the plan is based on the assumption that the patient is not rotated on the operating table (e.g., lying supine). If the orientation needs to be changed due to the location of the target tissue, this can be done by adjusting the slider or rotation value in section 437.

[0173] The image segmentation section 439 of the UI screen 401e shows how a selected indication or organ of interest 443 (e.g., liver) is segmented within an image set (e.g., liver CT 417 in Figure 4B) in one or more views (e.g., axial, sagittal, coronal). In some embodiments, segmentation may include highlighting or adding visual indicators to the segmented organs (e.g., color coding, contouring, contrast enhancement, or other techniques for presenting a portion of the segmented image to the user). For example, in one example, the segmented organs may be highlighted in a specific color such as blue, orange, or red. In other embodiments, the segmented organs may be surrounded by contour lines such as solid or dashed lines.

[0174] Furthermore, as shown in the image segmentation section 439 of UI401e, the system can identify and / or segment the target tumor or target tissue volume 445 within the selected organ. In some cases, the system can apply additional coloring, contouring, or contrast adjustments to the tumor or target tissue volume. In addition, as illustrated, the system can apply crosshairs or lines horizontally and / or vertically to locate the tumor or target tissue volume within the segmented organ.

[0175] Figure 4F shows an additional UI screen 401f for when a user of the treatment planning tool wants to incorporate additional image sets or segmentations into the treatment planning workflow. In this example, UI screen 401f returns to the menu displaying the patient examination section 422 (described in Figure 4B above). In the previous UI screen, the user selected a liver CT scan 417 for import and segmentation by the treatment planning tool. In Figure 4F, the user can select another image set, an abdominal CT scan 419, for use in the planning tool.

[0176] In the UI screen 401g of Figure 4G, if a different image set is selected, the system and UI screen may display to the user that the selected image set has a different coordinate system than previously imported images 447. This may be the result of various image sets being acquired along different cross-sections of the patient, such as the sagittal, coronal, or axial plane. For example, a liver CT scan 417 may be acquired in an axis plane higher (e.g., +) than the axis plane in which the abdominal CT scan 419 was taken, or vice versa. Because image sets may be in different coordinate systems, treatment plans that use multiple coordinate systems require the image sets to be aligned to a common coordinate system. If the user does not align the image sets, the treatment plan can be performed with only a single image set.

[0177] Figure 4H shows a UI screen 401h for segmenting a selected display 443 (e.g., liver) in the second image set. As described above, segmented organs can be colored, highlighted, have their contrast enhanced, or outlined. Furthermore, target tissue volumes or tumors 445 can also be displayed with coloring, highlighting, outlines, or enhanced contrast, and can be further identified on the image by crosshairs and horizontal and / or vertical lines.

[0178] Figure 4I shows the UI screen 401i with the first image set (liver CT scan 417) and the second image set (abdominal CT scan 419) aligned. As described above, the indication 443 and target tissue volume 445 can also be displayed on these aligned images.

[0179] Referring to Figure 4J, UI screen 401j gives the user the option to re-segment the selected display even after segmentation of one or more targets or organs has been performed. For example, in menu 449, "Segment Editing" allows segmentation of the aforementioned organs and targets, such as the liver, kidneys, pancreas, spleen, prostate, bones, lungs, heart, intestines, and stomach. Section 442 indicates that segmentation of the selected organ or tissue type is being processed.

[0180] Figure 4K shows UI screen 401k with the lung display 451 segmented within the image. Figure 4L shows UI screen 401l with the liver display 443, lung display 451, and bone display 453 segmented within the image. Figure 4M shows UI screen 401m, with the lung display 451, heart display 455, and custom segmentation 457 segmented and displayed in the image. In this example, custom segmentation 457 is an annotation, marking, or manual segmentation performed by a system user. For example, the user can circle or highlight a target tissue volume or tumor from a previous liver image in this set of images to confirm the tumor's location relative to other important structures or organs such as the lungs or heart.

[0181] Any of the treatment planning tools described herein can be used to generate and display a 3D digital model of a patient, and any medical images of the patient (such as CT, MRI, PET-CT, and any image fusion) can be included in, overlaid on, and aligned to the 3D model. The 3D model can include segmented target organs or tissues selected by the user or automatically selected by the software workflow for a specific treatment area. By segmenting the organs or tissues selected by the user, the user / physician can not only evaluate the location of the target tissue but also evaluate the adjacent tissue / organ structure.

[0182] Surgical instrument simulation

[0183] The treatment planning tools provided herein are configured to simulate the position and orientation of surgical instruments and systems relative to the patient, including therapeutic transducers and / or robotic arms, and acoustic coupling containers. Using the planning tools, a user or system can adjust or modify the position, orientation, and / or orientation of therapeutic transducers relative to the patient and / or acoustic coupling container to identify the optimal or preferred acoustic window for the therapeutic transducers relative to the target treatment site. The planning tools can use ray tracing and other simulation techniques to identify potential obstacles within the patient's body along the acoustic path of the therapeutic transducers. The user or system can use the planning tools to adjust the positions of therapeutic transducers, robotic arms, and acoustic coupling containers and identify potential collisions between the transducer array, robotic positioning arms, the patient, and other external structures such as acoustic coupling containers and other patient support structures like operating tables.

