Systems and methods for robot-assisted histotripsy targeting based on pre-treatment MRI / CT scans

Abstract

Methods and devices are provided for generating cavitation in tissue. Methods and devices are also provided for surgical guidance, including defining a target treatment zone and guiding the focal point of a treatment transducer to the target treatment zone. Embodiments are provided for interregistering multiple surgical imaging and guidance systems. Systems for performing histotripsy procedures are also discussed.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 958,209, filed January 7, 2020, entitled "Systems and Methods for Robotically-Assisted Histotripsy Targeting Based on MRI / CT Scans Taken Prior to Treatment," which is incorporated herein by reference.

[0002] (Statement regarding federally funded research) This invention was made with Government support under NS108042 awarded by the National Institutes of Health. The Government has certain rights in the invention.

[0003] (Incorporated by reference) All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0004] This disclosure details novel high intensity therapeutic ultrasound (HITU) systems configured to generate acoustic cavitation, and methods, devices, and procedures for minimally or non-invasive treatment of healthy, diseased, and / or damaged tissue. The acoustic cavitation systems and methods described herein, also referred to as histotripsy, may include transducers, drive electronics, positioning robots, imaging systems, and integrated treatment planning and control software to provide comprehensive treatment and manipulation to a patient's soft tissue. [Background technology]

[0005] Histotripsy, or pulsed ultrasound cavitation therapy, is a technique in which extremely short and intense bursts of acoustic energy induce controlled cavitation (microbubble formation) in a focal mass. The vigorous expansion and implosion of these microbubbles mechanically homogenize the cellular and tissue structures of the focal mass, an end result that is significantly different from the coagulation necrosis characteristic of thermal ablation. Operation in the field of non-thermal histotripsy requires the delivery of acoustic energy in the form of high amplitude acoustic pulses with low duty cycles.

[0006] Compared to conventional focused ultrasound techniques, histotripsy has important advantages: 1) the destruction process at the focal point is mechanical, not thermal; 2) the cavitation appears bright on ultrasound images, confirming accurate targeting and localization of the treatment; 3) the treated tissue typically, but not always, appears darker (more hypoechoic) on ultrasound imaging, allowing the surgeon to see the treatment site; 4) histotripsy creates the lesion in a controlled and precise manner. It is important to emphasize that unlike thermal ablation techniques such as microwave, radiofrequency, and high intensity focused ultrasound (HIFU), histotripsy relies on the mechanical action of cavitation for tissue destruction. Summary of the Invention

[0007] The present invention has been made to solve the problems in the conventional techniques described above. [Means for solving the problem]

[0008] Receiving a first image of the target tissue mass in a surgical guidance system, acquiring a second image of the target tissue mass with the surgical guidance system, and matching the first image with the second image in the surgical guidance system. Alignment determining boundary coordinates of the target tissue mass in the first image by using the surgical guidance system; determining focal coordinates of a focal point of a histotripsy transducer by a surgical guidance system; and determining translation coordinates in the surgical guidance system to set the focal point of the histotripsy transducer within the boundary coordinates of the target tissue mass in the first image. decisionand moving the histotripsy transducer focal point based on the translation coordinates to establish the histotripsy transducer focal point within the target tissue mass.

[0009] In some implementations, the moving step further includes moving the histotripsy transducer with a robotic positioning system. Alternatively, the moving step further includes electronically steering the histotripsy transducer focal point.

[0010] In one implementation, the first image comprises a high resolution image from an advanced diagnostic medical imaging system, such as a high resolution MRI image, a high resolution CT image, a cone beam CT image, or an enhanced fluoroscopic image.

[0011] In other implementations, the second image includes an ultrasound image, a photograph, or an optical image.

[0012] In some implementations, Alignment The steps further include identifying standard regions in both the first image and the second image, and correlating a coordinate system of the first image with a coordinate system of the second image using the standard regions.

[0013] In another implementation, determining the focal coordinates further includes setting a fiducial marker on the histotripsy transducer and determining the fiducial marker with a surgical guidance system.

[0014] In one implementation, the method further includes defining a treatment margin for the target tissue mass, calculating a 3D grid region covering the target tissue mass and the treatment margin, and displaying the 3D grid region on the first or second image. In another example, the treatment margin includes a positive treatment margin that extends outside the target tissue mass. In some implementations, the treatment margin includes a negative treatment margin that extends into the target tissue mass.

[0015] In many implementations, the method further includes applying a histotripsy procedure to the target tissue mass.

[0016] In some implementations, the method further includes imaging the histotripsy procedure and detecting a difference between the first image and the second image. Alignment and updating the intraoperative

[0017] In one implementation, the method further includes generating a histoablation treatment map and overlaying the histoablation treatment map on the first or second image in real time.

[0018] In some examples, the robotic positioning system can move the histotripsy transducer in three degrees of freedom, while in other examples, the robotic positioning system can move the histotripsy transducer in six degrees of freedom.

[0019] In one embodiment, the moving step further includes a combination of electronically steering the histotripsy transducer focal point and moving the histotripsy transducer with a robotic positioning system.

[0020] In various implementations, the target tissue mass may include a tumor, a blood clot, an organ, or a brain hemorrhage.

[0021] Inserting an acoustic detector into tissue within or near the target tissue mass, determining the location of the target tissue mass relative to a focal point of a histotripsy transducer with the acoustic detector, and calculating translation coordinates necessary to set the focal point of the histotripsy transducer within the target tissue mass. decision Another method of surgical guidance is also provided, comprising:

[0022] In some embodiments, the method further comprises applying a histotripsy procedure with a histotripsy transducer.

[0023] In one implementation, the inserting step further includes inserting a catheter into tissue in or near the target tissue mass, the catheter including an acoustic detector, hi another implementation, the inserting step further includes inserting a needle into tissue in or near the target tissue mass, the needle including an acoustic detector.

[0024] Inserting a fiducial marker into tissue in or near the target tissue mass, determining the location of the target tissue mass relative to a focal point of a histotripsy transducer using the fiducial marker, and calculating translation coordinates required to set the focal point of the histotripsy transducer within the target tissue mass. decision A method of surgical guidance is provided that includes:

[0025] In some embodiments, the method further comprises applying a histotripsy procedure with a histotripsy transducer.

[0026] A surgical system is provided that includes a surgical guidance system including a first imaging system and a second imaging system, a robotic positioning arm, a histotripsy treatment transducer coupled to the robotic positioning arm, and an electronic controller operatively coupled to the first imaging system, the surgical guidance system, the second imaging system, the robotic positioning arm, and the histotripsy treatment transducer, the electronic controller operable to combine a first image of the target tissue mass from the first imaging system with a second image of the target tissue mass from the second imaging system. Alignment and the electronic controller is further configured to determine the coordinates of the movements of the robotic positioning arm required to set the focal point of the histotripsy transducer within the target tissue. decision The device is configured to: [Brief description of the drawings]

[0027] The novel features of the invention are set forth with particularity in the following claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description, when taken in conjunction with the accompanying drawings, which set forth illustrative embodiments, in which the principles of the invention are utilized. [Figure 1A] ~ [Figure 1B] 1 illustrates an ultrasound imaging and treatment system. [Diagram 2] 1 is a flow chart illustrating one method of guiding a surgical procedure using a tissue disruption system. [Diagram 3] 1 is an example of a stereotactic histotripsy treatment system. [Figure 4A] ~ [Figure 4C] 1 illustrates a method for performing stereotactic histotripsy. [Diagram 5] 13 is a flow chart illustrating another method of guiding a surgical procedure using a tissue disruption system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] The disclosed systems, methods, and devices may be used for minimally or non-invasive acoustic cavitation and treatment of healthy, diseased, and / or damaged tissue, including those incorporated into extracorporeal, percutaneous, endoscopic, laparoscopic, and / or robotic medical systems and procedures. As described below, the acoustic cavitation system may include various subsystems, including carts, procedures, integrated imaging, robotics, connections, and software. The system may also include various other components, accessories, and equipment, including, but not limited to, computers, cables and connectors, networking devices, power supplies, displays, drawers / storage, doors, wheels, and various simulation and training tools. All systems, methods, and means for performing / controlling / achieving tissue disruption are considered part of this disclosure, including any new related inventions disclosed herein.

[0029] 1A generally illustrates a histotripsy system 100 according to the present disclosure including a treatment transducer 102, an imaging system 104, a display and control panel 106, a robotic positioning arm 108, and a cart 110. The system may further include an ultrasound coupling interface and a coupling medium source, not shown.

[0030] 1B is a bottom view of the treatment transducer 102 and imaging system 104. As shown, the imaging system may be located at the center of the treatment transducer. However, other embodiments may include an imaging system located elsewhere within the treatment transducer or integrated directly into the treatment transducer. In some embodiments, the imaging system is configured to provide real-time imaging at the focal point of the treatment transducer.

[0031] The histotripsy system may include one or more of a variety of subsystems, including a treatment subsystem capable of performing, applying, focusing, and achieving acoustic cavitation / hisotripsy through one or more treatment transducers, an integrated imaging subsystem (or connectivity thereto) that allows real-time visualization of the treatment site and histotripsy throughout the procedure, a positioning subsystem that allows mechanical and / or electronic steering of the treatment transducer and further connection / support or interaction with the coupling subsystem to allow acoustic coupling between the treatment transducer and the patient, and software that communicates, controls, and interconnects with the system and a computer-based control system (and other external systems), as well as various other components, accessories, and equipment, including one or more user interfaces and displays and associated guided workflows, all of which function partially or together. The system may further include various fluids and fluid management components that provide and store fluids, including, but are not limited to, pumps, valves, flow controls, temperature, degassing controls, irrigation and aspiration capabilities. Various power sources and protectors may also be housed.

[0032] cart The cart 110 may generally be configured in a variety of ways and form factors based on the particular application and procedure. In some cases, the system may include multiple carts configured in similar or different configurations. In some embodiments, the cart may be configured and arranged for use in a radiology environment, and in some cases in coordination with imaging (e.g., CT, cone beam CT, and / or MRI scans). In other embodiments, the cart may be arranged for use in an operating room and sterile environment, or in a robotic operating room, and may be used alone or as part of a robotic surgical procedure, where a surgical robot performs specific tasks before, during, or after the use and delivery of the acoustic cavitation / histotripsy system. To that end, and depending on the procedure environment according to the above-mentioned embodiments, the cart may be positioned to provide sufficient working space and access to various anatomic regions of the patient (e.g., torso, abdomen, flank, head, neck, etc.) while providing working space for other systems (e.g., anesthesia cart, laparoscopic tower, surgical robot, endoscopy tower, etc.).

[0033] The cart may also cooperate with a patient surface (e.g., a table or bed) such that the patient may be positioned and repositioned in multiple positions, angles, and orientations, including allowing pre-operative, intra-operative, and post-operative changes. Additionally, the cart may include the ability to interconnect and communicate with one or more external imaging or image data management and communication systems, including but not limited to one or more modalities of ultrasound, CT, fluoroscopy, cone beam CT, PET, PET / CT, MRI, enhanced fluoroscopy, optical, ultrasound, image fusion, and / or image flow, to support a procedure and / or environment of use, including physical / mechanical interoperability (e.g., compatible within a cone beam CT workspace for collecting imaging data before, during, and / or after tissue disruption).

[0034] In some embodiments, one or more carts can be configured to work together. As an example, one cart may include a bedside mobile cart equipped with one or more robotic arms available with treatment transducers and treatment generators / amplifiers, etc., while a companion cart working cooperatively at a distance from the patient may include a surgical robot and integrated imaging and console / display for controlling the robot and treatment facets similar to a master / slave configuration.

