Minimally invasive histotripsy systems and methods

Abstract

A histotripsy therapy system 100 configured for treatment of tissue is provided that can include any number of features. Provided herein are systems and methods that provide effective non-invasive and minimally invasive therapeutic, diagnostic, and research methods. In particular, provided herein are optimized systems and methods that provide targeted and effective histotripsy in a variety of different regions and under a variety of different conditions without causing unnecessary tissue damage to intervening / non-target tissues or structures.SOLUTION: A method of treating tissue of a patient with a robotic surgical system is provided that includes identifying a target tissue location, preparing the target tissue location for histotripsy therapy with a laparoscopic subsystem of the robotic surgical system, and performing the histotripsy therapy with a histotripsy subsystem of the robotic surgical system on the prepared target tissue location.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 986,410, entitled "Minimally Invasive Historipsy Systems and Methods," filed March 6, 2020, under 35 U.S.C. § 119, the disclosure of which is incorporated herein by reference.

[0002] Incorporation by Reference

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

[0003] This disclosure details novel high intensity focused ultrasound therapy (HITU) systems configured to provide acoustic cavitation, methods, devices, and procedures for minimally invasive and non-invasive treatment of healthy, diseased, and / or injured tissue. The acoustic cavitation systems and methods described herein, also known as histotripsy, may include transducers, drive electronics, positioning robots, imaging systems, and integrated treatment planning and control software to provide comprehensive treatment and therapy of a patient's soft tissues. [Background technology]

[0004] Histotripsy, or pulsed ultrasound cavitation therapy, is a technique in which very short, intense bursts of acoustic energy produce controlled cavitation (microbubble formation) within a focal volume. The violent expansion and collapse of these microbubbles mechanically homogenizes the cells and tissue structures within the focal volume, an end result that is quite different from the coagulation necrosis characteristics of thermal ablation. Operating within the realm of non-thermal histotripsy requires the delivery of acoustic energy in the form of high-amplitude acoustic pulses with a low duty cycle.

[0005]

[0005] Compared to conventional focused ultrasound techniques, histotripsy has the following important advantages: 1) the destruction process at the focal point is mechanical rather than thermal; 2) cavitation appears bright on ultrasound imaging, thereby confirming proper targeting and localization of the treatment; 3) treated tissue generally, but not always, appears darker (more hypoechoic) on ultrasound imaging so the operator can see what has been treated; and 4) histotripsy produces damage 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) cryotherapy or radiation, histotripsy relies on the mechanical action of cavitation to destroy tissue, and does not rely on heat, cold, or ionizing energy. Summary of the Invention

[0006]

[0006] A method for treating tissue of a patient using a robotic surgical system is provided, comprising the steps of identifying a target tissue location using an imaging subsystem of the robotic surgical system, preparing the target tissue location for tissue disruption treatment using a laparoscopic subsystem of the robotic surgical system, and performing tissue disruption treatment on the prepared target tissue location using the tissue disruption subsystem of the robotic surgical system.

[0007] In some embodiments, the imaging subsystem comprises an endoscopic robotic system; Includes ultrasound imaging systems, CT imaging systems, cone CT imaging systems, extended or enhanced multi-modality imaging systems, and / or fluoroscopic imaging systems.

[0008] In some embodiments, the imaging subsystem includes an imaging device disposed on a robotic arm of the robotic surgical system.

[0009] In one embodiment, preparing the target tissue location further includes ablating intervening tissue between the exterior surface of the patient and the target tissue location.

[0010]

[0010] In another embodiment, the target tissue location further includes a hollow / lumen body organ, duct or lumen, and the step of preparing the target tissue location further includes the step of fluidizing the target tissue location with the laparoscopic subsystem to form an acoustic window within the target tissue location and / or the pathway to the target tissue location.

[0011]

[0011] In some embodiments, the step of administering the histolytic treatment further includes dissolving or liquefying the targeted tissue location.

[0012]

[0012] In one embodiment, the target tissue location includes a first tissue structure and a second tissue structure, and the step of performing tissue disruption treatment further includes a step of dissolving or liquefying the first tissue structure but not dissolving or liquefying the second tissue structure.

[0013] In one embodiment, the first tissue structure comprises soft tissue, cancerous tissue, tumor tissue, a blood vessel, or a duct, including a bile duct.

[0014]

[0014] In one embodiment, the step of performing tissue disruption further includes the steps of assessing a cavitation threshold at one or more locations within the target tissue location and optimizing tissue disruption treatment parameters based on the assessed cavitation threshold.

[0015] In some embodiments, the histotripsy subsystem is located on a robotic arm with three or more degrees of freedom.

[0016] In one embodiment, the robotic surgical system includes a cart / column-based surgical system.

[0017] In another embodiment, the robotic surgical system includes a bed-based surgical system.

[0018]

[0018] A surgical system is provided that includes at least one imaging subsystem configured to identify a target tissue location on a patient, a laparoscopic subsystem disposed on at least one robotic arm of the surgical system, the laparoscopic subsystem configured to prepare the target tissue location for tissue disruption treatment, and a tissue disruption subsystem disposed on at least one robotic arm of the surgical system, the tissue disruption subsystem configured to perform tissue disruption treatment at the prepared target tissue location.

[0019] In some embodiments, the imaging subsystem includes an endoscopic robotic system, an ultrasound imaging system, a CT imaging system, a cone CT imaging system, an extended or enhanced multi-modality imaging system, and / or a fluoroscopic imaging system.

[0020]

[0020] A method for treating tissue of a patient with a robotic surgical system is provided, comprising the steps of identifying a target tissue location with an imaging subsystem of the robotic surgical system, preparing the target tissue location for surgery with a tissue disruption subsystem of the robotic surgical system, and performing surgery at the prepared target tissue location with a laparoscopic subsystem of the robotic surgical system.

[0021] In some embodiments, the imaging subsystem includes an endoscopic robotic system, an ultrasound imaging system, a CT imaging system, cone CT imaging, an extended or enhanced multi-modality imaging system, and / or a fluoroscopic imaging system.

[0022] In some embodiments, the imaging subsystem includes an imaging device disposed on a robotic arm of the robotic surgical system.

[0023]

[0023] In one embodiment, preparing the target tissue further includes skeletonizing soft tissue within the target tissue location with a tissue disruption subsystem.

[0024]

[0024] In some embodiments, the step of preparing the target tissue location for surgery by the tissue disruption subsystem further includes the steps of assessing a cavitation threshold at one or more locations within the target tissue location, optimizing tissue disruption treatment parameters based on the assessed cavitation threshold, and performing the tissue disruption treatment to dissolve or liquefy only a first tissue structure at the target tissue location and not to dissolve or liquefy a second tissue structure at the target tissue location.