[0184] Referring to Figure 5, a UI screen 501 is shown that provides a graphical representation of one or more surgical instruments or structures related to an image of a patient containing a target tissue volume or tumor 545 (described above as the target tissue volume 445). In Figure 5, the image planning section 557 can provide various views of the segmented and aligned image set described above, as well as a graphical representation of the therapeutic transducer array 559 and / or additional surgical instruments or components (including, for example, an acoustic coupling container 561). In the illustrated embodiment, the image planning section 557 provides axial, sagittal, coronal, and 3D views, which can be selected by the user according to their preference.

[0185] The UI screen 501 may include a treatment head section 563 where the user can select a treatment head suitable for the target tissue volume 545 from a dropdown menu or the like. Various treatment heads are available for use in the tissue ablation treatment system, depending on the size, depth, or type of the target tissue. For example, smaller treatment heads are preferable for smaller or shallower targets, while larger treatment heads may be required for deeper tissue areas or areas hidden or obstructed by obstacles in bone or other tissues. Larger treatment heads can achieve higher energy levels, thus compensating for discrepancies or obstructions between the transducer and the target tissue volume. In some embodiments, the treatment head is automatically selected by the system based on the depth of the target tissue volume 545. For example, if the user selects the target tissue volume 545, the treatment planning tool can calculate the depth of the target tissue volume and automatically select a treatment head with a focal length appropriate for that depth. The type of acoustic coupling system / container may influence the selection of the treatment head. For example, certain anatomical structures may favor a coupling system that allows the treatment head to be placed closer to the patient's skin, while other anatomical structures may require the treatment head to be positioned further away. The type of coupling system used can affect the depth between the treatment head and the target tissue, and consequently, the type of treatment head that is appropriate for that treatment site.

[0186] In the target volume section 565, the user can adjust the size of the target tissue volume 545, including additional margins to be included in the treatment plan. The volume size can be adjusted in the X, Y, and Z directions at pre-selected intervals (e.g., increments of 0.1 mm or less).

[0187] In the treatment head angle section 567, the user can manipulate the position and orientation of the virtual treatment head and adjust it along numerous posture / angle parameters, including lateral, craniocaudal, and device roll adjustments. In some examples, as these parameters are adjusted, the graphical representation of the treatment transducer array 559 on the UI screen 501 moves in real time. In some embodiments, the position and / or orientation of the virtual treatment head becomes the starting point of the planned tissue destruction therapy. The coordinates of the posture / position of the simulated or virtual treatment head can be saved in the treatment plan. When the treatment plan is loaded into the tissue destruction system for actual treatment, the robotic arm and / or treatment head of the actual tissue destruction system are automatically positioned at the coordinates of the posture / position selected by the user during the treatment planning process.

[0188] In any embodiment described herein, the orientation / angle and / or position of the transducer array, as well as the size and margin of the target volume, can be stored in a predetermined treatment plan and transferred to the tissue ablative system for tissue ablative therapy. Once the treatment plan is loaded into the tissue ablative system, all user-selected items, including the orientation / position of the transducer array, the size and margin of the tissue volume, the type of treatment head, and other parameters described above, are automatically loaded into the tissue ablative console, enabling the system to deliver treatment according to the treatment plan.

[0189] Obstacle detection

[0190] As described above, bone or gas in the transducer beam path can block or bypass the transmission of acoustic energy from the target focal point, reducing the total amount of acoustic pressure generated. This can result in the generated acoustic pressure falling below the threshold for therapeutic effect or cavitation. Such obstructions can also pose a risk of thermal damage by creating hot spots in intervening tissue or increasing the amount of acoustic energy delivered to the tissue. Figure 6A shows an example of an ultrasound transducer array 602 positioned adjacent to the subject's skin. Each transducer element of array 602 can be directed towards a focal point within the subject, as indicated by the individual rays emitted from the array. The figure shows the presence of one or more obstructions, such as bone (ribs) or gas in the body, between the transducer and the focal point. These obstructions can hinder the propagation of acoustic energy to the focal point. For example, in Figure 6A, radiation 622a from the transducer reaches the focal point without obstruction, but radiation 622b from the transducer is blocked by one or more obstructions in the subject's body.

[0191] Changes in sound velocity along the propagation path of the transducer array's radiation can also affect where energy is deposited. For example, as shown in Figure 6B, when radiation passes through a boundary where the sound velocity changes, refraction can alter the angle and direction of the radiation. When ultrasound travels between two different media where the sound velocity increases, for example, at the boundary between water (bonding to the transducer) and soft tissue, the emitted sound waves tend to concentrate closer to the transducer than the transducer's geometric focus. This affects where subsequent boundary crossings occur and the location of local therapeutic effects. Understanding where the actual therapeutic focus is is crucial to deliver energy and cavitation to the target tissue and ensure that the entire target tissue is treated.

[0192] To address these issues, this disclosure provides intuitive, interactive visual, and quantitative feedback in the form of a user-oriented treatment planning tool for identifying the optimal or preferred acoustic window, transducer position, and orientation (posture). This includes systems and methods for visualizing the shadow of an obstruction as a projection onto the skin and / or transducer surface.