[0035] In some embodiments, the system may include multiple carts all subordinate to one master cart equipped to perform acoustic cavitation procedures. In some arrangements and cases, one cart configuration may allow for storage of certain subsystems at a distance to reduce operating room clutter, while another coordinated cart may include essentially bedside subsystems and components (e.g., delivery systems and procedures).

[0036] Numerous permutations and configurations of cart designs are possible, and these examples do not limit the scope of the disclosure in any way.

[0037] Tissue disruption Histotripsy involves short, high amplitude focused ultrasound pulses that generate dense, energetic "bubble clouds" capable of targeted tissue fractionation and destruction. Histotripsy is capable of well-defined tissue fractionation and destruction at the subcellular level when bulk tissue is targeted, as well as the formation of controlled tissue erosions when directed at tissue interfaces, including tissue / fluid interfaces. Unlike other forms of ablation, including thermal and radiation-based methods, cytotripsy does not rely on thermal or ionizing (high) energy to treat tissue. Instead, cytotripsy uses acoustic cavitation, which is generated at a focal point and mechanically affects tissue structures, in some cases liquefying, suspending, solubilizing, and / or disrupting tissue into intracellular components.

[0038] Histotripsy can be applied in various forms, including: 1) Intrinsic threshold histotripsy: A pulse is delivered with 1-2 cycles of high amplitude reverse / extensional phase pressure above the intrinsic threshold (e.g., up to 24-28 MPa for aqueous soft tissues) to generate cavitation in the medium. 2) Impact scattering histotripsy: A pulse is delivered with a duration of typically 3-20 cycles. The shock wave (normal / compression phase) scattering from the first individual microbubbles generated forms a reverse shock wave that constructively interferes with the incoming reverse / extensional phase to form a high amplitude reverse / rarefaction phase above the intrinsic threshold. Thus, a collection of cavitation microbubbles is generated. The amplitude of the extensional phase of the pulse is sufficient for bubble nuclei in the medium to undergo inertial cavitation at the focal zone for the duration of the pulse. These nuclei invert and scatter the incident shock wave that constructively interferes with the incident wave above the threshold for intrinsic nucleation. 3) Boiling histotripsy: A pulse with a duration of approximately 1-20 ms is employed. Absorption of the shock pulse rapidly heats the medium, lowering its intrinsic nucleation threshold, and when this threshold coincides with the peak negative pressure of the incident wave, a boiling bubble forms at the focal point.

[0039] The high pressures generated at the focal point create a cloud of acoustic cavitation bubbles above a certain threshold level, which causes localized stresses and strains in the tissue and mechanical destruction without significant heat deposition. At pressure levels where cavitation does not occur, minimal effects are observed in the tissue at the focal point. This cavitation effect is only observed at pressure levels significantly greater than those that define the inertial cavitation threshold in water over similar pulse durations, at peak negative pressures of the order of 10-30 MPa.

[0040] Histotripsy can be performed in many 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 transmitting acoustic pulses transcutaneously through the overlying (intervening) tissue to the focal zone (treatment zone and location). Assuming that the bubbles generated by histotripsy are visible, for example, as highly dynamic echogenic areas in B-mode ultrasound images, allowing continuous visualization throughout the use (and associated procedure), further targeting, planning, guidance, and monitoring can be achieved by direct visualization via ultrasound imaging. Similarly, treated and fractionated tissues exhibit dynamic changes (typically decreases) in echogenicity that can be used to assess, plan, observe, and monitor the treatment.

[0041] Typically, in histotripsy, an ultrasound pulse with one or more acoustic cycles is applied, and bubble swarm formation relies on the pressure-relief scattering of a positive shock front (sometimes exceeding 100 MPa, P+) from an initial sparsely distributed bubble (or even a single bubble), which is called the "shock scattering mechanism."

[0042] This mechanism relies on a single (or a few sparsely distributed) bubble being initiated at the first negative half cycle of the pulse at the focal point of the transducer. A microbubble cloud is then formed due to the pressure release backscattering of the positive high peak shock front from these sparsely initiated bubbles. These backscattered high amplitude compressional waves exceed the intrinsic threshold, thus forming a local dense bubble cloud. Each subsequent acoustic cycle then induces further cavitation by backscattering from the bubble cloud surface, which grows towards the transducer. As a result, elongated dense bubble clouds growing on the acoustic axis opposite to the ultrasonic propagation direction are observed in the shock scattering mechanism. This shock scattering process generates bubble clouds depending not only on the negative peak pressure, but also on the number of acoustic cycles and the amplitude of the positive shock. Without the inclusion of at least one dense shock front evolving due to nonlinear propagation, dense bubble clouds do not occur when the negative peak half cycle is below the intrinsic threshold.

[0043] When fewer than two cycles of ultrasonic pulses are applied, shock scattering is minimized and the generation of a dense bubble cloud depends on the negative half-cycle of the applied ultrasonic pulse exceeding the "intrinsic threshold" of the medium. This is called the "intrinsic threshold mechanism."

[0044] This threshold may be in the range of 26-30 MPa for soft tissues with high water content, such as those in the human body. In some embodiments, using this inherent threshold mechanism, the spatial extent of the wound is well-defined and relatively predictable. At negative peak pressures (P-) not much higher than this threshold, reproducible sub-wavelength wounds as small as half the -6 dB beamwidth of the transducer can be produced.

[0045] High frequency histotripsy pulses result in smaller minimum reproducible wound sizes, which is beneficial in applications requiring precise wound creation. However, high frequency pulses are susceptible to attenuation and aberrations, making treatments with high penetration depths (e.g., ablation depths in the body) or in highly aberrated media (e.g., transcranial procedures or procedures in which the pulse is delivered within bone) problematic. Histotripsy may also be applied as low frequency "pump" pulses (typically having frequencies between 100 kHz and 1 MHz with <2 cycles) with high frequency "probe" pulses (typically having frequencies in the range of 2 MHz and 10 MHz with <2 cycles, greater than 2 MHz), where the peak negative pressures of the low and high frequency pulses interfere constructively to exceed the intrinsic threshold of the target tissue or media. Low frequency pulses, which are highly resistant to attenuation and aberrations, raise the peak negative pressure P-level for a region of interest (ROI), whereas high frequency pulses, which provide high precision, pinpoint the target site within the ROI and raise the peak negative pressure P- above the intrinsic threshold. This approach may be referred to as "dual frequency," "dual beam histolysis," or "parametric histolysis."

[0046] Additional systems, methods, and parameters for achieving optimized tissue disruption using various parameters enabling impact scattering, characteristic thresholds, and various frequency compounds and bubble manipulation are included herein as part of the systems and methods disclosed herein, including additional means for controlling tissue disruption concomitant with steering and positioning of the focal spot, and simultaneously managing tissue effects (e.g., pre-focal collateral thermal damage) within the treatment site or intervening tissue. Additionally, various systems and methods are disclosed that may include multiple parameters such as, but are not limited to, frequency, operating frequency, center frequency, pulse repetition frequency, pulses, bursts, number of pulses, cycles, pulse length, pulse amplitude, pulse period, delay, burst repetition frequency, sets of former, multiple sets of loops, multiple and / or different sets of loops, loop sets, various combinations or arrangements, and the like, are included as part of the present disclosure, including future envisioned embodiments.

[0047] Treatment components The treatment subsystem may function with other subsystems to create, optimize, achieve, visualize, monitor, and control acoustic cavitation, also referred to herein below as "histotripsy," including boiling histotripsy and other thermal high frequency ultrasound approaches. Note that the disclosed invention may also be advantageous for other acoustic treatments that do not involve cavitation, mechanical, or histotripsy components. The treatment subsystem may include an ultrasonic treatment transducer and a pulse generator system configured to deliver ultrasonic pulses to tissue, among other features.

[0048] To create and achieve histotripsy and derivatives of histotripsy, the treatment subsystem may also include components including, but not limited to, one or more function generators, amplifiers, treatment transducers, and power sources.

[0049] The treatment transducer may comprise a single element or multiple elements configured to be excited with high amplitude electrical pulses (>1000V or other voltages that may be harmful to living organisms). The amplitude required to drive a treatment transducer for tissue disruption varies depending on the transducer design, the material used (e.g., solid or polymer / piezoelectric composites, including ceramic or single crystal), and the transducer center frequency, which is directly proportional to the thickness of the piezoelectric material. Therefore, a transducer operating at a high frequency requires a lower voltage to generate a given surface pressure than that required for a low frequency treatment transducer. In some embodiments, the transducer elements are formed using piezoelectric polymer composites or solid piezoelectric materials. Furthermore, the piezoelectric material may be of polycrystalline / ceramic or single crystal form. In some embodiments, the transducer elements may be formed using silicon using MEMs technology, including CMUT and PMUT designs.

[0050] In some embodiments, the function generator may include a field programmable gate array (FPGA) or other suitable function generator, where the FPGA is configured with parameters previously disclosed herein including but not limited to frequency, pulse repetition frequency, burst, burst number, burst including pulse, pulse length, pulse period, delay, burst repetition frequency, or period, burst set including parameter set, loop set including various parameter sets with or without delay or with variable delay, multiple loop sets may be repeated, and / or new loop sets may be introduced with variable and independently controlled time delays and with various combinations and permutations throughout.

[0051] In some embodiments, the generator or amplifier may be a general purpose single cycle or multi-cycle pulse generator and may be configured to support all anticipated clinical applications and use environments discussed later in this disclosure with Class D via drive or inductive drive. In other embodiments, the Class D or inductive current driver may be configured to include a transformer and / or autotransformer drive circuit that further provides step up / down components and in some cases preferably allows for amplitude step up. These may include certain protection features that further support the system and provide capabilities to protect other components of the system (e.g., treatment transducer and / or amplifier circuit components) and / or the user from various hazards including but not limited to electrical safety hazards that may potentially cause harm, damage or problems to the use environment, the system and the treatment system and the user.

[0052] The disclosed generators may provide and support the ability to set and read treatment start / stop, voltage levels, pulse and / or burst repetition frequencies, cycle counts, duty cycles, active channels and delays, etc., along with the system's ability to select, modify and control (through available software tools) a variety of parameters including, but not limited to, those already disclosed, and to modulate pulse amplitude on fast time scales independent of high voltage supplies and / or other service, diagnostic or therapeutic characteristics.

[0053] In some embodiments, the procedure subsystems and / or components thereof, such as amplifiers, further include integrated computing capabilities, may be networked, connected, accessed, and / or may be removable / portable, modular, and / or interchangeable between systems, and / or may be driven / commanded from / by other systems or in various combinations. Other systems may include other acoustic cavitation / histotripsy, HIFU, HITU, radiation therapy, radiofrequency, microwave, cryoablation systems, guidance and localization systems, surgical towers with laparoscopes, single incision / single port, endoscopic and non-invasive surgical robots, laparoscopes, or other energy-based or vision systems, surgical system racks or booms, imaging carts, and the like.

[0054] In some embodiments, the one or more amplifiers may include a class D amplifier and associated drive circuitry including matching network components. Depending on the electrical impedance of the transducer element and the selection of matching network components (e.g., an LC circuit consisting of a series inductor L1 and a parallel capacitor C1), the combined impedance may be set aggressively low to have the high amplitude electrical waveform required to drive the transducer element. The maximum amplitude of the class D amplifier, depending on the circuit components used, including the driving MOSFET / IGBT transistors, matching network components or inductors and transformers or autotransformers, may typically be in the low kV (e.g., 1-3 kV) range.