[0025] In one embodiment, the first tissue structure comprises soft tissue, cancerous tissue, tumor tissue, a blood vessel, or a duct, including a bile duct.

[0026] In some embodiments, the histotripsy subsystem is located on a robotic arm with three or more degrees of freedom.

[0027] In some embodiments, the robotic surgical system includes a cart / column-based surgical system.

[0028] In another embodiment, the robotic surgical system includes a bed-based surgical system.

[0029] In some embodiments, performing the surgical procedure further includes resecting one or more tissues at the target tissue location with the laparoscopic subsystem. In one embodiment, the resecting further includes energy-based cutting, performing a sealing and / or using a ligating device, using a monopolar or bipolar device, performing internal stapling and / or internal clipping.

[0030] In one embodiment, the target tissue location includes liver, kidney, pancreas, head / neck, thyroid, spleen, prostate, heart, lung, central or peripheral vasculature, spinal cord and / or brain tissue.

[0031] In some embodiments, the surgical procedure further comprises dividing one or more lobes or segments of the liver.

[0032] In one embodiment, divided lobes or segments of the liver are removed from the body.

[0033]

[0033] A surgical system is provided that includes at least one imaging subsystem configured to identify a target tissue location on a patient, a tissue disruption subsystem disposed on at least one robotic arm of the surgical system and configured to prepare the target tissue location for surgery, and a laparoscopic subsystem disposed on at least one robotic arm of the surgical system and configured to perform surgery at the prepared target tissue location.

[0034] In some embodiments, the imaging subsystem includes an endoscopic robotic system.

[0035] In one embodiment, the imaging subsystem includes an ultrasound imaging system.

[0036] In another embodiment, the imaging subsystem includes a CT imaging system.

[0037] In some embodiments, the imaging subsystem includes an extended or enhanced multi-modality imaging system.

[0038] In another embodiment, the imaging subsystem includes a fluoroscopic imaging system.

[0039]

[0039] A method for treating tissue with a robotic surgical system is provided, comprising the steps of accessing a target hollow organ location with an endoscopic robotic system of the robotic surgical system, fluidizing the target hollow organ location to form an acoustic window within the target hollow organ location, and performing tissue disruption treatment on the fluidized target hollow organ location with a tissue disruption subsystem of the robotic surgical system.

[0040] In some embodiments, the target hollow organ comprises the lung or colon.

[0041]

[0041] In some embodiments, fluidizing the target hollow organ site comprises fluidizing the target hollow organ site with an endoscopic robotic system.

[0042]

[0042] In one embodiment, the method further includes performing the accessing, fluidizing and administering steps under real-time imaging guidance.

[0043] In one embodiment, the real-time imaging guidance includes CT, fluoroscopy and / or cone beam CT data / imaging.

[0044] In one embodiment, the real-time imaging guidance includes ultrasound imaging.

[0045]

[0045] A method for treating tissue with a robotic surgical system is provided, comprising the steps of accessing a target hollow organ location with a laparoscopic robotic system of the robotic surgical system, fluidizing a body cavity adjacent to the target hollow organ location to form an acoustic window to the target hollow organ location, and performing tissue disruption treatment at the target hollow organ location with a tissue disruption subsystem of the robotic surgical system.

[0046] In some embodiments, the target hollow organ comprises the lung or colon.

[0047] In one embodiment, fluidizing the body cavity includes fluidizing the body cavity with a laparoscopic robotic system.

[0048]

[0048] In another embodiment, the method further includes performing the accessing, fluidizing, and administering steps under real-time imaging guidance.

[0049] In some embodiments, the imaging subsystem includes an endoscopic robotic system, an ultrasound imaging system, a CT imaging system, a cone CT imaging system, an extended or enhanced multi-modality imaging system, and / or a fluoroscopic imaging system.

[0050]

[0050] In one embodiment, the method further includes a step of fluidizing the target hollow organ location to form an acoustic window within the target hollow organ location, and a step of performing tissue disruption treatment within the fluidized target hollow organ location by the tissue disruption subsystem.

[0051] In some embodiments, the target organ location is visualized in real time using one or more modalities including ultrasound, X-ray based imaging and / or optical imaging.

[0052] In one embodiment, the location of the tissue ablation focus may be updated based on feedback provided by real-time imaging guidance.

[0053]

[0053] In another embodiment, an endoscopic / laparoscopic robot uses two or more robotic arms to simultaneously enable real-time imaging guidance, manipulation of one or more surgical instruments / tools, and the position of a tissue disruption treatment transducer.

[0054] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: [Brief explanation of the drawings]

[0055] [Figure 1A]

[0055] FIG. 1 illustrates an ultrasound imaging and therapy system. [Figure 1B] FIG. 1 illustrates an ultrasound imaging and therapy system. [Figure 2A]

[0056] FIG. 1 illustrates a bronchoscopy robot cooperating with a non-invasive tissue disruption robot. [Figure 2B]

[0057] FIG. 1 illustrates a bronchoscopy robot collaborating with a non-invasive tissue disruption robot in a cone beam CT environment. [Figure 3A]

[0058] FIG. 1 illustrates a multi-approach for the lungs, including a laparoscopic / endoscopic robot and a separate tissue disruption bedside robotic cart. [Figure 3B]

[0059] FIG. 1 illustrates a laparoscopic / endoscopic robot that can be used with non-invasive tissue disruption. [Figure 4]

[0060] FIG. 1 illustrates a multi-approach for pancreatic / liver resection that can be bed or patient-side cart-based. DETAILED DESCRIPTION OF THE INVENTION

[0056]

[0061] The disclosed systems, methods, and devices are useful in open surgery, minimally invasive surgery (laparoscopic and percutaneous), robotic surgery (integrated into robotic-enabled medical systems), endoscopic or fully percutaneous extracorporeal non-invasive acoustic cavity surgery for the treatment of healthy, diseased, and / or injured tissue, including, but not limited to, tissue destruction, cutting, skeletonization, and ablation. Acoustic cavitation can be used for tissue disruption. Due to its tissue-selective properties, tissue disruption can also be used to form cytoskeleton that allows subsequent tissue regeneration, either de novo or through the application of stem cells and other adjuvants. Finally, tissue disruption can be used to induce the release of delivered agents, such as chemotherapy and immunotherapy, by locally inducing drug release through the application of acoustic energy to a target. As described below, acoustic cavitation systems can include various subsystems, including carts, therapy, integrated imaging, robotics, couplings, and software. Systems can also include various other components, ancillaries, and accessories, including, but not limited to, computers, cables and connectors, networking devices, power supplies, displays, drawers / compartments, doors, wheels, and various simulation and training tools. All systems, methods, and means for generating, controlling, and implementing tissue disruption, including the new related inventions disclosed herein, are considered part of this disclosure.