[0193] Ray tracing

[0194] Ray tracing can be used in some implementations of treatment planning tools to simulate how acoustic energy from a histotripsy transducer array travels through the patient's anatomical structures. As mentioned above, treatment planning tools can use high-resolution medical images (CT, CBCT, MRI, X-ray, etc.) and perform ray tracing on the medical image from a simulated treatment transducer array towards a focal or target tissue volume within the patient's body. Medical images can be taken of the patient before or during the procedure.

[0195] As an example, referring to Figure 7A, the light-emitting surface of a simulated transducer array 759 representing a tissue ablation therapy array is finely sampled by a series of equally spaced points, each point being the starting point of a ray 769 in the normal direction. These points can, for example, correspond to individual transducer elements of the transducer array. Each ray is tracked through a medical image of the patient or subject (such as a CT image) and tracked until it comes closest to a geometric focus located within or at the location of the target tissue volume 745, or until it terminates (for example, at an obstacle). As each ray travels along its path, patient image data is sampled from pre-treatment images (CT, MRI, etc.) to determine whether the boundaries of anatomical structures are detected. These structures can also be segmented before ray tracking (as described above) or, in the case of CT, identified by a Hounsfield value threshold.

[0196] As shown in Figure 7A, in one embodiment, the surface of the transducer can be sampled to provide a starting point for tracking the ray 769. Patient-specific volumetric medical images can be used to identify some or all of the tissue type, tissue density, and / or obstacles (e.g., bone, gas or air pockets, medical implants, etc.). Medical images include, for example, MRI or CT images of the subject, as described above. The radiation is irradiated perpendicular to the transducer surface and tracked through patient-specific volumetric images (usually CT or MR images) until it reaches the tissue boundary or obstacle. Rays passing through obstacles such as bone or gas (e.g., ray 769a) can be marked as obstacles by a visual indicator such as a colorimeter, or by other visual indicators such as contrast increases or decreases, highlighting, or contouring.

[0197] As described above, when a light ray passes through a structural boundary where the speed of sound changes, Snell's Law can be used to apply the refraction of the ray. In Figure 7A, ray tracing can be used to identify a ray passing through a boundary where the speed of sound changes and refracting according to Snell's Law. This generally means that the ray terminates not at the geometric focus, but at the point closest to the focus. When the speed of sound increases as the ray passes through a boundary (e.g., from water to soft tissue), the ray refracts and converges at a point closer to the transducer than the geometric focus. In non-invasive treatments, tissue-disrupting transducer arrays are typically placed outside the subject's body and acoustically coupled to the patient using a binding medium such as water, saline, or an acoustic binding gel. The sound velocity properties of the acoustic binding medium are known, and the sound velocity properties of the tissue are also generally known or can be approximately determined. Therefore, the interface or boundary between the binding medium and the subject's skin becomes a boundary where ray refraction can occur.

[0198] The results of the ray tracing procedure described above can be visualized in several useful ways within the treatment planning tool associated with the tissue destruction system. For example, a GPU-based ray tracing implementation enables interactive updates in response to transducer and patient movement, resulting in a smoother user experience. Ray tracing can be visualized only within the treatment planning environment, for example, by moving a simulated transducer during patient imaging, or it can be implemented in real time on the graphical user interface of the tissue destruction system while the patient is receiving or about to receive tissue destruction therapy.

[0199] In the example in Figure 7A, the system can display the ray path of a specific tissue-destroying transducer array (simulated or actual) in relation to the anatomical structures of the transducer and the patient. Ray color and other visual features, colors, or patterns can be used to indicate various characteristics such as obstacles and angles of incidence. For example, in the UI screen 701a of Figure 7A, ray 769 from the simulated transducer array 759 is displayed in a primary color such as green, indicating to the user that a specific transducer element of the array is reaching the target location without obstruction. As shown in the figure, the ray can be displayed as emitting from the transducer array 759, illuminating the patient's medical image or patient image, and terminating at the focal point or target tissue volume 745. Ray 769a, displayed in a different color such as red, indicates that the transducer element is blocked or obstructed. Other colors can also be used to convey information to the user. For example, yellow rays may indicate that a transducer element is partially blocked, or that rays refract due to changes in the speed of sound and do not pass through the geometric focus of the transducer array. Blue rays may be used to indicate air pockets or air-filled organs such as lungs. While the embodiments described above describe how color can be used to convey different types of tissue and defects, it is important to understand that other visual methods can also be used to convey the same information. For example, rays can be represented in grayscale, and the intensity of the ray can indicate how far the ray reaches the focus of the transducer array. Alternatively, the same information can be conveyed by using dashed lines, dots, or other patterns for the rays. In some cases, hybrid visualization can combine the ray path with a volume rendering of the defect structure, such as ribs.

[0200] The user interface may include additional visualization tools to assist the user in making decisions regarding transducer orientation angles and positioning during treatment planning. For example, a simple 2D view 771 of ray tracing data can be mapped to a 2D view of the transducer array surface to provide a useful heads-up display on the UI screen 701a. Figure 7B is a magnified view of the 2D view 771, showing rays mapped to the 2D view of the transducer array surface, and includes information on ray tracing analysis, including color-coded rays 769, 769a, and 769b representing unoccluded rays, occluded rays, and rays passing through gas pockets or other partial obstacles, respectively.