[0055] The treatment transducer elements are excited with an electrical waveform having an amplitude (voltage) that produces a pressure output sufficient for the tissue ablation treatment. The excitation electric field can be defined as the waveform voltage required for the thickness of the piezoelectric element. For example, a piezoelectric element operating in a 1 MHz transducer is half the thickness of an equivalent 500 kHz element and will therefore require half the voltage to achieve the same electric field and surface pressure.

[0056] Integrated Imaging The disclosed system may include various imaging modalities for the user to visualize, monitor, and collect / use feedback of the patient's anatomy, surrounding and intervening tissues along with associated regions of interest and treatment / treatment sites to evaluate, plan, perform treatment, and adjust treatment parameters as needed. The imaging modalities may include various ultrasound, X-ray, CT, MRI, PET, fluoroscopy, optical, contrast or drug enhanced versions, and / or various combinations thereof. It is further disclosed that various image processing and characterization techniques may also be utilized to provide enhanced visualization and user decision making. These may be selected or commanded manually by the user or automatically by the system. The system may be configured to enable parallel switching, overlay, 3D reconstruction, segmentation, registration, multi-modal image fusion, image flow, and / or any method of providing the user with identification, definition, and notification of various aspects of using imaging during treatment as displayed on various system user interfaces and displays. Examples may include, by way of non-limiting example, defining, displaying, characterizing potential treatment sites in, on, and / or around a region of interest, organ system, organ or tissue, and identifying critical structures such as ducts, blood vessels, nerves, ureters, fissures, capsules, tumors, tissue trauma / injury / disease, other organs, connecting tissues, etc., and / or the interactive context of one or more of them (e.g., tumor-draining lymph or blood vessels, or a tumor adjacent to an organ capsule or under another organ).

[0057] The system may be configured to include built-in integrated imaging hardware, software, sensors, probes, wetware, and / or may be configured to communicate and interconnect with external imaging and image processing systems. The above-mentioned components may also be integrated into the treatment subsystem components of the system, where the probe, imaging array, etc. may be electrically, mechanically, or electromechanically integrated with the treatment transducer. This may provide the ability to have geometrically aligned imaging and treatment in some cases, where the treatment is in direct field of view and in some cases coincident with the imaging. In some embodiments, this integration may include a fixed orientation of the imaging capability (e.g., imaging probe) in the context of the treatment transducer. In other embodiments, the imaging solution may be moved or adjusted in its position, including modifying the angle, range (e.g., distance from the treatment transducer or patient), rotation (e.g., imaging plane in the example of an ultrasound probe), and / or other parameters, including dynamic movement / adjustment during active imaging. The imaging component or probe may be oriented and positioned relative to the treatment transducer and / or another aspect of the system, such as a robotic positioning component. decision The information may be encoded so that it can be read.

[0058] In one embodiment, the system may include built-in ultrasound further configured to allow the user to visualize, monitor and receive feedback on the treatment site through the system display and software, including ultrasound imaging and characterization (in various forms) and ultrasound-guided planning and ultrasound-guided treatment, all in real time. The system may be configured to allow the user to image the patient manually, semi-automated, or fully automated means (e.g., by hand or using a robotic imager).

[0059] In some embodiments, imaging feedback and monitoring may include monitoring changes in backscatter from bubble populations, speckle reduction in backscatter, backscatter speckle statistics, tissue mechanical properties (i.e., elastography), tissue perfusion (i.e., ultrasound contrast), shear wave propagation, acoustic emission, electrical impedance tomography, and / or various combinations thereof, including display or integration with other forms of imaging (e.g., CT or MRI).

[0060] In some embodiments, imaging, including feedback and monitoring of backscatter from the bubble cloud, can provide immediate indication as to whether the tissue disruption process has been initiated or is being properly maintained, or has ceased. decision For example, this method allows for continuous monitoring of real-time drug delivery, tissue erosion, etc. This method can also provide feedback that allows the tissue disruption process to be initiated at a high intensity and maintained at a much lower intensity. For example, the backscatter feedback can be monitored by any transducer or ultrasound imager. By measuring the feedback on the treatment transducer, an associated transducer can transmit interrogation pulses or be configured to passively detect cavitation. Also, the nature of the feedback received can be used to adjust acoustic parameters (and related system parameters) to optimize the drug delivery and / or tissue erosion process.

[0061] In some embodiments, imaging and speckle reduction, including feedback and monitoring from backscatter, may be configured in the system.

[0062] For systems that include feedback and monitoring via backscatter, and as a background measure, this process results in changes in the size and distribution of acoustic scattering as the tissue is gradually mechanically fragmented, or in other words homogenized, disrupted, or eroded tissue. At some point in the process, the size and density of the scattering particles are reduced to a level where the ultrasound is nearly not scattered, or the amount of scattering is significantly reduced. This results in a significant reduction in speckle, which is a constructive and destructive interference pattern inherent to the bright and dark spots seen in images when an inherent illumination source, in this case ultrasound, is used. After some treatment time, dark areas appear in the treatment mass as a result of the speckle reduction. The amount of speckle reduction is related to the amount of tissue fragmentation, and therefore can be related to the size of the remaining tissue fragments. When this size is reduced to intracellular levels, the cells are presumed to be non-viable. Thus, treatment can proceed until the desired speckle reduction level is reached. Speckle is easily visible and evaluated with standard ultrasound imaging systems. Specialized transducers and systems, including those disclosed herein, can also be used to evaluate backscatter changes.

[0063] Furthermore, in systems involving feedback and monitoring via speckle, and as a means of background, the image remains largely unchanged between frames unless the scattering distribution changes, and no movement is seen in the imaged object. However, long before the scattering is reduced to a size sufficient to cause speckle reduction, it may change enough to be detected by signal processing and other means. This set of techniques may act as a detector of statistical changes in speckle. For example, the size and location of one or more speckles in the image may begin to decorrelate before observable speckle reduction occurs. Speckle decorrelation after appropriate motion compensation may be a sensitive metric for mechanical disruption of tissue, and therefore a metric of treatment effectiveness. The feedback and monitoring techniques allow early observation of changes resulting from the acoustic cavitation / histotripsy process, and may identify tissue changes prior to substantial or complete tissue effects (e.g., erosion occurrence). In one embodiment, this method may be used to monitor the acoustic cavitation / histotripsy process for improved drug delivery, where the treatment site / tissue is temporarily disrupted and tissue damage / erosion is undesirable. In other embodiments, this may involve speckle decorrelation due to scattering shift in the increasingly fluidized treatment mass, for example in cases where partial or complete tissue erosion is desired.

[0064] For systems involving feedback and monitoring via elastography, and as a background measure, as the treatment site / tissue is further subdivided by acoustic cavitation / hisotripsy (homogenization, fracturing, or erosion), its mechanical properties change from a soft but interconnected solid to a viscous fluid or paste with little long-term interaction. These changes in mechanical properties can be measured by various imaging modalities including MRI and ultrasound imaging systems. For example, ultrasound pulses can be used to generate forces (i.e. radiation forces) in a localized tissue mass. Tissue responses (displacements, strains, velocities) change significantly during histotripsy treatment to allow visualization of the histotripsy state by imaging or other quantitative means. decision This becomes possible.

[0065] The system may also include feedback and monitoring via changes in shear wave propagation. As a background measure, tissue subdivision makes the tissue fluid and non-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 disruption process. For example, ultrasound and MRI imaging systems may be used to observe the propagation of shear waves. The attenuation of such waves in the mass after treatment is used as a metric of tissue destruction or disruption. In one system embodiment, the system and auxiliary subsystems may be used to generate and measure interacting shear waves. For example, two adjacent ultrasound foci perturb the tissue by pressing in a certain way. If the adjacent foci are in a fluid, the shear waves will not propagate and interact. If the tissue does not fluidize, the interaction is detected by external means, for example, by a difference frequency that is only detected when two shear waves interact nonlinearly, and its disappearance correlates with tissue damage. Therefore, systems can be configured to use this approach to improve feedback and monitoring of acoustic cavitation / histotripsy procedures.

[0066] For systems involving feedback and monitoring via acoustic emissions, and as a background measure, as a tissue mass is fragmented, its effect on acoustic cavitation / tissue disruption (e.g., here, bubbles) changes. For example, bubbles become larger and have different lifetimes and collapse characteristics for intact tissue and fluidized tissue. Even after tissue is fragmented to generate larger bubbles or cooperative interactions between bubbles, bubbles continue to move and interact, all of which results in changes in acoustic emissions. These emissions are audible and change during treatment. Analysis of these changes and their correlation to treatment effectiveness allows monitoring of treatment progress and can be configured as a feature of the system.

[0067] For systems that include feedback and monitoring via electrical impedance tomography, and as a background measure, an impedance map of the treatment site can be created based on the spatial electrical properties of the entire treatment site. Imaging of the electrical conductivity and permittivity of the treatment site on the patient can be inferred from skin surface electrical measurements. Conductive electrodes are attached to the patient's skin and a small alternating current is applied to some or all of the electrodes. One or more known currents are injected into the surface and the voltage is measured at several points using the electrodes. The 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 employed. Measurements of the electrical properties of the treatment site within the skin surface can be obtained from the impedance map, and changes in the acoustic cavitation / tissue disruption (e.g., specifically the bubble population) and its location and the tissue disruption process can be monitored using the system and auxiliary subsystems configured.

[0068] The user, through the system software, user interface and display, can further select, annotate, mark, highlight and / or outline various regions of interest or treatment locations and defined treatment targets (on the images) that can be used to command and direct the system where to image, examine and / or treat. In some arrangements, the user may use a manual ultrasound probe (e.g., a diagnostic handheld probe) to perform the procedure. In other arrangements, the system uses a robotic and / or electromechanical positioning system to perform the procedure that is directed and / or automated by the system or vice versa, allowing for a combination of manual and automated use.

[0069] The system may further include the ability to perform image recording, including imaging and image data set recording, which allows the system to be guided and located on the patient, including the treatment site (e.g., tumor, critical structures, bone structures, body structures, and specific features, etc.). In one embodiment, the system allows the user to use integrated ultrasound to image and identify an area of ​​interest, such as the liver, and through the system software, select and mark / display a tumor (or its surrogate marker) contained within the liver, which the system records in a coordinate system defined by the system, thus further enabling the therapy and robotic subsystem of the system to deliver synchronized acoustic cavitation / histotripsy to the marked tumor. The system includes the ability to record various image sets together, including those already disclosed, and provide guidance and location (e.g., of the treatment transducer to a CT or MRI / ultrasound fusion image with image tracking by the treatment transducer and robotic subsystem).

[0070] The system also includes the ability to function alone or in a variety of interventional, endoscopic, surgical environments including other systems (surgical / laparoscopic towers, vision systems, endoscopy systems and towers, ultrasound-based endoscopic ultrasound (flexible and rigid), percutaneous / endoscopic / laparoscopic, and minimally invasive guidance systems (e.g., optical, electromagnetic, shape sensing, ultrasound-based, etc.), which may also function with or include various optical imaging capabilities (e.g., fiber and / or digital). The disclosed system functions with these systems, or in some embodiments cooperates with them, or in other embodiments all or some of the system may be integrated into the above systems / platforms (e.g., acoustic cavitation / histotripsy-based endoscopic systems or laparoscopic surgical robots). In many of these environments, the surgical transducers are used, for example, before, during, or after the use of an optically guided endoscope / bronchoscope. , or in another example, at the point where a laparoscopic robot (e.g., an intuitive Da Vinci* Xi system) is viewing / manipulating the tissue / treatment site. Additionally, these embodiments and examples may include cases where other systems / platforms are used to (locally) deliver fluid to allow for the creation of an artificial acoustic window that would not normally exist (e.g., fluidization of lung segments or lobes in preparation for acoustic cavitation / histotripsy via non-invasive transthoracic therapy (e.g., transducers placed externally on / around the patient)). The systems disclosed herein may also include all or some of the subsystem hardware packaged within other system carts / consoles / systems described herein (e.g., acoustic cavitation / histotripsy systems and / or subsystems integrated with or operated from this navigation or laparoscopic system).