[0057]

[0062] 1A generally illustrates a histotripsy system 100 according to the present disclosure, including a therapy transducer 102, an imaging system 104, a display and control panel 106, a robotic positioning arm 108, and a cart 110. The system may further include an ultrasound coupling interface and a coupling medium source, not shown.

[0058]

[0063] 1B is a bottom view of the therapy transducer 102 and imaging system 104. As shown, the imaging system may be positioned at the center of the therapy transducer. However, other embodiments may include an imaging system located elsewhere within the therapy transducer or integrated directly into the therapy transducer. In some embodiments, the imaging system is configured to generate real-time imaging at the focal point of the therapy transducer. The system also allows for the placement of multiple imaging transducers within the therapy transducer to simultaneously provide multiple views of the target tissue and combine those images into a single 3D image.

[0059]

[0064] The histotripsy system may include one or more of a variety of subsystems, including a treatment subsystem capable of generating, applying, focusing, and implementing acoustic cavitation / histotripsy via one or more treatment transducers; an integrated imaging subsystem (or connection to the integrated imaging subsystem) that allows for real-time visualization of the treatment site and histotripsy effects throughout the procedure; a robotic positioning subsystem that connects to, supports, or is further enabled to interact with the coupling subsystem to mechanically and / or electronically steer the treatment transducer and enable acoustic coupling between the treatment transducer and the patient; software for communicating, controlling, and interfacing with the system and computer-based control systems (and other external systems); and various other components, auxiliaries, and accessories, including one or more user interfaces and displays, associated guided workflows, all of which function partially or in conjunction with one another. The system may further include various fluidic systems and fluid management components that supply and store fluids, including, but not limited to, pumps, valves, and flow controls, temperature and degassing controls, and irrigation and aspiration functions. The system may also include various power sources and protection devices.

[0060] cart

[0065] Cart 110 may generally be configured in a variety of styles and form factors based on the particular use and procedure. In some cases, a system may include multiple carts configured with similar or different configurations. In some embodiments, the cart may be configured and arranged for use in a radiological environment, and possibly in conjunction with imaging (e.g., CT, cone beam CT, and / or MRI scans). In other embodiments, The cart can be deployed for use in operating rooms and sterile environments for open or laparoscopic surgery and endoscopic applications, or in robotic-enabled operating rooms, and can be used alone or as part of a surgical robotic procedure in which a surgical robot performs specific tasks before, during, or after use of the system and implementation of acoustic cavitation / tissue disruption. Thus, depending on the procedure environment based on the aforementioned embodiments, the cart can be positioned to provide sufficient workspace and access to various anatomical regions of the patient (torso, abdomen, flank, head and neck, etc.) as well as workspace for other systems (e.g., anesthesia cart, laparoscopic tower, surgical robot, endoscopic tower, etc.).

[0061]

[0066] The cart can also interface with a patient surface (e.g., a table or bed) to allow the patient to be oriented and repositioned in numerous positions, angles, and orientations, including allowing the patient to be repositioned in multiple positions, angles, and orientations before, during, and after a procedure. The cart may further include the ability to interface 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, optical, ultrasound, image fusion, and / or image flow, to support the treatment and / or use environment, including physical / mechanical interoperability (e.g., interoperability within a cone beam CT workspace for collecting imaging data before, during, and / or after tissue disruption), and to provide access to and display of patient medical data, including but not limited to, exam data and historical medical record data.

[0062]

[0067] In some embodiments, one or more carts may be configured to work together. As an example, one cart may include a bedside mobile cart with one or more robotic arms that can be used with therapy transducers, therapy generators / amplifiers, etc., while a companion cart that is associated with it and located remotely from the patient may include built-in imaging and a console / display for controlling the robot and therapy surfaces, such as in a surgical robot and master / slave configuration.

[0063]

[0068] In some embodiments, the system may include multiple carts, all slaved to one master cart and equipped to perform acoustic cavitation procedures. In some configurations, one cart configuration may allow for storage of specific subsystems at a distance to reduce congestion in the operating room, while another associated cart may primarily contain bedside subsystems and components (e.g., delivery systems and treatment components).

[0064]

[0069] Many permutations and configurations of cart design can be envisioned, and these examples in no way limit the scope of the present disclosure.

[0065] Tissue disruption

[0070] Histotripsy involves short, high-amplitude focused ultrasound pulses to generate a dense, intense "bubble cloud" capable of targeted fragmentation and destruction of tissue. When directed at tissue interfaces, including tissue / fluid interfaces, histotripsy can produce controlled tissue erosion, and when bulk tissue is targeted, it can produce well-defined tissue fragmentation and destruction at the subcellular level. Unlike other forms of ablation, including cryo- and radiation-based modalities, histotripsy does not rely on thermal or ionizing energy for tissue treatment. Instead, histotripsy uses acoustic cavitation generated at the focal point to mechanically affect tissue structure and, in some cases, liquefy, suspend, solubilize, and / or destroy tissue into subcellular components.

[0066]

[0071] Histotripsy can be applied in various forms, including: 1) intrinsic threshold tissue disruption ( Intrinsic-Threshold Histotripsy: To induce cavitation in a medium, one to two pulses of high-amplitude negative / tensile phase pressure (e.g., approximately 24–28 MPa for aqueous soft tissue) are delivered. 2) Shock-Scattering Histotripsy: To induce cavitation in a medium, a pulse of typically three to 20 cycles is delivered. The shock waves (positive / compression phase) scattered from the initial individual microbubbles form counter shock waves, which constructively interfere with the incident negative / tensile phase to form high-amplitude negative / tensile phases above the intrinsic threshold. This produces clusters of cavitation microbubbles. The amplitude of the tensile phase of the pulse is sufficient to induce bubble nuclei within the medium, which undergo inertial cavitation within the focal zone for the duration of the pulse. These nuclei scatter the incident shock wave, which then reverses and constructively interferes with the incident shock wave, exceeding the intrinsic nucleation threshold. 3) Boiling Histotripsy: Employs pulses of approximately 1 ms to 20 ms duration. Absorption of the shock pulse rapidly heats the medium, thereby lowering the intrinsic threshold. When this intrinsic threshold coincides with the peak negative pressure of the incident wave, a boiling bubble forms at the focus.