[0201] In some embodiments, the UI screen 701a may further provide a simple graph or meter 773 showing the relative amount of unobstructed or obstructed transducer elements, as shown in Figure 7C. This graph or meter 773 can be implemented in various ways, such as displaying it as a percentage or ratio of unobstructed to obstructed elements using color coding (e.g., green = most elements unobstructed, yellow = some elements obstructed, red = many elements obstructed), or simply counting or quantifying the number of unobstructed transducer elements (similar to a fuel gauge). This allows the user to be informed in real time which parts of the transducer array are obstructed, partially obstructed, or unobstructed. Furthermore, immediate feedback on the number or percentage of unobstructed / obstructed transducer elements can be obtained.

[0202] In the simulation environment described herein, the user can manipulate the position and orientation of the simulated transducer array 759 within the treatment head angle section 767 to find a more optimal acoustic window. For example, Figure 7D shows the initial orientation of the transducer array 759, where the 2D view 771 shows that most of the rays traced to the transducer surface are “green” or unshielded, with several “red” bands or patches corresponding to ribs or other obstructions to the transducer elements in the current orientation. In Figure 7E, a graph or meter 773 shows that most of the transducer elements (e.g., about 85%) are unshielded, and in this example, this information is conveyed in the form of a gauge 775 along with color coding. As mentioned above, color coding is just one implementation example, but it should be understood that this information can be conveyed in various ways, such as displaying the percentage, actual value, or number of shielded and unshielded transducer elements. As shown in Figure 7F, a 2D view of the back-projected rays can also be displayed on the simulated transducer array 759.

[0203] Referring to Figure 8A, the UI screen 801a shows an intuitive display of a 2D view 871 of the back-projected rays, which can also be projected as a volume rendering 877 onto a simulated model of the patient's skin by displaying the properties of the rays at the point where they cross the water / skin boundary. When collisions with obstacles are displayed in different colors, the user can be provided with an interactive "X-ray" view of anatomical structures to be avoided when manipulating the transducer's orientation. Here again, the GPU implementation in the tissue destruction system console enables this visualization to be displayed with smooth interaction.

[0204] The software and corresponding UI display may include both a simulated model of the ray properties on the patient's skin or surface, and corresponding models of occluded, unoccluded, and partially occluded rays on the transducer surface. Since these two surfaces are displayed as mirror images of various rays, as the movement of the transducer over the patient is simulated, the occluded, unoccluded, and partially occluded rays change on the UI not only on the patient surface but also on the transducer surface. The optimal transducer orientation is obtained (and recorded) by aligning the transducer with the patient to minimize acoustic interference, as described herein. In this example, the position of the acoustic coupling vessel 861 relative to the patient is also shown.

[0205] By combining volume rendering of the patient's anatomical structure, in some embodiments, the planning tool and / or tissue dissection system can be configured to reveal or display the deep structures within the subject's body. Referring to Figures 8A–8B, an example of this skin projection technique is shown in combination with a 3D skin surface. The volume rendering 877 can be adjusted so that soft tissue is cut off in combination with an oblique planar view of the source image data volume. The simple 2D view 871 described above can also be displayed along with the 3D view of the obstruction projection of the skin surface. In some embodiments, the volume rendering 877 can be displayed simultaneously with the 2D view 871 and the aforementioned graph or meter 873 to show the number or percentage of occluded transducer elements. Alternatively, the user can select the view to display before or during the procedure. Combined with an interactive 3D display, the user can receive interactive feedback to find the transducer position with the most optimal acoustic window for the target.

[0206] To assist in treatment planning, additional system functions or components can be optionally displayed. For example, referring to Figures 8A–8B, the user can choose to display the acoustic coupling container 861 over a simulated patient (or image of a patient). In Figures 8C–8F, the user can choose to display the simulated transducer array 859. As described herein, the coupling container provides acoustic coupling between the transducer array and the patient, defining a volume or space in which the transducer array and the robotic positioning arm can move during a particular procedure. Displaying this coupling container over the planned treatment area helps to identify where the simulated transducer array can move, or optionally to identify a more optimal patient posture or coupling container placement based on the results of ray tracing for a particular treatment plan.

[0207] Furthermore, this planning tool can be used to identify potential collisions between system components (e.g., between robots / transducers and coupling containers) and collisions between system components and patients. For example, Figure 8E shows a simulation example of a collision 879 between a transducer array 859 and a patient. This collision can be represented by color or other visual indicators as described above. In some embodiments, collisions can be represented by simulating how much force is applied during the collision. For example, in certain treatments, some degree of collision or force application from the transducer to the patient may be acceptable. The amount and degree of the applied force can also be represented by visual indicators as described herein (e.g., red indicates a large force, yellow indicates an acceptable force, and green indicates no force or collision). Similarly, in Figure 8F, the simulation or planning tool can display a collision 881 between a transducer array and a coupling container. In this example, it is shown as the transducer array encroaching on or passing through the boundary of the coupling container.