[0071] The system is also configured to display real-time visualization of the bubbles in a spatiotemporal manner, including tissue effects during / after treatment resulting from tissue / bubble interactions, through the various parameters mentioned above and others, and the system can dynamically image, visualize and display the bubbles and their changes (decrease and increase in echogenicity) which may include intensity, shape, size, location, morphology, persistence, etc. These features allow the user to continuously track and follow the treatment in real time in one integrated procedure and interface / system, and to ascertain in situ treatment safety and effectiveness (vs. other interventional or surgical modalities) where multiple procedures are required to achieve, where the treatment effect is not visible in real time (e.g. radiation procedures) or is not possible to achieve (e.g. real-time visualization of local tissue during thermal ablation), and / or where other procedures require a more invasive approach (e.g. incision or puncture) and repeated imaging with a scanner between treatment steps (e.g. CT or MRI scans). The above disclosed systems, subsystems, components, methods, features, and workflows / methods of use may be implemented in any manner, including through any available hardware, software, user interfaces, and environments of use, and further improvements, modifications, and inventions in this field, along with the resulting data and the use of this data for analytical, artificial intelligence, or digital health applications and systems, are deemed to be within the scope of this disclosure.

[0072] Robotics The system may include various robotic subsystems and components, including but not limited to one or more robotic arms and a controller, which may further function in conjunction with other subsystems or components of the system to achieve and monitor acoustic cavitation / hisotripsy. As previously discussed herein, the robotic arms and control systems may be integrated into one or more cart configurations.

[0073] For example, one system embodiment includes a cart with an integrated robotic arm and control system, procedure, integrated imaging, and software, where the robotic arm and other subsystems listed are controlled by the user through a single bedside cart form factor.

[0074] In another embodiment, the robotic subsystem is comprised of one or more separate carts that are driven from separate masters or carts in a master / slave configuration, with the robotic cart located near the bed / patient and the master located at a distance from the cart.

[0075] The disclosed robotic arms are comprised of multiple joints, segments, and degrees of freedom, and may also include a variety of integrated sensor types and encoders implemented for various uses and safety features. Sensing techniques and data may include, by way of example, vision, potentiometer, position / location determination, kinematics, force, torque, velocity, acceleration, dynamic loads, and / or others. In some cases, sensors may be used to allow a user to indicate robot commands (e.g., hand gestures that move the robot to a preferred set position or dock home). Additional details regarding the robotic arm may be found in U.S. Patent Application Publication No. 2013 / 0255426 to Kassow et al., which is incorporated herein by reference in its entirety.

[0076] The robotic arm receives control signals and commands from a robotic control system that may be housed on the cart. The system may be configured to provide a variety of functionality including, but not limited to, position, tracking, pattern, actuation, and event / action.

[0077] The positions may be configured to include fixed positions, pallet positions, time controlled positions, distance controlled positions, variable time controlled positions, variable distance controlled positions.

[0078] The tracking may be configured to include time-controlled tracking and / or distance-controlled tracking.

[0079] A pattern of movement can be configured to include a sequence of positions with intermediate positions or waypoints on a prescribed path in space.

[0080] The trigger may be configured with a variety of sensor means, including but not limited to distance time measurement means, time, and / or those disclosed herein, including visual / imaging based force, torque, position determination, energy / power feedback, and / or others.

[0081] The events / actions can be configured to encompass a variety of examples including proximity (toward / away from a target object) based activation or deactivation of various end effectors (e.g., treatment transducers), starting / stopping / pausing an event, activating or switching between event / action triggers, initiating a movement pattern and changing / switching between movement patterns, and / or time-based tasks and spatiotemporal temporal definitions.

[0082] In one embodiment, the system includes a three degree of freedom robotic positioning system that allows the user to micro-position the treatment transducer in an X, Y, Z coordinate system (through the system's software and associated user interface), with gross macro-positioning of the transducer (e.g., aligning the transducer to the patient's body) completed manually. In some embodiments, the robot may include six degrees of freedom, including X, Y, Z, as well as pitch, roll, and yaw. In other embodiments, the robotic subsystem may include additional degrees of freedom to position the robot arm supporting the base on a linear axis extending parallel to the general orientation of the patient surface and / or to adjust the height of the support base up or down to modify the position of the robot arm relative to the patient, patient surface, cart, docking subsystem, additional robots / robotic arms, and / or additional surgical systems, including, but not limited to, a surgical tower, imaging systems, endoscopic / laparoscopic systems, and / or others.

[0083] The one or more robotic arms may also include various features to aid in manual or semi-manual manipulation and correction of the arm position, which may be interconnected at or between the treatment transducer and most distal joints of the robotic arm. In some embodiments, the features are configured to include a handle to allow one-handed or two-handed manipulation and manual control. The handle may also be configured to include user input and electronic control features of the robotic arm to command various drive capabilities or modes and actuate the robot (e.g., activate or deactivate a free drive mode) to assist in coarse or fine positioning of the arm. The workflow for the initial positioning of the robotic arm and treatment head may be configured to first position the treatment transducer / head in the combined solution so that the treatment transducer is directly interconnected with the arm, or in a different workflow, the user may first configure the combined solution and then interconnect the robotic arm to the treatment transducer / combined solution as a later / final configuration step.

[0084] In some embodiments, the robotic arms may include laparoscopic, single port, endoscopic, hybrid or combination thereof, and / or other robotic robotic arms, where the robot of the system is a slave to a master that controls the arms, and potentially other arms equipped to simultaneously perform other tasks (vision, imaging, grasping, cutting, ligating, sealing, closing, stapling, ablation, suturing, marking, etc.) including actuating one or more laparoscopic arms (and instruments) and various tissue disruption system components. For example, a laparoscopic robot may be utilized to prepare the surgical site, including manipulating the organ position for more optimal acoustic access and in some cases further stabilizing the organ to minimize respiratory motion. In conjunction with and in parallel with this, a second robotic arm may be used to achieve non-invasive acoustic cavitation through the body cavity as observed by real-time imaging from a surgical transducer (e.g., ultrasound) with simultaneous visualization via a laparoscopic camera. In other related aspects, similar approaches may be utilized in combination with endoscopic and non-invasive approaches, as well as in combination with endoscopic, laparoscopic and non-invasive approaches.

[0085] join The system includes various coupling subsystem embodiments that can be utilized and configured to enable acoustic coupling to the patient to provide effective acoustic cavitation / histodisruption (e.g., providing an acoustic medium between the transducer and the patient and its support). These can include different form factors, including open and enclosed solutions, and several arrangements that can be configured to enable dynamic control over the acoustic medium (e.g., temperature, dissolved gas content, particle filtration levels, sterility, etc.). Such dynamic control components can be directly integrated into the system (in the cart) or can be external but in communication with the system.

[0086] The bonding subsystem generally includes, at a minimum, a bonding medium, a reservoir / container for storing the bonding medium, and a support structure. In most embodiments, the bonding medium is water, and the water may be conditioned before or after processing (e.g., refrigeration, degassing, filtering, etc.). Various conditioning parameters may be employed based on the configuration of the system and its intended use / application.

[0087] The reservoir or medium container is shaped or shaped to accommodate / fit the patient, allowing the treatment transducer to engage and function within an acoustic medium (the minimum amount of medium that allows the treatment transducer to be placed and / or moved in one or more treatment positions or patterns, and at various distances or depths from the patient, etc.) for a defined required working space, and the reservoir or medium container can mechanically support load and load distribution through the use of mechanical and / or electromechanical support structures. The containers can be of various shapes, sizes, curvatures, dimensions, and made of various materials (single, multiple, composite, etc.) that can be constantly changing. In some embodiments, they can include features such as films, drapes, membranes, bellows, etc. that can be inserted and removed and / or fabricated therein. They can also house various sensors, drainage tubes, lights (e.g., LEDs), markings, text, etc.

[0088] In one embodiment, the reservoir or media container houses a sealable frame in which the membrane and / or film sits, providing a comfortable means of contact with the reservoir (which will later include the treatment transducer) as an interface to the patient, and also providing a barrier to the media (e.g., water) between the patient and the transducer. In another embodiment, the membrane and / or film has an opening, the edges of which provide a mechanical seal to the patient, but in contrast allow media communication with the patient (direct patient-water interface). The reservoir or media container superstructure in both of these examples may further provide a proximal portion (e.g., top) of the structure that is open or enclosed (e.g., to prevent leakage or provide additional features).

[0089] The disclosed membranes can be composed of various elastomers, viscoelastic polymers, thermoplastics, thermoplastic elastomers, thermoset polymers, silicones, urethanes, rigid / flexible copolymers, block copolymers, random block copolymers, etc. The materials can be hydrophilic, hydrophobic, surface modified, coated, extracted, etc., and can also contain various additives that improve performance, appearance, or stability. In some embodiments, the thermoplastic elastomer can be styrene-ethylene-butylene-styrene (SEBS) or other similar strong and flexible elastomers.

[0090] The materials may be formed into useful membranes through molding, casting, jetting, ultrasonic jetting, and / or any other processing method that produces useful embodiments. They may be disposable or disposable / reusable. They may be non-sterile, aseptically cleaned, or aseptic, and sterilization may include any known method, including but not limited to ethylene oxide, gamma, E-beam, autoclave, steam, peroxide, plasma, chemicals, etc. The membrane may further comprise an outer molded frame that provides mechanical stability during assembly of the coupling subsystem. Various parameters of the membrane, including thickness, thickness profile, density, morphology (e.g., polymer molecular weight and copolymer ratio), are optimized for this method of use, including explicit optimization to maximize acoustic properties, and minimize impact on cavitation initiation threshold and / or ultrasound imaging artifacts, including but not limited to membrane reflections.

[0091] The open reservoir or media container may include various methods of filling with water, in some cases to prescribed specifications (such as temperature and gas saturation levels), including the use of media or water that is pre-prepared and delivered to it, or may include additional features integrated into the design (e.g., ports, valves, hoses, tubing, fittings, bags, pumps, etc.) that allow for filling and draining.

[0092] The enclosed reservoir or media container may include various features for sealing, in some embodiments to the proximal / upper portion or structure of the reservoir / container, or in other cases to the transducer or features on the transducer housing. Additionally, some embodiments may include dynamic capabilities to control the volume of fluid within these designs to minimize the potential for bubbles or turbulence within the fluid. To that end, integrated features may be provided that allow for fluid flow and control thereof (ability to supply / remove fluid on demand), including some of the capabilities to monitor and control various fluid parameters disclosed above. To provide this functionality, the overall system, and associated subsystems as part of it, may include a fluid regulation system that may house various electromechanical devices, systems, power, sensing, computation, and control systems, etc.