[0067]

[0072] The large pressure generated at the focal point causes the formation of a cloud of acoustic cavitation bubbles above a certain threshold, thereby producing localized stresses and strains in the tissue and mechanical disruption without significant thermal welding. Minimal effects are observed on the tissue at the focal point at pressure levels where cavitation does not occur. This cavitation effect is observed only at pressure levels significantly greater than those that define the inertial cavitation threshold in water for similar pulse durations, at peak negative pressures of approximately 10 MPa to 30 MPa.

[0068]

[0073] Histotripsy can be performed in multiple ways and with different parameters. Histotripsy can be performed completely non-invasively by acoustically coupling a focused ultrasound transducer onto the patient's skin and transmitting acoustic pulses transcutaneously through the overlying (and intervening) tissue to the focal area (treatment zone and site). Histotripsy applications are not limited to percutaneous techniques and can be applied by any means that allows for contact between tissue and the transducer, including open, laparoscopic, percutaneous, and robotic surgical procedures. Given that the bubble cloud resulting from histotripsy is observable, for example, as a highly dynamic echogenic region on B-mode ultrasound images, and its use (and associated procedures) allows for continuous visualization, histotripsy can be further targeted, planned, directed, and observed under direct visualization by ultrasound imaging. Similarly, treated and fragmented tissue exhibits dynamic changes (typically decreases) in echogenicity, which can be used to assess, plan, observe, and monitor treatment.

[0069]

[0074] Typically, in histotripsy, an ultrasound pulse of one or more acoustic cycles is applied, and bubble cloud formation relies on the pressure-relief scattering of a positive shock front (sometimes exceeding 100 MPa, P+) from an initial set of sparsely distributed bubbles (or even a single bubble), referred to as the "shock scattering mechanism."

[0070]

[0075] This mechanism relies on a single (or a few sparsely dispersed) bubble being generated by the initial negative half-cycle of the pulse at the transducer focal point. A cloud of microbubbles then forms due to the pressure-relief backscattering of the high-peak positive shock front from these sparsely generated bubbles. These backscattered high-amplitude rarefaction waves exceed the intrinsic threshold, thus generating a localized dense bubble cloud. Each subsequent acoustic cycle then induces further cavitation by backscattering from the bubble cloud front growing toward the transducer. As a result, an elongated dense bubble cloud is observed growing along the acoustic axis, opposite to the direction of ultrasound propagation, due to the impact scattering mechanism. This impact scattering process makes bubble cloud generation dependent not only on the peak negative pressure, but also on the number of acoustic cycles and the amplitude of the positive shock. Nonlinear propagation In the absence of at least one strong shock front caused by seeding, a dense bubble cloud is not generated when the peak negative half-cycle is below an intrinsic threshold.

[0071]

[0076] If fewer than two cycles of ultrasound pulses are applied, impact scattering can be minimized, and the generation of a high-density bubble cloud depends on the negative half-cycle of the applied ultrasound pulse exceeding the "intrinsic threshold" of the medium, which we refer to as the "intrinsic threshold mechanism."

[0072]

[0077] This threshold can range from 26 MPa to 30 MPa for soft tissues with high water content, such as those in the human body. In some embodiments, this intrinsic threshold mechanism can be used to make the spatial extent of damage clearer and more predictable. Peak negative pressures (P-) not significantly higher than this threshold can produce reproducible sub-wavelength damage as small as half the -6 dB beamwidth of the transducer.

[0073]

[0078] High-frequency histotripsy pulses result in smaller minimum reproducible lesion sizes, which is advantageous in applications requiring precise lesion generation. However, high-frequency pulses are more susceptible to attenuation and distortion, making them problematic at deeper penetration depths (e.g., ablation deep within the body) or through distortion-prone media (e.g., transcranial procedures or procedures in which pulses are delivered through bone). Histotripsy can also be applied as a low-frequency "pump" pulse (typically <2 cycles and having a frequency between 100 kHz and 1 MHz) in conjunction with a high-frequency "probe" pulse (typically <2 cycles and having a frequency above 2 MHz or in the range between 2 MHz and 10 MHz), where the peak negative pressures of the low-frequency and high-frequency pulses constructively interfere to exceed intrinsic thresholds in the target tissue or medium. Low-frequency pulses, which are more resistant to attenuation and distortion, can increase peak negative pressure P- levels over a region of interest (ROI), while high-frequency pulses, which offer finer precision, can pinpoint target sites within the ROI and increase peak negative pressure P- above intrinsic thresholds. This approach is sometimes referred to as "dual-frequency," "dual-beam histotripsy," or "parametric histotripsy."

[0074]

[0079] Included herein as part of the systems and methods disclosed herein are additional systems, methods, and parameters for implementing optimized tissue disruption using impact scattering, intrinsic thresholds, and various parameters enabling frequency compounding and bubble manipulation, including additional means for controlling the tissue disruption effects described above with respect to steering and positioning of the focal spot while simultaneously managing tissue effects (e.g., pre-focused thermal collateral damage) at the treatment site or within intervening tissue. Also disclosed as part of the present disclosure, including future envisioned embodiments, are various systems and methods that may include multiple parameters, including, but not limited to, frequency, operating frequency, center frequency, pulse repetition frequency, pulses, bursts, number of pulses, cycles, pulse length, pulse amplitude, pulse duration, delay, burst repetition frequency, sets thereof, multiple sets of loops, multiple and / or different sets of loops, sets of loops, and various combinations or permutations thereof.

[0075] Treatment Components

[0080] The treatment subsystem may cooperate with other subsystems for generating, optimizing, implementing, visualizing, monitoring, and controlling acoustic cavitation, also referred to herein and hereafter as "tissue disruption," and its derivatives, including boiling tissue disruption and other thermal high-frequency ultrasound techniques. It is noted that the disclosed invention may also be beneficial to other acoustic treatments that do not include cavitation, mechanical, or tissue disruption components. The treatment subsystem may include, among other features, an ultrasound treatment transducer and pulse generator system configured to deliver ultrasound waves into tissue.

[0076]

[0081] To generate and perform tissue disruption and derivatives of tissue disruption, the treatment subsystem may also include components including, but not limited to, one or more function generators, amplifiers, treatment transducers, and power sources.