[0208] By employing any of the above technologies, the treatment planning tool of this disclosure can provide interactive functionality that allows the user to digitally manipulate or change the position / orientation of a graphical representation of an ultrasound treatment head / transducer array within the context of a selected target in the patient. By manipulating the position / orientation of the virtual treatment head, the user can identify the optimal acoustic window to the target. This is because the treatment planning tool can provide real-time information about obstacles such as bone and gas between the treatment head and the target as the position / orientation changes. The treatment planning tool can also detect occlusion or partial obstruction.

[0209] The ability to visually display occlusions allows users to identify the optimal position / orientation of the target. The optimal position / orientation of the treatment head can be digitally saved within the treatment plan, so that when the patient is lying on the treatment table during the actual treatment procedure, the treatment plan can be used to guide the physician to the optimal position / orientation, or the robotic arm can be automatically instructed to position the treatment head in the optimal orientation / position at the start of treatment based on the treatment plan.

[0210] Aberration correction

[0211] The acoustic output of a transducer array reaches its geometric focus in a time equal to the path length of the light ray from the transducer to the focal point divided by the speed of sound along that path. When passing through multiple media with different speeds of sound, the total flight time is the sum of the path lengths of all media divided by their respective speeds of sound. At the surface of the transducer, if the path length through a particular medium changes, the arrival time also changes. This causes a phenomenon called phase aberration, which leads to destructive interference. As a result, the focal position generally shifts and the amplitude decreases.

[0212] A transducer array consisting of a sufficient number of independent sub-transducer elements whose outputs can be independently controlled may be able to correct for phase aberration by estimating the time delay of each element so that their signals arrive at the desired focal point simultaneously. One method for calculating these delay values ​​is to use the ray tracing method described above. For each ray in the transducer array, the time delay required to reduce phase aberration is calculated using the path length through the coupling medium and soft tissue and the estimated velocity of sound. The effects of phase aberration can be reduced by estimating or simulating the propagation time from different transducer elements to the focal point and applying the appropriate time delay to the ultrasonic emission for the appropriate transducer element. This restores the peak to the geometric focal position and increases the amplitude.

[0213] In one embodiment, this can be achieved by fusing preoperative images with intraoperative ultrasound and aligning the preoperative image with the actual orientation of the transducer. By using ray tracing, the delay value for each element can be estimated from the preoperative image, and phase aberration can be reduced. This correction can be used independently or as the initialization of a phase aberration correction method based on subsequent measurements. Efficient aberration correction improves treatment accuracy and expands the treatment range.

[0214] Pressure simulation

[0215] Furthermore, the planning tools provided herein are configured to perform pressure simulations on specific acoustic target locations and / or target treatment volumes within a 3D digital model of the subject, determine the optimal drive voltage required to generate cavitation at specific treatment locations, and simulate and predict aberration correction algorithms that may be required as a result of obstacles or tissue changes. The treatment planning tools provided herein can optimize specific tissue ablation therapies, and by selecting the optimal acoustic window, the cavitation initiation threshold in the target tissue volume can be reduced by up to 30–50%, improving the energy transfer efficiency of the system.

[0216] Interactive pressure field simulations are useful for predicting the feasibility and quality of treatments for specific targets. Based on the ray tracing method described above, high-speed GPU-accelerated pressure simulations can be achieved by calculating the Rayleigh-Sommerfeld integral in a 2D or 3D computational domain using the pre-calculated shape of the traced rays. In this way, the sum of the complex contributions of all rays (usually thousands) can be calculated in parallel for each point in the target domain. With appropriate current hardware, an interactive update rate of 5-10 Hz can be achieved in a 100x100 point 2D field when considering approximately 15,000 traced rays.

[0217] The calculated two-dimensional pressure field can be displayed in color along with amplitude and real signal value plots obtained from the vertical centerline of the two-dimensional field. Both continuous and pulsed wave emissions from the transducer can be simulated by applying variable time and space windows to the contribution of each traced ray to the result. All of this information can be displayed to the system user during treatment.

[0218] The planning tools provided herein can use ray tracing from a virtual tissue ablation transducer array to a 3D digital model of the patient to estimate one or more drive voltages for the virtual tissue ablation transducer array required to generate cavitation within the target tissue volume for a specific orientation / position of the virtual tissue ablation transducer array. Because the user can manipulate the position / orientation of the virtual array, the treatment planning tool can iterate through pressure simulations until it finds an array position / orientation that yields efficient cavitation generation at a voltage level acceptable to the user. The user can repeat the operation of changing the array position / orientation and running pressure simulations to find the optimal array position / orientation. The optimal position / orientation and estimated drive voltages are saved in the digital treatment plan and can be used later during treatment.

[0219] Quality assessment of treatment plans

[0220] The high-speed pressure simulation function allows for the interactive collection of quantitative treatment planning quality indicators. The acoustic pressure generated by the transducer typically varies across the entire range of the defined treatment volume. As the transducer moves to focus on different points within the treatment volume, the beam path through intervening tissue changes accordingly, altering the tissue's acoustic properties that adjust the focal amplitude. These variations may result in focal pressure amplitudes below the bubble cloud formation threshold in certain areas of the treatment region, indicating that the transducer output needs to be increased in those areas. Such output calibration adjustments limit user manual input to investigating seven points (the center point and the endpoints of each direction), where the user adjusts the voltage to generate cavitation. User input is interpolated across the entire treatment region. Pressure simulation automates this process, enabling more thorough region sampling. Furthermore, treatment planning quality can be communicated interactively to the user in a manner similar to a dose-volume histogram of the target region (and, if necessary, the surrounding reserve region). Creating a volume-rendered treatment quality map can also provide a 3D context to the planned volume.