[0093] The combined support system may include a variety of mechanical support devices that interconnect the reservoir / container and media to the patient and the workspace (e.g., bed). In some embodiments, the support system may include a mechanical arm with three or more degrees of freedom. The arm may be interconnected to one or more portions of the reservoir or container along with one or more portions (and features) of the bed, including, but not limited to, a frame, rails, customized rails, or inserts. The arm may be a feature that is mounted to one or more carts, which may be configured in a variety of non-limiting arrangements, and in some cases, the cart may only serve to support and provide the disclosed support structure.

[0094] In some embodiments, the support structure and arm is a robotic arm implemented as a stand-alone cart or integrated into a cart having two or more further systems and subsystems, the robotic arm being an arm of another robot for interventional surgery or other type, and may further include various user input features (e.g., positioning into / within the bonding medium) and / or bonding solution features (e.g., filling, draining, etc.) to actuate / control the robotic arm.

[0095] software The system may include a variety of software applications, features, and components that enable a user to interact with, control, and use the system for a number of clinical applications. The software may communicate with and function with one or more of the subsystems, including, but not limited to, procedure, integrated imaging, robotics, and other components, accessories, and equipment of the system.

[0096] Overall, and in no particular order of importance, the software performs the following functions: Initialization and configuration of the system; Servicing the system; Communication and introduction / derivation / storage of data; Allowing the user to modify / operate / configure / control / command various settings and parameters; Eliminating safety and user related risks; Planning treatments; Providing support for various configurations of transducers, robotic arms, and drive systems; Function generator and amplifier circuits / slaves; Examination and treatment ultrasound sequences; Transducer steering and positioning (e.g., electromechanical and electronic beam steering); Treatment patterns; Imaging and imaging probe support; Manual and electromechanical / robotic movements; Treatment and imaging of various dimensions at or around the treatment site (e.g., from one body structure to another); pre-treatment assessment and protocols for measuring / characterizing on-site treatment locations and conditions (e.g., acoustic cavitation / tissue disruption thresholds and heterogeneity); targeting and target alignment; calibration; marking / annotation; location / guidance; documentation; guidance; workflow; providing and guiding procedure steps; autonomous, autonomous execution of treatment plans and protocols during direct monitoring and visualization with real-time imaging displayed through the software including various views and viewports for viewing, communication tools (video, audio, shared, etc.); troubleshooting; providing instructions, warnings, alerts; and / or communication capabilities through various networking devices and protocols. It is further contemplated that the software user interface and supporting displays may include various buttons, commands, icons, graphics, text, etc. for a user to interact with the system in a user-friendly and effective manner, which may be presented in an unlimited number of arrangements, layouts, and designs, and may be displayed in similar or different manners or feature sets for a system that may have one or more displays (e.g., a touch screen monitor and touch pad) and / or be networked to one or more external displays or systems (e.g., another robot, a guidance system, a system tower, a console, a monitor, a touch display, a mobile device, a tablet, etc.).

[0097] Software as part of a representative system including one or more computer processors may support the various function generators (e.g., FPGAs), amplifiers, power supplies, and treatment transducers described above. The software may also allow the user to select the various parameters and settings of the acoustic cavitation / hisotripsy. decision , monitoring and allowing the user to stop / start / modify its parameters and settings upon observing / receiving performance and condition feedback.

[0098] The software may be configured to allow the user to select from a list or menu of multiple transducers and support automatic detection of the transducer upon connection to the system (verification and parameter setting of the appropriate sequence based on the selected application). In other embodiments, the software may update targeting and amplifier settings (e.g., channel) based on the specific transducer selection. The software may also provide transducer recommendations based on pre-treatment and planning inputs. Conversely, if the treatment transducer, amplifier, and / or function generator selection or parameters are incorrect resulting in an error or malfunction, the software may provide an error message or warning to the user. This may further include reporting the details and location.

[0099] In addition to the above, the software may be configured to allow a user to select treatment sequences and protocols from lists or menus and to store selected and / or previously selected sequences and protocols in association with a particular clinical use or patient profile. The associated profile contains relevant patient, procedure, clinical and / or engineering data and may be used to inform, modify and / or guide current or future treatments or procedures / interventions, whether as decision support for the treatment itself or as an active part (e.g., the use of serial data sets to construct and guide new treatments).

[0100] As part of the planning or during treatment, the software (and working in conjunction with other components of the system) allows the user to evaluate and test the acoustic cavitation / tissue disruption thresholds of various locations in a user-selected region of interest or a defined treatment area / mass, and determine the minimum cavitation threshold in this region or area / mass. decision The system can then be adapted to ensure that treatment parameters are optimized to achieve, maintain and dynamically control acoustic cavitation / tissue disruption. In one embodiment, the system allows the user to manually assess and test threshold parameters at various points, including defined boundary points within the borders and central sites / locations of the selected region of interest and treatment area / mass, and the resulting threshold measurements can be reported / displayed to the user and used to update treatment parameters prior to treatment. In another embodiment, the system is configured to allow automated threshold measurements and updates utilizing the robotic subsystems described above, where the user can instruct the robot or the robot can be commanded to perform the measurements autonomously.

[0101] The software may also be configured to work in conjunction with a computer processor and one or more function generators, amplifiers, and treatment transducers to deliver and position optimal acoustic cavitation / histotripsy at and through a selected area / mass in a variety of arrangements, including, but not limited to, systems configured with fixed / natural focal spot placement using a purely electromechanical positioning arrangement, electronic beam steering (with or without electromechanical positioning), electronic beam steering to a newly selected fixed focal spot with further electromechanical positioning, axial (Z-axis) electronic beam steering with lateral (X and Y) electromechanical positioning, fast axial electronic beam steering with lateral electromechanical positioning, fast beam steering in 3D space, dynamically varying one or more acoustic cavitation / histotripsy parameters (e.g., dynamically adjusting amplitude at a treatment area / mass) based on the above capabilities to update treatment parameters based on threshold measurements.

[0102] Other components, accessories and equipment The systems may include computers, computer processors, power supplies including high voltage power supplies, controllers, cables, connectors, networking equipment, software applications for security, communications, integration into information systems including hospital information systems, cellular communication devices and modems, handheld wired or wireless controllers, goggles or glasses for advanced visualization, augmented or virtual reality applications, cameras, sensors, tablets, smart devices, phones, capabilities to utilize the Internet of Things, special purpose "apps" or user training materials and applications (software or paper based), virtual protocols or training devices and / or other useful features, devices, systems, or applications, and / or various other components, accessories, equipment, including, but not limited to, the uses described above.

[0103] System Variations and Methods / Applications In addition to performing a wide range of procedures, the system may enable additional benefits such as improved planning, imaging, guidance, etc. to assist the user. In one embodiment, the system allows the user to create patient, target, and application specific treatment plans, where the system is configured to optimize treatment parameters based on feedback to the system during planning, and where planning may further include the ability to run various examination protocols to gather specific inputs to the system and the plan.

[0104] The feedback may include various energy, power, site, position, tissue, and / or other parameters.

[0105] The system and the above feedback can also be configured and used autonomously (and robotically) to achieve optimal treatment plans and protocols as visualized by real-time imaging during the procedure, allowing the user to directly observe localized treatment tissue effects as the treatment progresses and optionally start / stop / modify treatment. Both testing and treatment protocols can be updated during the course of the procedure at the direction of the user or, in some embodiments, based on logic embedded in the system.

[0106] It is also recognized that many of these advantages further enhance other forms of acoustic treatments, including high intensity focused ultrasound (HIFU), thermal ablation with high intensity therapeutic ultrasound (HITU), including boiling tissue disruption (thermal cavitation), and are considered part of this disclosure.

[0107] In another aspect, the treatment subsystem, including in part one or more amplifiers, transducers, and power sources, can be configured to enable a number of acoustic cavitation and tissue disruption drive capabilities that provide 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 treatment parameters, thereby delivering more energy including more desirable thermal profiles, higher treatment rates and shorter procedure times, enabling electronic beam steering and / or other features.

[0108] The present disclosure also includes novel systems and concepts relating to systems and subsystems that include a novel "universal" amplifier that allows for multiple drive approaches (e.g., single and multi-cycle pulsing), which in some embodiments may include a variety of novel features that further protect the system and user from electrical safety or other hazards (e.g., damage to the transducer and / or amplifier circuitry).

[0109] In another aspect, the system and treatment subsystem includes multiple treatment transducers, which may be configured for specific applications and uses to accommodate treatment across a wide range of operating parameters (target size, depth, location, etc.) and encompass a wide range of operating specifications (discussed in more detail below). The transducers may further be adapted, interconnected, or connected to a coupling subsystem along with a robotic system to position the transducers within or with an acoustic coupling device, which in many embodiments allows for simultaneous imaging and histotripsy treatment through an acceptable acoustic window. The treatment transducers may be used to indicate and / or determine the transducer position within the treatment site. decisionIt may also have an integrated imaging probe or positioning sensor that can provide a direct view (or representation of) the treatment site, and may cause acoustic cavitation / tissue disruption tissue effects and bubble clouds to change appearance and intensity throughout the treatment and depending on the location within the treatment (e.g., tumor, healthy surrounding tissue, critical structures, adipose tissue, etc.).

[0110] The systems, methods, and uses of the systems disclosed herein may be beneficial in filling significant unmet needs in the fields of soft tissue ablation, oncology, immuno-oncology, advanced image-guided procedures, surgical procedures including, but not limited to, open, laparoscopic, single incision, natural orifice, endoscopic, non-invasive, and various combinations thereof, various interventional spaces for catheter-based procedures in vascular, cardiovascular, and / or neurological spaces, cosmetics / aesthetics, metabolism (e.g., type 2 diabetes), plastic materials and reconstruction, ophthalmology and ophthalmology, gynecology and andrology, and other systems, devices, and methods for treating diseased, injured, unwanted, or healthy tissue, organs, or cells.

[0111] Systems and methods are also provided for improving treatment patterns within tissue that may shorten treatment times, increase efficacy, reduce the amount of energy delivered to the patient and pre-focal tissue heating.

[0112] Usage environment The disclosed systems, methods of use, and use of the systems may be performed in a number of environments and settings with or without various support systems such as anesthesia, including but not limited to, procedure suites, operating rooms, hybrid operating rooms, in and out of patient settings, emergency settings, imaging centers, radiology, radiological procedures, oncology, surgery, and / or medical centers, as well as clinics, mobile health care centers or systems, automobiles and related vehicles (e.g., vans), and / or any structure capable of providing temporary procedure support (e.g., tents). In some cases, the systems and / or subsystems disclosed herein may be provided as integrated features into other environments, such as direct integration of tissue disruption. The procedure subsystem, where at a minimum the procedure generator and transducer are integrated, and where the tissue disruption configuration further includes a robotic positioning system or bed-centric design that may be integrated into the scanner in other cases, is integrated into the MRI scanner or patient surface / bed.

[0113] Coordination between imaging and robotic subsystems To effectively treat tissue with histotripsy ultrasound procedures, the ultrasound focus of the procedure system must be precisely positioned on the target tissue (e.g., tumors and blood clots) within the body. For non-invasive procedures such as histotripsy, precise targeting can be guided by real-time imaging such as ultrasound or MRI. The advantages of using ultrasound imaging are that ultrasound is widely available at low cost and can clearly visualize cavitation due to histotripsy. However, ultrasound imaging has many limitations in histotripsy procedures, including: 1) many clinical targets, such as tumors, are not clearly visible with ultrasound; 2) native ultrasound imaging is generally 2D and does not provide accurate 3D mass information for tissue; and 3) targets within the brain cannot be imaged due to the skull and limitations of the acoustic window required for imaging.