[0077]

[0082] Therapy transducers may include a single element or multiple elements configured to be excited by high-amplitude electrical pulses (>1000 V or any other voltage capable of causing damage to a living organism). The amplitude required to drive a therapy transducer for tissue ablation varies depending on the transducer design and material used (e.g., solid or polymer / piezoelectric composites, including ceramic or single crystals), as well as the transducer center frequency, which is directly proportional to the thickness of the piezoelectric material. Thus, transducers operating at high frequencies require lower voltages to generate a given surface pressure than those required by lower-frequency therapy transducers. In some embodiments, the transducer elements are formed using piezoelectric polymer composites or solid piezoelectric materials. The piezoelectric material may also be of polycrystalline / ceramic or single-crystal structure. In some embodiments, the transducer elements may be formed using silicon using MEMs technology, including CMUT and PMUT designs.

[0078]

[0083] In some embodiments, the function generator may comprise a field programmable gate array (FPGA) or other suitable function generator, which may be configurable using the parameters disclosed herein above, including but not limited to, frequency, pulse repetition frequency, burst, number of bursts which may comprise pulses, number of pulses, pulse length, pulse duration, delay, burst repetition frequency or duration, where a set of bursts may comprise a set of parameters, where a set of loops may comprise different sets of parameters, with or without delay or with different delays, where different time delays may occur, where multiple independently controlled loop sets may be repeated and / or new loop sets may be introduced, and various combinations and permutations thereof throughout.

[0079]

[0084] In some embodiments, the generator or amplifier can be configured as a general-purpose single-cycle or multi-cycle pulse generator, compatible with Class D or inductive drive, and across all envisioned clinical applications and environments, some of which are described later in this disclosure. In other embodiments, the Class D or inductive current driver can be configured to include a transformer and / or autotransformer drive circuit to provide additional step-up / step-down components, and possibly, preferably, to enable amplitude step-up. The generator or amplifier can also include specific protection mechanisms to further support the system and to protect other components of the system (e.g., therapy transducers and / or amplifier circuit components) and / or the user from various hazards, including, but not limited to, electrical safety hazards that could cause harm, damage, or problems to the environment, the system, and the therapy system, and the user.

[0080]

[0085] The disclosed generators may enable and support the ability for the system (via available software tools) to select, modify and control various parameters including but not limited to those disclosed above, as well as the ability to start / stop treatment, set and read voltage levels, pulse and / or burst repetition frequencies, number of cycles, duty cycles, available channels and delays, etc., modulate pulse amplitude on a fast time scale independent of the high voltage source, and / or other service, diagnostic or therapeutic functions.

[0081]

[0086] In some embodiments, the therapy subsystem and / or its components, such as amplifiers, Components may further include embedded computer processing capabilities, may be networked, connected, accessible between systems, and / or may be removable / portable, modular and / or interchangeable, and / or may be driven / commanded from / by other systems, or in various combinations. Other systems include other acoustic cavitation / histotripsy, HIFU, HITU, radiation therapy, radiofrequency, microwave and cryoablation systems, navigation and positioning systems, laparoscopic or surgical towers including open surgery, laparoscopy, single incision / single port, endoscopic and non-invasive surgical robots, other energy or viewing systems, surgical system racks or booms, imaging carts, etc.

[0082]

[0087] In some embodiments, the amplifier or amplifiers may include a class-D amplifier and associated drive circuitry including matching circuit components. Depending on the transducer element electrical impedance and the selection of matching circuit components (e.g., an LC circuit consisting of a series inductor L1 and a parallel capacitor C1), the combined impedance can be set aggressively low to provide the high amplitude electrical waveform required to drive the transducer element. The maximum amplitude of the class-D amplifier depends on the circuit components used, including the drive MOSFET / IGBT transistor, matching circuit components or inductors, and transformers or autotransformers, and may typically be in the low kV range (e.g., 1 kV to 3 kV).

[0083]

[0088] Therapeutic transducer elements are excited by an electrical waveform of amplitude (voltage) that produces sufficient pressure output for histotripsy. The excitation field can be defined as the required waveform voltage due to 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, so half the voltage is required to achieve the same electric field and surface pressure.

[0084]

[0089] The therapy subsystem may also include therapy transducers of various designs and operating parameters for use in various treatments (and treatment situations). The system may be configured with one or more therapy transducers that are further compatible with and interoperable with various aspects of similar or different systems (e.g., they may interface with a robotic arm using a common interface and exchange mechanism, or conversely, may be adapted to interoperate differently with application-specific imaging probes, where different imaging probes may interface with and integrate therapy transducers in distinctly different ways).

[0085]

[0090] Therapy transducers may be configured with a variety of parameters, which may include size, shape (e.g., rectangular or circular, anatomically curved housing, etc.), geometry, focal length, number of elements, element size, element distribution (e.g., number of rings in an annular patterned transducer, ring size), frequency, enabled electronic beam steering, etc. Transducers may be configured with a variety of materials (e.g., piezoelectric, silicon, etc.), form factors and types (e.g., machined elements, chip-based, etc.), and / or various manufacturing methods.

[0086]

[0091] Transducers can be designed and optimized for clinical applications (e.g., abdominal tumors, peripheral vascular disorders, fat ablation, etc.) and desired results (e.g., acoustic cavitation / histotripsy without thermal injury to intervening tissue), providing a wide operating range, including relatively shallow and superficial targets (e.g., thyroid or breast nodules) and deeper or hard-to-reach targets such as central liver or brain tumors. Transducers can be configured with a variety of parameters, including frequency, pulse repetition rate, pulses, number of pulses, pulse length, pulse duration, delay, repetitions, synchronization delay, synchronization period, synchronization pulse, synchronization pulse delay, various loop sets, etc. Transducers can be configured to enable acoustic cavitation / histodisruption under various parameters and sets enabled by the system components described above (e.g., function generators and amplifiers, etc.), including but not limited to these permutations. Transducers can also be designed to enable activation of drug payloads deposited within tissue by various means, including injection, placement, or delivery of micelles or nanostructures.

[0087] Embedded Imaging

[0092] The disclosed systems may include various imaging modalities that allow users to visualize, monitor, and collect / use feedback on the patient's anatomy, associated regions of interest and treatment / treatment sites, as well as surrounding and intervening tissues, to assess, plan, and perform treatment and adjust treatment parameters as needed. Imaging modalities may include various ultrasound, X-ray, CT, MRI, PET, fluoroscopy, optical, contrast-based, and / or contrast-based imaging, and / or various combinations thereof. It is further disclosed that various image processing and characterization techniques are also available to enable enhanced visualization and user decision-making. These may be selected or commanded manually by the user or automatically by the system. The systems may be configured to enable apposition, toggling, overlay, 3D reconstruction, segmentation, registration, multimodal image fusion, image flow, and / or any method that allows users to identify, define, and communicate various aspects of using imaging during treatment, displayed on various system user interfaces and displays. Examples may include, by way of non-limiting example, locating, displaying, and characterizing potential treatment sites within, on, and / or around an area of ​​interest, organ system, organ or tissue, critical structures such as ducts, blood vessels, nerves, ureters, fissures, capsules, tumors, tissue damage / injury / disease, other organs, connective tissue, etc., and / or identifying the relationship of one or more of these to each other (e.g., tumor-draining lymph nodes or vessels, or tumors near organ capsules or other underlying organs).