[0221] Therefore, in one embodiment, a pretreatment planning technique can be used that utilizes pressure simulation to determine a pressure threshold across the entire target tissue volume. Once a treatment plan is created for the target tissue volume and multiple treatment locations are defined, pressure simulation can be used to determine the cavitation threshold and / or drive voltage / amplitude of the transducer array for some or all of the multiple treatment locations. Furthermore, by using pressure simulation in a given treatment area, the amount of heating of the body wall can be estimated, and the total treatment time, taking into account the cooling time required during treatment, can be estimated. Subsequently, treatment can be carried out according to the proposed treatment plan based on the drive voltage determined by the pressure simulation.

[0222] It should be understood that features relating to one embodiment described herein can be substituted or combined with features relating to other embodiments.

[0223] When a feature or element is described as "on top of" another feature or element, it may be directly on the other feature or element, or there may be an intervening feature and / or element. In contrast, when a feature or element is described as "directly on top of" another feature or element, there is no intervening feature or element. Also, when a feature or element is described as "connected," "attached," or "joined" to another feature or element, it should be understood that it may be directly connected, attached, or joined to the other feature or element, or there may be an intervening feature or element. In contrast, when a feature or element is described as "directly connected," "directly attached," or "directly joined" to another feature or element, there is no intervening feature or element. Features and elements described or illustrated, even if described or illustrated in relation to one embodiment, are applicable to other embodiments. Also, those skilled in the art will understand that a reference to a structure or feature positioned "adjacent" to another feature may have portions that overlap with or are located beneath the adjacent feature.

[0224] The terms used herein are for the purpose of describing specific embodiments and do not limit the invention. For example, the singular forms “a,” “an,” and “the” as used herein also include the plural form unless otherwise clearly indicated in the context. It will be further understood that the terms “including” and / or “including” as used herein indicate the presence of the described features, procedures, operations, elements, and / or components, and do not exclude the presence or addition of one or more other features, procedures, operations, elements, components, and / or groups thereof. The terms “and / or” as used herein include any combination of one or more of the items described herein and may be abbreviated as “ / ”.

[0225] As shown in the diagram, spatially relative terms such as “below,” “downward,” “low,” “up,” and “high” may be used herein to describe the relationship between one element or feature and another, in order to facilitate explanation. Spatially relative terms should be understood as intended to encompass various orientations of the device during use or operation, in addition to the orientation shown in the diagram. For example, if the device in the diagram is inverted, an element described as “below” or “below” another element or feature would be positioned “above” the other element or feature. Therefore, the expression “below” may encompass both upper and lower positional relationships. The device may also be installed in other orientations (rotated 90 degrees, or otherwise), and the spatially relative descriptors used herein shall be interpreted accordingly. Similarly, terms such as “upward,” “downward,” “vertical,” and “horizontal” are used herein for descriptive purposes only, unless otherwise specified.

[0226] In this specification, the terms “first” and “second” may be used to describe various features / elements (including steps), but unless otherwise specified in the context, these features / elements should not be limited by these terms. These terms can be used to distinguish one feature / element from another. Thus, the first feature / element described below may also be called the second feature / element, and similarly, the second feature / element described below may also be called the first feature / element, without departing from the teachings of the present invention.

[0227] Throughout this specification and the subsequent claims, unless otherwise specified in the context, the word “includes” and variations such as “includes” and “includes” mean that various components can be used together in a method and article (e.g., including compositions and apparatus, apparatus and methods). For example, the term “includes” is understood to mean that an explicitly stated element or procedure is included, but not that other elements or procedures are excluded.

[0228] In this specification and in the claims, unless otherwise explicitly stated, all numerical values, including in the examples, can be read as being preceded by the words “about” or “approximately,” even if the words are not explicitly present. The words “about” or “approximately” can be used to indicate that the described value and / or location falls within a reasonably expected range of values ​​and / or locations when describing size and / or location. For example, a numerical value may have values ​​such as ±0.1%, ±1%, ±2%, ±5%, ±10% of the stated value (or range of values). Unless otherwise specified in the context, numerical values ​​described herein should be understood to include values ​​near or approximate to that value. For example, if the value “10” is disclosed, “about 10” is also disclosed. Numerical ranges described herein include all subranges contained within that range. Furthermore, if a value is disclosed, it should be understood that possible ranges less than or equal to that value, greater than or equal to that value, and between values ​​are also disclosed, which is a reasonable understanding for those skilled in the art. For example, if a value "X" is disclosed, then "less than or equal to X" and "greater than or equal to X" (for example, if X is a number) are also disclosed. Furthermore, throughout the application, data is provided in various formats, and this data is understood to represent endpoints, starting points, and ranges for any combination of data points. For example, if a specific data point "10" and a specific data point "15" are disclosed, then values ​​greater than 10 and 15, greater than or equal to 10, less than 10, less than or equal to 10, equal to 10 and 15, and values ​​between 10 and 15 are considered disclosed. Also, each value between two specific values ​​is considered disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also considered disclosed.