[0114] Histotripsy targeting can also be guided by real-time MRI. Tumors and clots are clearly visible on MRI, which generally provides 3D imaging. However, real-time MRI guidance also has limitations in histotripsy procedures, including: 1) high cost of MRI scan time, 2) specialized histotripsy equipment that is MRI compatible and directly integrated is required, and 3) MRI scanner availability is limited.

[0115] This disclosure describes a novel approach for histotripsy targeting without the need for real-time imaging. Described herein are systems and methods that achieve accurate targeting based on imaging scans (e.g., MRI or CT) taken before or during treatment. The approaches described herein may include the combination of surgical guidance capabilities and / or systems, stereotactic setting, and / or inserted fiducial markers with histotripsy.

[0116] Methods and systems for histotripsy targeting based on pre-imaging scans can leverage the capabilities of MRI / CT for 3D imaging and clear visualization of tumor / blood clot contrast. These techniques use software and hardware components that interact and communicate / interconnect with or as part of the histotripsy system, but do not require specialized histotripsy systems, which require physical and electromechanical integration of the MRI / CT. In some embodiments, when only pre-treatment imaging scans are used, these techniques do not require real-time MRI / CT during treatment, thus significantly reducing procedure costs while maintaining high targeting accuracy. In some embodiments, the histotripsy system can communicate and interact with the MRI / CT during surgery and function solely in coordination with them (not integrated as part of the scanner itself).

[0117] The histotripsy targeting systems and methods described herein generally require a set of specific hardware and software systems that may be configured in a variety of ways, including but not limited to a histotripsy transducer, a robotic positioning system coupled to the histotripsy transducer and configured to control and move the position and orientation of the histotripsy transducer during the procedure, a surgical guidance system or subsystem capable of producing variable resolution (low or high resolution) images of the target tissue mass, and a high resolution pre-imaging scan of the target tissue mass prior to the procedure, such as an imaging scan from an MRI or CT system. For example, the histotripsy transducer and robotic positioning arm described herein (FIG. 1) may be used in these novel targeting systems and methods. While any surgical guidance system may be used, generally the surgical guidance system may also be configured to acquire a low resolution image of the target tissue mass, such as an ultrasound or still camera image. The robot and guidance system / subsystem may also be used to record the robot encoded position data, a low resolution real-time image (e.g., ultrasound or optical camera), and a MRI / CT pre-procedure image to provide real-time guidance to the MRI / CT. In some embodiments, and as previously described herein, the MRI / CT data may be registered using rigid and / or elastic deformable models to best fit the pre-operative imaging data with the real-time data and achieve the most accurate registration possible with minimal MRI / CT body divergence.

[0118] FIG. 2 shows a flowchart 200 depicting steps of several exemplary embodiments for performing histotripsy targeting and surgery using the system components described herein, including the histotripsy transducer, the robotic positioning system, and the surgical guidance system. At step 202 of the flowchart 200, the surgical guidance system can receive or access a prior high-resolution image of a patient, including a target tissue mass on or within the patient. The high-resolution image can include, for example, a 2D or 3D MRI or CT scan, cone-beam CT, enhanced fluoroscopic image, etc., of the patient, including the target tissue mass. These images can be anatomically segmented and reconstructed into various 2D or 3D models, including deformation models that account for divergence or shifts due to binding or other pre- / interventional changes in the anatomy. The target tissue mass can include, for example, diseased or abnormal tissue, such as a tumor or cancerous growth, blood clot, polyp, nodule, organ, etc.

[0119] Next, at step 204, the surgical guidance system can acquire a low-resolution image of the target tissue mass. Typically, the surgical guidance system has its own imaging system, which may include optical imaging, near infrared, confocal, coherence tomography, photography, ultrasound, etc. Thus, for purposes of discussion in this disclosure, "high-resolution images" generally refers to the types of images acquired by advanced medical imaging and diagnostic systems, including MRI and CT. These images may be 2D or 3D images, or may undergo further post-processing, including various segmentations, reconstructions, transformations, etc. Additionally, "low-resolution images" as discussed herein generally refer to the types of images acquired by more ubiquitous, less detailed imaging and diagnostic systems, such as diagnostic ultrasound and still / camera / optical imaging.

[0120] Next, at step 206 of flowchart 200, the surgical guidance system or subsystem may match the low-resolution image generated by the surgical guidance system / subsystem with a previously acquired high-resolution image (e.g., a pre-operative or intra-operative CT or MRI image). Alignment The imaging system may be configured to locate the target tissue mass by comparing the image from the guidance system with the prior CT / MRI image. Alignment The guidance system can then correlate the coordinate systems between the images to pinpoint the exact location of the target tissue mass in 2D or 3D space. In some examples, the low-resolution images generated by the surgical guidance system may include ultrasound images with an ultrasound probe positioned in or with a fixed geometry relative to the histotripsy transducer, or in other embodiments, the low-resolution images may include digital optical images of the patient's skin surface with specific landmarks. Alignment The method involves identifying landmarks or standard regions in both high-resolution and low-resolution images and comparing the landmarks or standard regions (e.g., brain scans) to the Alignment At a high level, this may include correlating the coordinate system of the high resolution image with that of the low resolution image using a (base-tool) coordinate system (certain skull or facial features that correspond to the location of the low resolution image). As the low resolution images may be acquired by the guidance system itself and using the robot, the guidance system uses this correlation of (base-tool) coordinate systems to effectively navigate using the high resolution images, and the robot-encoded position data is recorded in the imaging data set. The recorder workflow presented in the system user interface may include fully automated workflows, partially automated workflows, and fully manual procedure steps. Additionally, assuming that tissue disruption creates a highly visible treatment zone, the treatment itself, as visualized by ultrasound, MRI, and / or CT, may be further used during the procedure to also update / enhance the record as necessary or desired.

[0121] Next, at step 208 of flowchart 200, the surgical guidance system or subsystem can identify the location of the histotripsy transducer focal point. In some instances, the surgical guidance can use the location and orientation of the histotripsy transducer itself in combination with the focal length of the transducer to determine the location of the focal point. decisionA number of techniques can be used to identify the location of the histolysis transducer focal spot, including placing standard markers (e.g., optical, electrical, magnetic) on the transducer and identifying these standard markers with a surgical guidance system. By placing standard markers on the histolysis ultrasound transducer that can be detected by the surgical guidance system, the location of the histolysis transducer can be recognized in the coordinate system of the surgical guidance system. In one example, the standard markers can include a set of markers with a unique configuration for a known tool / device. A unique marker configuration (e.g., five spherical optical markers arranged in a specific pattern, such as the optical tracking markers for the Stealth Station or Brainlab surgical guidance systems) can be attached to the surface of the histolysis transducer that can be detected by the surgical guidance system (e.g., by imaging or sensing the markers). The surgical guidance system can then automatically locate and identify the histolysis focal spot in the surgical guidance system coordinates based on the marker configuration location / orientation and the histolysis transducer focal length. In another embodiment, given the known geometry of the transducer and the predicted focal length, intra-procedural scanning can be used to predict the final bubble cluster location using the robot position encoder data (and pose relative to the image set) to predict the location.

[0122] Next, in step 210 of flowchart 200, the surgical guidance system, or robotic positioning system that controls the position and motion / movement of the histotripsy transducer, can calculate the translation coordinates necessary to set the histotripsy focal point at the target tissue mass. These translation coordinates are then input into the robotic positioning system to move the histotripsy transducer appropriately to harmonize the base / tool ​​coordinate system. In some embodiments, software supervision can monitor the position and orientation to verify that the planned and actual site / location are accurate. In additional embodiments, the movement of the histotripsy focal point can be achieved through a combination of electronic steering of the focal point by the transducer (phased array) and mechanical movement of the transducer by the robotic positioning system.

[0123] In step 212, when the histotripsy transducer is in the proper position (e.g., focal point is set on or in the target tissue mass as verified using the recorded real-time and virtual imaging data), a histotripsy procedure may be applied to the target tissue mass by the histotripsy procedure transducer. Typically, the target tissue is a mass, such as a tumor or a blood clot mass. To treat the target mass, the boundary outline or contour of the target tissue mass may be specified with a high-resolution MRI / CT scan. For example, the surgical guidance system may include input features for the user to define a positive margin (a treatment margin that extends outside or is larger than the target tissue mass, such as for treating a cancerous tumor) or a negative margin (a treatment margin that is within or is smaller than the target tissue mass, such as for treating a blood clot), and the extent of the treatment margin (e.g., 1 cm). For example, if a tumor is the target tissue mass, the treatment margin may cover the entire tumor with a user-predefined margin surrounding the tumor to ensure treatment of all tumor cells. For example, if a blood clot is the target tissue mass, the treatment margin covers most of the clot, but leaves the edges of the clot untreated to prevent damage to surrounding normal tissue as defined by the user. After the treatment margin is defined, a surgical guidance system or robotic arm can calculate and generate treatment parameters to cover the target tissue mass and display the treatment margin superimposed on a prior MRI / CT scan of the patient. Fine-tuning or further adjustments to the treatment margin or coordinates can be made if desired by the user. The treatment margin site coordinates are then sent to the robotic control system to move the tissue disruption transducer appropriately, including according to the desired path, pattern, direction, and sequence, and to prevent impact on non-target tissue. decision The parameters may include controlled cooling and / or off-time to achieve therapy. These parameters may further be displayed through one or more user interfaces and displays, as previously disclosed herein.

[0124] Stereotactic Histolysis Another embodiment for histotripsy targeting uses a stereotactic approach. Similar to the approach described in FIG. 2 above with a surgical guidance system, targeting using stereotactic histotripsy also relies on a prior MRI or CT scan of the patient and may, but does not require, real-time imaging. However, stereotactic histotripsy requires a stereotactic frame for targeting. FIG. 3 illustrates one embodiment of a stereotactic histotripsy treatment system that may include a treatment bed 0, a stereotactic frame 1, a histotripsy transducer 3, and one or more fiducial markers 4. Referring to FIG. 3, the stereotactic frame 1 is mounted on the treatment bed and the histotripsy transducer is attached to the stereotactic frame. The histotripsy transducer must be in a fixed position relative to the stereotactic frame, so the position / orientation of the histotripsy transducer with respect to the position of the stereotactic frame is always known.

[0125] In most instances, the stereotactic frame may be rigidly attached to the patient's head or torso depending on the target tissue mass. Prior to treatment, an MRI or CT scan of the patient and the target tissue mass may be acquired in the stereotactic frame. Since the stereotactic frame includes fiducial markers that are detectable by MRI or CT, these fiducial markers are imaged in pre-treatment and / or intra-treatment MRI or CT scans (see fiducial markers 4 in FIG. 4A). Based on these scans, the location of the fiducial markers relative to the tumor site T may be identified based on the location of the fiducial markers (see FIG. 4B). And since the histotripsy transducer is mechanically attached to the stereotactic frame, the location of the histotripsy transducer and focal point for and relative to the fiducial markers on the stereotactic frame is known. Once these conditions are met, the robotic positioning control system, which controls the histotripsy transducer and its position, location and movement, as well as the histotripsy system software, calculates or determines the location of the current histotripsy focal point F for the target tissue mass and the target / region of interest. decision (See FIG. 4C.) A robotic positioning system can then be used to move the treatment transducer to align the tissue ablation focus with the target site.