[0088]

[0093] The system can be configured to include on-board built-in imaging hardware, software, sensors, probes, and wetware, and / or can be configured to communicate and interface with external imaging and image processing systems. The above components can also be integrated into the system's therapy subsystem component, where the probe, imaging array, etc. is electrically, mechanically, or electromechanically integrated with the therapy transducer. This can provide, in part, the ability to have geometrically aligned imaging and therapy, with the therapy in direct field of view, possibly along with the imaging. In some embodiments, this integration can include a fixed orientation of the imaging function (e.g., imaging probe) relative to the therapy transducer. In other embodiments, the imaging product may be able to move or adjust its own position, including modifying angle, extension (e.g., distance from the therapy transducer or patient), rotation (e.g., imaging plane in the example of an ultrasound probe), and / or other parameters, including dynamically moving / adjusting while actively imaging. The imaging component or probe can be encoded so that its orientation and position can be determined relative to the therapy transducer and / or another aspect of the system, such as a robotic-enabled positioning component.

[0089]

[0094] In one embodiment, the system may include an on-board ultrasound mechanism further configured to allow the user to visualize, monitor, and receive feedback on the treatment site via the system display and software, including enabling ultrasound imaging and characterization (and its various forms), ultrasound-guided planning, and ultrasound-guided treatment, all in real time. The system may be configured to allow the user to manually, semi-automatically, or fully automated (e.g., using hand or robotic-enabled imaging devices) It may be configured to allow imaging of the patient.

[0090]

[0095] In some embodiments, imaging feedback and monitoring may include monitoring changes in backscatter from the bubble cloud, speckle reduction in backscatter, backscatter speckle statistics, tissue mechanical properties (i.e., elastography), tissue perfusion (i.e., ultrasound imaging), shear wave propagation, acoustic emission, electrical impedance tomography, and / or various combinations thereof, including as displayed by or integrated with other forms of imaging (e.g., CT or MRI).

[0091]

[0096] In some embodiments, imaging, including feedback and monitoring from backscatter from the bubble cloud, can be used as a method to instantly determine whether the tissue disruption process has been initiated, properly maintained, or stopped. For example, this method allows for continuous real-time monitoring of drug delivery, tissue erosion, etc. This method can also provide feedback that allows the tissue disruption process to be initiated at higher intensities and maintained at significantly lower intensities. For example, backscatter feedback can be monitored by any transducer or ultrasound imaging device. By measuring the feedback of the treatment transducer, an auxiliary transducer can deliver interrogation pulses or be configured to passively detect cavitation. The nature of the received feedback can also be used to adjust acoustic parameters (and related system parameters) to optimize the drug delivery and / or tissue erosion process.

[0092]

[0097] In some embodiments, imaging including feedback and monitoring from backscatter and speckle reduction may be configured in the system.

[0093]

[0098] For systems that include backscatter feedback and monitoring, and as background information, as tissue is gradually mechanically fragmented—in other words, homogenized, fractured, or eroded—the size and distribution of acoustic scattering changes as a result of this process. At some point in this process, the scattering granularity and density are reduced to a level where ultrasound is barely scattered, or the amount of scattering is significantly reduced. This results in a significant reduction in speckle, the coherent constructive and destructive interference patterns of light and dark spots seen on images when a coherent illumination source, in this case ultrasound, is used. After a certain treatment time, speckle reduction results in dark areas within the treatment volume. The amount of speckle reduction is related to the amount of tissue fragmentation and can therefore be related to the size of the remaining tissue fragments. When this size is reduced to subcellular levels, it is considered that no cells remain. Therefore, treatment can proceed until the desired level of speckle reduction is achieved. Speckle is easily observed and evaluated on standard ultrasound imaging systems. Dedicated transducers and systems, including those described herein, can also be used to evaluate changes in backscatter.

[0094]

[0099] Also, for systems involving speckle feedback and monitoring, and by way of background information, images may persist from frame to frame with very little change as long as the scattering distribution remains constant and there is no subject motion. However, long before the magnitude of scattering is reduced enough to produce speckle reduction, the scattering may change enough to be detected by signal processing and other means. This family of techniques can act as detectors of changes in speckle statistics. For example, the magnitude and location of one or more speckles in the image begin to become correlated before observable speckle reduction occurs. Speckle decorrelation, after appropriate motion correction, can be a sensitive metric of mechanical tissue disruption and therefore a metric of treatment effectiveness. This feedback and monitoring technique allows for early observation of changes as a result of the acoustic cavitation / histodisruption process, allowing for early detection of significant or complete tissue effects (e.g., invasion). Changes in tissue can be identified prior to the onset of tissue erosion (occurrence of erosion). In one embodiment, this method can be used to monitor the acoustic cavitation / tissue destruction process for advanced drug delivery where the treatment site / tissue is disrupted over time and tissue damage / erosion is not desired. In other embodiments, this can include speckle decorrelation due to scattering motion in a progressively fluidized treatment volume, for example, where partial or complete tissue erosion is desired.

[0095]

[0100] For systems that include elastographic feedback and monitoring, and as background information, as the treatment site / tissue is further fragmented (homogenized, fractured, or eroded) by the acoustic cavitation / histotripsy effect, its mechanical properties change from a soft but interconnected solid to a viscous fluid or paste-like state with little long-range interaction. This change in mechanical properties can be measured by various imaging modalities, including MRI and ultrasound imaging systems. For example, ultrasound pulses can be used to induce forces (i.e., radiation pressure) on a localized volume of tissue. This tissue response (displacement, strain, and velocity) can change significantly during histotripsy treatment, allowing the state of histotripsy to be determined by imaging or other quantitative means.