[0229] Preferred embodiments of the present invention have been shown and described herein, but it will be clear to those skilled in the art that these embodiments are provided merely as examples. Those skilled in the art will be able to conceive of numerous variations, modifications, and substitutions without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein can be used in carrying out the present invention. The following claims define the scope of the present invention, and the methods and structures included in these claims, as well as their equivalents, are intended to be encompassed thereby.

Claims

1. A method for planning histotripsy therapy, A step of obtaining at least one diagnostic image of the subject, including the location of the target tissue; A step of generating a three-dimensional (3D) digital model of the location of the subject and the target tissue from the at least one diagnostic image; The steps of: positioning a virtual histotripsy therapy transducer array near the 3D model and positioning the geometric focus of the virtual histotripsy therapy transducer on or near the location of the target tissue in the 3D digital model; The steps include sampling the virtual histotripsy therapy transducer array to provide multiple starting points for rays corresponding to the simulated ultrasonic energy supplied by the transducer elements of the virtual histotripsy therapy transducer; A step of tracking the plurality of light rays through the 3D digital model; A step of identifying one or more shielded or partially shielded transducer elements of the virtual histotripsy therapy transducer array that correspond to light rays passing through obstacles in the 3D digital model; A method of having.

2. The method further includes the step of displaying to the user the light rays passing through the obstacle. The method according to claim 1.

3. The method further includes the step of providing a first graphical representation of a ray passing through an obstacle and a second graphical representation of a ray not passing through an obstacle. The method according to claim 1.

4. Light rays passing through obstacles are displayed in the first color, and light rays not passing through obstacles are displayed in the second color. The method according to claim 3.

5. The 3D digital model further includes a skin surface model of the subject, The method according to claim 1.

6. The method further includes the step of displaying a map of light rays passing through obstacles on the skin surface model. The method according to claim 5.

7. The step of displaying light rays passing through an obstacle includes the step of providing a two-dimensional view of the plurality of light rays. The method according to claim 2.

8. The above method further, A step of receiving input for adjusting the position or orientation of the virtual histotripsy therapy transducer; The steps include: resampling the virtual histotripsy therapy transducer array to provide a plurality of starting points for second rays corresponding to the simulated ultrasonic energy irradiated by the transducer elements of the virtual histotripsy therapy transducer array; A step of tracking the plurality of second rays through the 3D digital model; Steps include identifying one or more shielded or partially shielded transducer elements of the virtual histotripsy therapy transducer array that correspond to light rays passing through obstacles in the 3D digital model; Having, The method according to claim 1.

9. The method further comprises the step of generating a digital treatment plan including the location of the target tissue and the orientation or position of the virtual histotripsy therapy transducer array. The method according to claim 1.

10. The aforementioned digital treatment plan further includes the depth and size of the location of the target tissue. The method according to claim 1.

11. The method further comprises the step of segmenting one or more target tissues or organs that are close to the location of the target tissue. The method according to claim 1.

12. A method for planning histotripsy therapy, A step of obtaining at least one diagnostic image of the subject, including the location of the target tissue; A step of generating a three-dimensional (3D) digital model of the location of the subject and the target tissue from the at least one diagnostic image; The steps of: positioning a virtual histotripsy therapy transducer array near the subject and positioning the geometric focus of the histotripsy therapy transducer on or near the location of the target tissue; The steps include sampling the virtual histotripsy therapy transducer array to provide multiple starting points for rays corresponding to the ultrasonic energy supplied by the transducer elements of the virtual histotripsy therapy transducer array; In the 3D digital model, the step of tracking the plurality of rays passing through the tissue boundary; A step of identifying the angle of refraction of one or more light rays that pass through the tissue boundary from a first sound medium and enter a second sound medium; A method of having.

13. The method further includes the step of showing the user the angle of refraction of the light ray. The method according to claim 12.

14. The method further includes the step of displaying the angle of refraction of the light ray to the user. The method according to claim 12.

15. The method further comprises the step of displaying the expected focal point of the light ray based on the angle of refraction. The method according to claim 12.

16. The method further comprises the step of displaying a skin surface model of the subject, including a map of the light rays affected by the angle of refraction. The method according to claim 12.

17. The method further comprises the step of providing a two-dimensional representation of the light ray. The method according to claim 12.

18. The method further comprises the step of dividing the path length of each ray into a plurality of segments having known sound speeds. The method according to claim 12.

19. The method further includes the step of calculating the time delay until each ray reaches the geometric focus. The method according to claim 18.

20. The method further comprises the step of adjusting the timing of ultrasound irradiation in multiple transducer elements of the histotripsy therapy transducer based on the calculated time delay. The method according to claim 19.