[0126] When the target tissue mass is a tumor, the location of the tumor border is specified with its outline and contour on a pre-treatment or intra-treatment MRI or CT scan, and the tumor border coordinates for the reference markers and the current tissue disruption focus can be calculated by the robotic positioning and tissue disruption system. As described above, the system can be configured to allow the user to define positive and negative treatment margins (e.g., positive margins extend outside the tumor or negative margins treat within the clot) and the extent of the margins (e.g., 1 cm). Once the treatment margins are defined, the system can calculate and create 3D grid sites that cover the target tissue mass and display the 3D grid sites superimposed on the patient's pre-MRI / CT scan. If the user believes that adjustments to the grid sites are necessary, adjustments to the treatment margins or coordinates can be made on the fly. In some embodiments, adjustments can be made using elasticity and deformation models to further visualize the grid and planning group sites in the most clinically relevant image sets. Once the user confirms the coordinates, the 3D grid site coordinates are sent to the robotic positioning system and software to move the histotripsy transducer appropriately to deliver the treatment according to a predefined plan including, but not limited to, patterns, paths, and prescribed cooling and / or off-times to manage heat or other undesirable tissue effects at the anterior focus. In addition to robotic mechanical delivery, the system may use electronic focus steering, in part or in whole, to achieve the desired plan, including treatment planning steps (e.g., test pulses) and / or the procedure itself (e.g., maximum volume ablation).

[0127] Catheterization targeting Some treatments require the insertion of a catheter or needle. One example is the treatment of intracerebral hemorrhage, where catheters are commonly used to drain blood clots that have been liquefied by a histotripsy procedure. In this example, a catheter or needle is inserted into the target tissue. The insertion of the needle or catheter can be guided by a surgical guidance system or by some form of imaging routinely performed in clinical practice. To guide the catheter or needle during the procedure, the tip of the catheter or needle relative to the boundaries of the target tissue mass should be identified at the insertion point. In one embodiment, the tip of the catheter or needle can include an acoustic detector and / or source configured to receive or emit and / or measure ultrasonic signals from the histotripsy transducer, respectively. Alternatively, the catheter or needle can include fiducial markers. These ultrasonic signals or fiducial markers can be used to determine the location of the target tissue mass relative to the location of the histotripsy transducer. A robotic positioning system controlling the movement of the histotripsy transducer can then calculate the coordinates of the catheter tip, and thus the histotripsy transducer or focal point, relative to the target tissue. The robotic positioning system can then calculate the translation coordinates necessary to align the tissue ablation focal point with the target tissue mass. Treatment margins can be calculated and adjusted as described above. Furthermore, if an intra-procedural image set (MRI or CT) is acquired that includes the catheter site, the robotic encoder position data can be used to further register this data stream with the acoustic data to further improve registration accuracy.

[0128] Targeting by Marker Insertion For cases not requiring catheter or needle insertion, standard markers can also be implanted in or near the target tissue mass during biopsy. These standard markers can then be visualized by MRI or CT. These markers are preferably ultrasound reflective, allowing the histotripsy transducer to receive acoustic reflection signals from these markers and determine their location during the procedure. In this way, the histotripsy procedure system can determine the coordinates of the current histotripsy focus relative to the standard markers in real time. Based on the location of the markers relative to the target tissue mass, treatment margin coordinates for the current histotripsy focus are calculated. The target tissue mass can then be treated using the techniques described above.

[0129] Referring to FIG. 5, a flowchart 500 is provided illustrating the steps of several representative embodiments for performing tissue ablation targeting and treatment using the system components described above, including a tissue ablation treatment transducer, a robotic positioning system, and / or a surgical guidance system.

[0130] At step 502 of flowchart 500, the method may include inserting a standard marker or acoustic detector into the patient near the tissue mass. As described above, in some embodiments, the surgical procedure may include inserting a catheter or needle near the target tissue site. The catheter or needle may include, for example, a standard marker disposed thereon or therein, as described above. Alternatively, the catheter or needle may include an ultrasound sensor or transmitter. In an alternative embodiment, a standard marker or acoustic sensor / transmitter may be injected into the patient's tissue in or near the target tissue site.

[0131] Next, at step 504 of flowchart 500, the method may include locating the target tissue mass relative to the location of the histotripsy transducer. In some embodiments, locating the target tissue mass may include transmitting ultrasonic energy from the histotripsy transducer to a needle or catheter within the tissue that includes an ultrasonic sensor. Signals received by the ultrasonic sensor may indicate the location of the target tissue mass relative to the histotripsy transducer. decision In other embodiments, fiducial markers on the needle or catheter, or alternatively fiducial markers injected into the tissue, may be used to correlate the coordinate system of the histotripsy system and / or surgical guidance system to the location of the target tissue mass.

[0132] In some implementations, the surgical guidance system or subsystem can identify the location of the histotripsy transducer focal point. In some examples, the surgical guidance can use the location and orientation of the histotripsy transducer itself in combination with the focal length of the transducer to determine the location of the focal point. decisionA number of techniques can be used to identify the location of the histotripsy transducer focal point, including placing standard markers (e.g., optical, electrical, or magnetic) on the transducer and identifying these standard markers with the surgical guidance system. By placing standard markers on the histotripsy ultrasound transducer that can be detected by the surgical guidance system, the location of the histotripsy transducer can be recognized in the coordinate system of the surgical guidance system. In one example, the standard markers can include a set of markers with a configuration that is unique to a known tool / instrument. A unique marker configuration (e.g., five spherical optical markers arranged in a specific pattern, such as the optical tracking markers for the Stealth Station or Brainlab surgical guidance systems) can be attached to the surface of the histotripsy transducer that can be detected by the surgical guidance system (e.g., by imaging or sensing the markers). The surgical guidance system can then automatically locate and identify the histotripsy focal point site in the surgical guidance system coordinates based on the location / orientation of the marker configuration and the histotripsy transducer focal length. In another embodiment, given the known geometry of the transducer and the predicted focal length, the in-procedure scan can be used to predict the location using the robot position encoder data (and pose relative to the image set) to predict the final bubble cluster location.

[0133] Next, in step 506 of flowchart 500, the surgical guidance system, or robotic positioning system that controls the position and motion / movement of the histotripsy transducer, can calculate the translation coordinates required to set the histotripsy focal point at the target tissue mass. These translation coordinates can then be input into the robotic positioning system to appropriately move the histotripsy transducer to align the base / tool ​​coordinate system. In some embodiments, a software supervisor can monitor the position and orientation to verify that the planned and actual site / location are accurate.

[0134] At step 508, when the histotripsy transducer is in the proper position (e.g., the focal point is located at or within the target tissue mass as verified using the recorded real-time and virtual imaging data), a histotripsy procedure may be applied to the target tissue mass by the histotripsy procedure transducer. Typically, the target tissue is a mass, such as a tumor or a blood clot mass. To treat the target mass, a user may specify the outer line and contour of the boundary of the target tissue mass on a high-resolution MRI / CT scan. For example, the surgical guidance system may include input features for the user to define a positive margin (e.g., a treatment margin that extends outside or is larger than the target tissue mass, such as treating a cancerous tumor) or a negative margin (e.g., a treatment margin that is within or is smaller than the target tissue mass, such as treating a blood clot) and the extent of the treatment margin (e.g., 1 cm). For example, if a tumor is the target tissue mass, the treatment margin may cover the entire tumor, including a margin around the tumor predefined by the user, to ensure that all tumor cells are treated. For example, if a blood clot is the target tissue mass, the treatment margin can cover most of the clot but leave an edge of the clot untreated to prevent damage to surrounding normal tissue as defined by the user. After the treatment margin is defined, the surgical guidance system or robotic arm can calculate and generate treatment parameters to cover the target tissue mass and display the treatment margin overlaid on the patient's prior MRI / CT scan. Fine-tuning or further adjustments of the treatment margin or coordinates can be made if desired by the user. The treatment margin site coordinates are then sent to the robotic control system to move the tissue disruption transducer appropriately, including according to the desired path, pattern, direction, and sequence, and to prevent non-target tissue effects. decision Therapy can be accomplished, including controlled cooling and / or off-time. These parameters can further be displayed through one or more user interfaces and displays as previously disclosed herein.

[0135] Additional Imaging and Treatment Planning Features In some instances, the surgical guidance system may include a modeling tool that may be used to capture boundary mesh coordinates of the target tissue mass from a pre-treatment MRI or CT scan. These mesh coordinates may be used directly to calculate 3D grid points of the treatment margin that may be overlaid on the pre-treatment MRI or CT scan. Alternatively, these mesh coordinates may be sent to a robotic arm to calculate the 3D grid points and / or to a histotripsy procedure control system to provide electronic focus steering coordinates / commands to cover the target tissue and treatment margins.

[0136] High and low resolution images Alignment The surgical guidance system can then be used to measure the distances between anatomical landmarks on the MRI or CT scan. For example, the surgical guidance system can measure the distances on different axes from the center of the target tissue mass and the border of the target mass. These distance values ​​can be sent to the robotic arm to calculate an upper limit that can limit the maximum distance that can be used as a steering distance to treat the target tissue mass.

[0137] Histotripsy destroys targeted tissue by disrupting cells through cavitation. A histotripsy ultrasound transducer may have both transmit capabilities to generate cavitation and receive signals emitted from the cavitation. Thus, a cavitation map generated in real time by the histotripsy transducer during treatment can be overlaid on a pre-treatment MRI / CT scan of the patient to ensure that the treatment is contained within the boundaries defined by the targeting. If cavitation occurs outside the outlined target mass, treatment can be stopped. With a histotripsy transducer array with transmit and receive capabilities, a 3D cavitation map (i.e., histotripsy treatment map) can be created during treatment to precisely indicate in real time the tissue site being treated with cavitation. This cavitation map can be overlaid in real time on the MRI / CT scan to allow the user to monitor the treatment in high resolution and in real time. In some instances, the treatment cavitation map can be introduced into a surgical guidance system or a robotic positioning system and / or overlaid on a pre-treatment MRI / CT scan showing the planned treatment mass.

[0138] In another example, the surgical guidance system may take MRI, CT, or other images of the same body part or anatomical landmark (e.g., head, abdomen, etc.) of the same patient, but in different orientations. Alignment Post-treatment images may be introduced to match pre-treatment images with the same imaging plan. Alignment This allows for precise alignment of the post-treatment mass with the planned treatment mass.

[0139] In the case where the target tissue mass is a moving target (e.g. abdominal organs with respiratory motion), motion may result in targeting errors in the system described above. In this example, the histotripsy implementation may be gated with the patient's breath / exhaust, so that histotripsy is applied only when the target is in a rest position with respect to the fixed focal transducer. For example, an accelerometer or other sensor may be placed on the patient's body near the target tissue mass to detect movement, and measurements from the sensor may be sent to the histotripsy treatment system. If the system detects movement above a threshold, delivery of the histotripsy treatment may be interrupted or delayed until the movement value returns below the threshold. Similarly, a simple respiratory monitor may be applied to the patient, and the respiratory data may be used by the system to deliver therapy only when the patient is in a rest position. It is also possible to ask the patient to perform a breath hold while the therapy is being achieved. If the patient is in fact ventilated during the procedure, the therapy may be achieved when the respiratory machine delivery falls below a predefined threshold. In the case where tissue ablation is accomplished by a phased array transducer and the transducer focal point is instantaneously moved via electronic steering, the tissue ablation focal point site may move with respiration and the moving target may be tracked in real time. For example, the site of the moving target may be estimated based on the output of an accelerometer or other sensors placed on the patient's body, a respiratory monitor, or a ventilator. In another example, imaging activation may be performed and the recorded real-time and virtual data may be used to plan a treatment trigger where the procedure is activated when the target is at the desired focal zone site and turned off when the target leaves the desired focal zone site.