[0096]

[0101] The system may also include feedback and monitoring based on changes in shear wave propagation. As background, tissue fragmentation makes the tissue more fluid and less solid, and fluid systems generally do not propagate shear waves. Therefore, the degree of tissue fluidization provides an opportunity for feedback and monitoring of the histotripsy process. For example, ultrasound and MRI imaging systems can be used to observe shear wave propagation. The disappearance of such waves in the treatment volume is used as a metric for tissue destruction or disruption. In one embodiment of the system, the system and support subsystems can be used to generate and measure interacting shear waves. For example, two adjacent ultrasound foci may perturb the tissue by pushing it in a specific way. If the adjacent foci are in a fluid, no shear waves propagate to interact with each other. If the tissue is not fluidized, the interaction will be detected using external means, for example, by different frequencies that are detected only when two shear waves interact nonlinearly, the disappearance of which correlates with tissue damage. Thus, the system can be configured to use this modality to enhance feedback and monitoring of acoustic cavitation / histotripsy procedures.

[0097]

[0102] For systems that include acoustic emission feedback and monitoring, and as background information, as the tissue volume is fragmented, its impact on acoustic cavitation / tissue disruption (e.g., the bubble cloud in this case) changes. For example, bubbles can grow larger, have different lifetimes, collapse, and change properties in intact versus fluidized tissue. Bubbles can move and interact even after tissue fragmentation, creating larger bubbles or cooperative interactions between bubbles, all of which result in altered acoustic emissions. These emissions can be heard during treatment and change during treatment. Analysis of these changes and their correlation with treatment effectiveness allows for monitoring of treatment progress and can be configured as a system feature.

[0098]

[0103] For systems that include feedback and monitoring via electrical impedance tomography, and as background information, an impedance map of the treatment site can be created based on the spatial electrical properties of the entire treatment site. Electrical measurements of the skin surface can be taken to estimate imaging of the conductivity or permittivity of the patient's treatment site. 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 at the surface, and voltage is measured at multiple points using the electrodes. This process can be repeated for different settings of applied current. The resolution of the resulting image can be adjusted by varying the number of electrodes employed. The impedance map provides a measure of the electrical properties of the treatment site within the skin surface, allowing the system and Depending on the configuration of the system and supporting subsystems, this can be used to monitor the changes and location of acoustic cavitation / histotripsy (eg, specifically the bubble cloud) and the histotripsy process.

[0099]

[0104] The user may further be enabled to select, annotate, mark, highlight, and / or outline various regions of interest or treatment sites (on the image) and defined treatment targets, which can be used to command and instruct the system where to image, test, and / or treat via the system software and user interface and display. In some configurations, the user may use a manual ultrasound probe (e.g., a diagnostic handheld probe) to perform the procedure. In other configurations, the system may use a robotic and / or electromechanical positioning system to perform the procedure as directed and / or automated by the system, or conversely, the system may allow for a combination of manual and automated use.

[0100]

[0105] The system may further include the capability to perform image registration, including imaging and image dataset registration to enable navigation and localization of the system relative to the patient, including the treatment site (e.g., tumor, critical structures, bony anatomy, anatomical structures and their features, etc.). In one embodiment, the system allows a user to image and identify a region of interest, e.g., the liver, using embedded ultrasound and select and mark a tumor (or a surrogate marker) contained within the liver displayed via / in the system software, whereupon the system registers the image data to a coordinate system defined by the system and further enables the system's therapy and robotic subsystems to perform synchronized acoustic cavitation / histotripsy on the marked tumor. The system may further include the capability to register various image sets, including those disclosed above, to one another, as well as provide navigation and localization (e.g., of the therapy transducer on a CT or MRI / ultrasound fusion image by tracking the therapy transducer and robotic subsystem on the image).

[0101]

[0106] The system may also include the ability to operate in a variety of interventional, endoscopic, and surgical environments, including standalone operation and in conjunction with other systems (surgical / laparoscopic towers, vision systems, endoscopic systems and towers, ultrasound-enabled endoscopes, ultrasound (flexible and rigid), percutaneous / endoscopic / laparoscopic, and minimally invasive navigation systems (e.g., optical, electromagnetic, shape-sensing, ultrasound-enabled, etc.), which may also interface with or include various optical imaging capabilities (e.g., fiber and / or digital). The systems of the present disclosure may be configured to interface with these systems, and in some embodiments may be collocated and interface with them, or in other embodiments, all or part of the system (e.g., acoustic cavitation / tissue disruption-enabled endoscopic systems or laparoscopic surgical robots) may be incorporated into the above systems / platforms. In many of these environments, the system may be used during or before or after use of, for example, an optically guided endoscope / bronchoscope, or, as another example, a laparoscopic robot (e.g., Intuitive Digital). Therapy transducers can be used when a Vinch*Xi system is observing / manipulating the tissue / treatment site. These environments and examples can also include when the other systems / platforms described above are used to deliver fluid (locally) to enable the creation of artificial acoustic windows (e.g., transducers placed externally on / around the patient) that may not exist under normal circumstances (e.g., fluidizing a sector or lobe of the lung in preparation for acoustic cavitation / histotripsy via noninvasive transthoracic therapy). The systems disclosed herein can also include all or part of their subsystem hardware packaged within other system carts / consoles / systems described herein (e.g., acoustic cavitation / histotripsy systems and / or subsystems integrated and operated from the navigation or laparoscopic systems described above).

[0102]

[0107] The system can also be configured to display real-time visualization of the bubble cloud in space and time, including the resulting tissue effects during and after treatment due to tissue / bubble cloud interactions, according to various of the above and other parameters, where the system can dynamically image, visualize, and display the bubble cloud and its changes (e.g., decrease and increase in echogenicity), which may include intensity, shape, size, location, morphology, persistence, etc. These capabilities may enable users to continuously track and follow treatments in real time in one integrated procedure and interface / system, allowing for on-the-spot confirmation of treatment safety and efficacy (this is in contrast to other interventional or surgical modalities that either require multiple procedures to accomplish the same or do not allow real-time visibility of treatment effects (e.g., radiation therapy) or where such is not feasible (e.g., real-time visualization of local tissue during thermal ablation), and / or where other procedures require additional invasive procedures (e.g., incision or puncture) and repeated imaging in a scanner (CT or MRI scanning) between treatment steps). The above-disclosed systems, subsystems, components, modalities, mechanisms, and workflows / methods of use may be implemented in an unlimited manner by enabling hardware, software, user interfaces, and environments of use, and future improvements, enhancements, and inventions in this field, along with the resulting data and means of using that data for analytics, artificial intelligence, or digital health applications and systems, are considered to be within the scope of this disclosure.