21. A method for planning histotripsy therapy, A step of obtaining at least one diagnostic image of the subject, including the location of the target tissue; A step of generating a three-dimensional (3D) digital model of the location of the subject and the target tissue from the at least one diagnostic image; The steps of: positioning a virtual histotripsy therapy transducer array near the subject and positioning the geometric focus of the histotripsy therapy transducer array on or near the location of the target tissue; The steps include sampling the histotripsy therapy transducer to provide multiple starting points for rays corresponding to the ultrasonic energy supplied by the transducer elements of the histotripsy therapy transducer array; A step of tracking the plurality of light rays through the 3D digital model; A step of generating a pressure simulation in the 3D digital model based on the plurality of light rays; A step of estimating one or more drive voltages of the virtual histotripsy therapy transducer array necessary to generate cavitation at the location of the target tissue, based on the pressure simulation; A method of having.

22. The step of generating the pressure simulation further includes calculating the Rayleigh-Sommerfeld integral on a two-dimensional or three-dimensional computational domain. The method according to claim 21.

23. The method further includes the step of displaying a ray of light that penetrates an obstacle and reaches the user. The method according to claim 21.

24. The method further comprises the steps of providing a first graphical representation of a ray passing through an obstacle and providing a second graphical representation of a ray not passing through an obstacle. The method according to claim 21.

25. Light rays passing through obstacles are displayed in the first color, and light rays not passing through obstacles are displayed in the second color. The method according to claim 24.

26. The 3D digital model further includes a skin surface model of the subject, The method according to claim 21.

27. The method further includes the step of displaying a map of light rays passing through obstacles on the skin surface model. The method according to claim 26.

28. The step of displaying light rays passing through an obstacle further comprises the step of providing a two-dimensional view of the plurality of light rays. The method according to claim 23.

29. The above method further, A step of receiving input for adjusting the position or orientation of the virtual histotripsy therapy transducer; The steps include: resampling the virtual histotripsy therapy transducer array to provide a plurality of starting points for second rays corresponding to the simulated ultrasonic energy irradiated by the transducer elements of the virtual histotripsy therapy transducer array; A step of tracking the plurality of second rays through the 3D digital model; Steps include identifying one or more shielded or partially shielded transducer elements of the virtual histotripsy therapy transducer array that correspond to light rays passing through obstacles in the 3D digital model; Having, The method according to claim 21.

30. The method further comprises the step of generating a digital treatment plan including the location of the target tissue and the orientation or position of the virtual histotripsy therapy transducer array. The method according to claim 21.

31. The aforementioned digital treatment plan further includes the depth and size of the location of the target tissue. The method according to claim 21.

32. The method further comprises the step of dividing one or more target tissues or organs located near the location of the target tissue. The method according to claim 21.

33. It is an ultrasonic system, Robot positioning system; An ultrasonic transducer array disposed on the robot positioning system, wherein the ultrasonic transducer array is configured to irradiate a subject with ultrasonic pulses; A diagnostic imaging system configured to acquire preoperative images of the subject; display; One or more processors operably connected to the robot positioning system, the diagnostic imaging system, the ultrasonic transducer array, and the display; A non-transient computing device-readable medium storing instructions for generating an ultrasound treatment plan, wherein, when the instructions are executed by one or more processors, the ultrasound system A step of using the diagnostic imaging system to acquire at least one diagnostic image of the subject, including the location of the target tissue; A step of generating a three-dimensional (3D) digital model of the location of the subject and the target tissue from the at least one diagnostic image; The steps include positioning an ultrasound transducer array near the subject and positioning the geometric focus of the pseudo-tripsy therapy transducer on or near the location of the target tissue; The steps include sampling the ultrasonic transducer array to provide multiple starting points for rays corresponding to the ultrasonic energy supplied by the transducer elements of the ultrasonic transducer; A step of tracking the plurality of light rays through the 3D digital model; A step of identifying one or more occluding rays corresponding to rays passing through an obstacle within the subject; A step of displaying the plurality of light rays and the one or more shielded light rays superimposed on the 3D digital model; To have it implemented system.

34. Blocked light rays are displayed in the first color, and unblocked light rays are displayed in the second color. The system according to claim 33.

35. When the instruction is executed by the one or more processors, it causes the ultrasound system to perform the step of displaying a 3D model of the subject's skin surface, including a map of the shielded rays. The system according to claim 33.

36. When the instruction is executed by the one or more processors, it causes the ultrasonic system to perform the step of providing a two-dimensional image of the shielded light rays. The system according to claim 33.

37. This is a therapy planning tool for histotripsy. display; User interface; One or more processors operablely connected to the display and the user interface; A non-temporary computing device read medium storing instructions for generating a treatment plan for ultrasound therapy, wherein the instructions are executed by one or more processors, A step of receiving one or more diagnostic images of a subject, including the location of the target tissue; A step of displaying a three-dimensional (3D) model on the display showing the positions of the subject and the target tissue; A step of displaying a virtual ultrasound treatment transducer array near the 3D model of the subject; Steps include receiving input from the user interface, including instructions for changing the orientation or position of the virtual ultrasound therapeutic transducer array; A step of simulating multiple rays from the virtual ultrasound therapeutic transducer array in a given posture and position to the 3D model of the subject and to the location of the target tissue; A step of displaying information on a display indicating whether any of the plurality of light rays passes through an obstacle in the 3D model of the subject; To implement A therapy planning tool for histotripsy.

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