[0140] It should be noted that when targets are based on pre-CT / MRI scans using the methods described herein, body deformations may occur. For example, the patient may be lying in a different position during treatment compared to the pre-scan. The ultrasound coupling device used to acoustically couple the histotripsy transducer to the patient's skin may also deform the patient's body. In these cases, to ensure treatment accuracy, the pre-MRI or CT scan data set is processed (e.g., rotated) and treatment with existing radiation tools may account for the deformed elastic body parts and Alignment will be done.

[0141] example Example 1 - Histotripsy targeting by a surgical guidance system. In this example, a robotic positioning system equipped with a histotripsy transducer is guided by a surgical guidance system to treat a tumor, specifically a liver tumor. Targeting can be implemented in the steps described below.

[0142] 1. Pre-CT / MRI Scan - As part of the diagnosis, the patient's abdomen may be scanned with a CT or MRI at fine resolution prior to treatment. Prior to treatment, the abdomen may be imaged with a coarse resolution surgical guidance system (e.g. ultrasound or digital camera).

[0143] 2. Identification of the target site by a surgical guidance system - A surgical guidance system may be used to identify the 3D site and boundaries of the target tumor based on a pre-CT or MRI scan. For example, a coarse resolution image taken with a surgical guidance system may be compared with a fine resolution CT or MRI image taken prior to treatment. Alignment The tumor boundary coordinates can then be known and calculated by the surgical guidance system.

[0144] 3. Identifying the histotripsy transducer site - A standard sensor can be placed at a fixed site on or near the histotripsy treatment transducer that is detectable by the surgical guidance system. The surgical guidance system then knows the coordinates of the histotripsy transducer and uses these coordinates to locate the site of the histotripsy focus. decision do.

[0145] 4. Aligning the histotripsy focal spot to the target tissue mass - Based on the above coordinates, the translation coordinates required to move the histotripsy transducer to align the histotripsy focal spot to a central location within the target tissue mass can be calculated by the surgical guidance system or a robotic positioning system that moves the histotripsy transducer, and the robotic positioning system can be configured to move the histotripsy transducer to align the histotripsy focal spot to the target tissue mass.

[0146] 5. Creation of 3D grid coordinates for targeting tumor mass including treatment margins - A user of the system can identify the tumor borders in each slice or image of a pre-MR or CT scan. The user can also input the desired treatment margin (e.g., 1 cm margin from the tumor border). The surgical guidance system or robotic positioning system can then calculate and create 3D grid sites that cover the entire tumor including the desired 1 cm treatment margin surrounding the tumor. The surgical guidance system or robotic positioning system can then display the 3D grid sites superimposed on the patient's pre-MRI / CT scan. The 3D grid site coordinates are then sent to the robotic positioning system to move the tissue ablation transducer appropriately during treatment.

[0147] EXAMPLE 2 - As detailed in Example 1, the guidance system, tissue disruption system, and robotic delivery system are all configured as a single integrated electro-mechanical software control system and form factor.

[0148] EXAMPLE 3 - As detailed in Examples 1 and 2, pre-treatment MRI / CT is acquired with a coupled solution at the patient site so that observed MRI / CT body divergence is calculated and understood prior to planning the tissue ablation / treatment.

[0149] Example 4 - Stereotactic Histotripsy. In this example, stereotactic histotripsy is used to target a brain tumor. Targeting is implemented in the steps described below.

[0150] 1. Pre-CT / MRI Scan - Prior to treatment, a stereotactic frame may be rigidly fixed to the patient's head. The stereotactic frame may include multiple (e.g., four) fiducial markers. The patient's head may be scanned by MRI or CT along with the stereotactic frame to image the target tissue mass and the fiducial markers.

[0151] 2. Identification of the target site - A CT or MRI scan visualizes both the standard markers and the brain tumor, so the location of the tumor relative to the standard markers is known.

[0152] 3. Identification of the histotripsy transducer site - Because the histotripsy transducer is rigidly attached to the stereotactic frame at pre-designed attachment points, the site of the histotripsy transducer focus relative to standard markers on the stereotactic frame is fixed and known at all times.

[0153] 4. Alignment of histotripsy focus with target - Based on the coordinates of the target marker, the robotic positioning system can calculate the selected tumor center, histotripsy focus, and the translation coordinates to move the histotripsy focus to align with the central location within the tumor. The robotic positioning system can then be configured to move the histotripsy transducer to align the current histotripsy focus with the tumor center. For brain targets, ultrasound propagates through the skull, which has varying thicknesses, which introduces aberrations resulting in defocusing and reduced focal pressure. An aberration correction algorithm can be applied based on a prior CT scan to improve the focusing of the focal pressure.

[0154] 5. Create 3D grid coordinates to target tumor mass including margins - the tissue ablation focus moves to the tumor center. The user can identify the target tissue mass boundary in each image of the MR or CT scan. The user can then input the desired treatment margin (1 cm margin from the tumor border circularly cropped on the pre-MRI / CT scan). The robotic positioning system can be configured to calculate and create 3D grid sites covering the entire tumor including a 1 cm treatment margin surrounding the tumor. The robotic arm system can display the 3D grid sites superimposed on the patient's pre-MRI / CT scan.

[0155] Example 5 - Histotripsy Targeting with Catheter Insertion. In this example, histotripsy targeting is guided by catheter insertion and the target treatment mass is a blood clot in the brain for the treatment of hemorrhagic stroke or intracerebral hemorrhage (ICH). For ICH treatment, histotripsy applied from the outside of the skull can be used to rapidly liquefy the clot and a catheter inserted into the clot can be used to evacuate the clot after liquefaction. Targeting can be implemented with the steps described below.

[0156] 1. Pre-CT Scan - Prior to treatment, the patient's brain may be scanned at fine resolution with a CT or MRI.

[0157] 2. Catheter Hydrophone Insertion - A catheter hydrophone can be inserted through a burr hole in the skull into the center of the clot. Insertion can be guided by a surgical guidance system or real-time imaging. The location of the catheter tip relative to the clot boundary should be known. The catheter can include a miniature hydrophone integrated into the tip of a guidewire.

[0158] 3. Alignment of histolysis focus with target - The catheter hydrophone can be used to measure the ultrasound signal from the histolysis ultrasound array element. The signal can be used to calculate the ultrasound travel time from each histolysis array element to the catheter hydrophone. Based on the hydrophone signal, the location of the catheter tip for the current histolysis focus can be calculated and aberration correction can be performed. The robotic arm system can then use these coordinates to move the histolysis transducer to align the histolysis focus with the catheter tip.

[0159] 4. Creation of 3D grid coordinates for targeting the clot mass - The user can identify the clot borders in each image of the MR or CT scan. To avoid damage to the normal brain tissue surrounding the clot, the clinician can input the desired negative margin (e.g. liquefy the clot with tissue disruption but leave a ~5mm margin at the edge of the clot intact). The robotic positioning system can then calculate and create 3D grid sites that cover the entire clot while leaving a ~5mm clot margin to preserve the normal brain tissue surrounding the clot. The robotic positioning system can also be configured to display the 3D grid sites superimposed on the pre-MRI / CT scan.

[0160] Other Systems and Methods of Use The systems and methods described herein are related to the systems and methods described in International Application No. PCT / US2019 / 063728, filed November 27, 2019, which is incorporated herein by reference. Any of the systems described herein may be further configured to perform the methods described in International Application No. PCT / US2019 / 063728. [Explanation of symbols]

[0161] 4 Standard Markers 100 Tissue Disruption System 102 Treatment transducer 104 Imaging System 106 Display Control Panel 108 Robot Positioning Arm 110 Cart F Current tissue crushing focus T Tumor site

Claims

1. receiving a first image of a target tissue mass in a surgical guidance system; acquiring a second image of the target tissue mass with an ultrasound imaging device of the surgical guidance system; registering the first image with the second image in the surgical guidance system to correlate a first coordinate system for the first image and a second coordinate system for the second image; identifying boundary coordinates of the target tissue mass in the first image in the surgical guidance system; determining, by the surgical guidance system, focal coordinates of a focal point of the histotripsy transducer based on the encoded position and orientation of the ultrasound imaging device relative to a position and orientation of a histotripsy transducer and a focal length of the histotripsy transducer; determining translation coordinates in the surgical guidance system that set the focal point of the histotripsy transducer within the boundary coordinates of the target tissue mass in the first image; moving the focal point of the histotripsy transducer based on the translation coordinates with a robotic positioning system to position the focal point of the histotripsy transducer within the target tissue mass; A method for planning surgical guidance comprising:

2. The method of claim 1 , wherein the first image comprises a high resolution image.

3. The method of claim 2 , wherein the first image comprises a high resolution MRI image.

4. The method of claim 2 , wherein the first image comprises a high resolution CT image.

5. The method of claim 1 , wherein the second image comprises an ultrasound image.

6. The method of claim 1 , wherein the second image comprises an optical image.

7. 2. The method of claim 1 , wherein said registering the first image with the second image further comprises identifying standard regions in both the first image and the second image and correlating a coordinate system of the first image with a coordinate system of the second image using the standard regions.

8. The method of claim 1 , wherein determining focal coordinates further comprises: setting a fiducial marker on the histotripsy transducer; and identifying the fiducial marker with the surgical guidance system.

9. defining a treatment margin for the target tissue mass; calculating a 3D grid area covering the target tissue mass and the treatment margin; displaying the first and second images; Displaying the 3D grid area on the first or second image; and The method of claim 1 further comprising:

10. The method of claim 9 , wherein the treatment margin comprises a positive treatment margin that extends outside the target tissue mass.

11. The method of claim 9 , wherein the treatment margin comprises a negative treatment margin that extends into the target tissue mass.

12. The method of claim 1 , further comprising: generating a histolytic treatment map; displaying the first and second images; and overlaying the histolytic treatment map on the first or second images in real time.

13. The method of claim 1 , wherein the robotic positioning system is capable of moving the histotripsy transducer in three degrees of freedom.

14. The method of claim 1 , wherein the robotic positioning system is capable of moving the histotripsy transducer in six degrees of freedom.

15. The method of claim 2 , wherein the first image comprises a cone beam CT image.

16. The method of claim 2 , wherein the first image comprises an extended fluoroscopic image.

17. The method of claim 1 , wherein the target tissue mass comprises a tumor.

18. The method of claim 1 , wherein the target tissue mass comprises a blood clot.

19. The method of claim 1 , wherein the target tissue mass comprises a cerebral hemorrhage.

20. A first imaging system having a first coordinate system; 1. A surgical guidance system comprising: a robotic positioning arm; a histotripsy transducer coupled to the robotic positioning arm; an ultrasound imaging system disposed within the histotripsy transducer, the ultrasound imaging system having a second coordinate system and encoded therein, the surgical guidance system being configured to determine a position and orientation of the ultrasound imaging system and the histotripsy transducer; The surgical guidance system comprising: an electronic controller operatively coupled to the first imaging system and the surgical guidance system, the electronic controller configured to register a first image of the target tissue mass from the first imaging system with a second image of the target tissue mass from the ultrasound imaging system to identify boundary coordinates of the target tissue mass, the electronic controller further configured to determine translation coordinates of the robotic positioning arm required to focus the histotripsy transducer within the target tissue mass; A treatment system comprising:

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