[0103] robot

[0108] The system may include various robotic subsystems and components, including, but not limited to, one or more robotic arms and controllers, which may further cooperate with other subsystems or components of the system to perform and monitor acoustic cavitation / histotripsy. As described herein above, the robotic arms and control systems may be incorporated into one or more cart configurations.

[0104]

[0109] For example, one embodiment of the system may include a cart with an integrated robotic arm and control system, therapy, integrated imaging and software, where the robotic arm and other listed subsystems are controlled by the user in a single bedside cart form factor.

[0105]

[0110] In other embodiments, the robotic subsystems can be configured in one or more separate carts that can be driven in a master / slave configuration from a separate master or cart, where the robotic-enabled cart is located at the bed / patient side and the master is located at a distance from the cart.

[0106]

[0111] The disclosed robotic arms can be comprised of multiple joints, compartments, and degrees of freedom and may also include a variety of built-in sensor types and encoders implemented for various uses and safety functions. Sensing techniques and data may include, by way of example, vision, potentiometer, position / localization, motion, force, torque, velocity, acceleration, and / or dynamic loading. In some cases, sensors may be used to allow a user to direct robot commands (e.g., hand gestures to place the robot in a preferred setup position or store it in place). Further details regarding robotic arms are described in U.S. Patent Publication No. 2013 / 0255426 to Kassow et al., the entire contents of which are incorporated herein by reference.

[0107]

[0112] The robotic arm receives control signals and commands from a robotic control system that can be housed on the cart and can be configured to provide a variety of functions, including but not limited to position, tracking, patterns, triggers, and events / actions.

[0108]

[0113] The positions may be configured to include fixed positions, pallet positions, time controlled positions, distance controlled positions, variable time controlled positions, and variable distance controlled positions.

[0109]

[0114] The tracking may be configured to include time-controlled tracking and / or distance-controlled tracking.

[0110]

[0115] The pattern of movement may be configured to include intermediate positions or waypoints and a series of positions along a defined path in space.

[0111]

[0116] The trigger may be configured to include distance measurement means, time, and / or various sensor means, including but not limited to those disclosed herein, visual / imaging, force, torque, localization, energy / power feedback, and / or others.

[0112]

[0117] Events / actions may be configured to include a variety of examples, including proximity methods (approaching / moving away from a target), activation or deactivation of various effectors (e.g., therapy transducers), start / stop / pause sequences of the above events, triggering or toggling of events / actions, initiating a pattern of movement, changing / toggling between patterns of movement, and / or time-based or temporal events / actions across defined tasks and space-time.

[0113]

[0118] In one embodiment, the system includes a three-degree-of-freedom robotic positioning system that enables a user (via the system's software and associated user interface) to micro-position the therapeutic transducer in an X, Y, and Z coordinate system, while coarse macro-positioning of the transducer (e.g., aligning the transducer with the patient's body) is performed manually. In some embodiments, the robot may include six degrees of freedom, including X, Y, Z, pitch, roll, and yaw. In other embodiments, the robotic subsystem may include additional degrees of freedom that enable the robotic arm support base to be positioned along a linear axis parallel to the approximate direction of the patient surface and / or the support base's height to be adjusted upward or downward, thereby allowing the position of the robotic arm to be modified 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, etc.

[0114]

[0119] The robotic arm or arms may also include various mechanisms to assist in manual or semi-manual manipulation and correction of arm position, which may interface on or between the therapy transducer and the robotic arm's distal-most joint. In some embodiments, the mechanisms are configured to include one or more handles that allow for manual manipulation and manual control. The handles may also be configured to include user input and electronic control mechanisms for the robotic arm that command various drive functions or modes (e.g., activate or deactivate free-drive modes) to operate the robot to assist in coarse or fine positioning of the arm. Workflows for initial positioning of the robotic arm and therapy head can be configured to first allow the therapy transducer / head to be positioned in the coupling solution, with the therapy transducer directly interfaced to the arm, or, in a different workflow, allow the user to set up the coupling solution first, and then allow the robotic arm to interface with the therapy transducer / coupling solution as a later / final setup step.

[0115]

[0120] In some embodiments, the robotic arms can include laparoscopic, single-port, endoscopic, hybrid or combination thereof, and / or other robotic arms, and the robots in the system can be slaves to a master controlling the arms, or in some cases, multiple other arms equipped to perform other tasks in parallel (visualization, 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 can be used to prepare the surgical site, including manipulating organ position to provide better acoustic access and, in some cases, further stabilizing the organ to minimize respiratory motion. In conjunction with this, a second robotic arm can be used to perform noninvasive acoustic cavitation through the body cavity under real-time imaging (e.g., ultrasound) from a therapeutic transducer and simultaneous visualization with a laparoscopic camera. In other related aspects, similar techniques may be used with a combination of endoscopic and non-invasive techniques, as well as a combination of endoscopic, laparoscopic and non-invasive techniques.

[0116] join

[0121] The system may include various coupling subsystem embodiments that are enabled and configured to enable acoustic coupling to the patient (e.g., providing an acoustic medium and its support between the transducer and the patient) to provide effective acoustic cavitation / histotripsy. The coupling subsystem may include different form factors of the coupling subsystem, including open and closed solutions, and several mechanisms that may be configured to enable dynamic control of the acoustic medium (e.g., temperature, dissolved gas concentration, particulate filtration level, sterilization, etc.). Such dynamic control components may be integrated directly into the system (in the cart) or may be externally located but in communication with the system.

[0117]

[0122] The coupling subsystem typically includes, at a minimum, a coupling medium, a reservoir / container for containing the coupling medium, and a support structure. In most embodiments, the coupling medium is water, which may be conditioned (e.g., cooled, degassed, filtered, etc.) before or during treatment. Various conditioning parameters may be employed based on the configuration of the system and its intended use / application.

[0118]

[0123] The reservoir or medium container can be configured and shaped to conform to the patient and to allow the therapy transducer to fit and function within the acoustic medium according to a defined required workspace (the minimum volume of medium in which the therapy transducer can be positioned and / or moved through one or more treatment positions or patterns, at various separations and depths from the patient, etc.), and the reservoir or medium container can also mechanically support loads and load distribution using mechanical and / or electromechanical support structures. The containers can be of various shapes, sizes, curvatures, and dimensions, can be made of various materials (single, multiple, composite, etc.), and can vary throughout. In some embodiments, the containers can include features such as films, coverings, membranes, bellows, etc. that can be inserted and removed and / or assembled therein. The containers can further include various sensors, drainage tubes, lights (e.g., LEDs), markings, lettering, etc.

[0119]

[0124] In one embodiment, the reservoir or medium container houses a sealable frame that interfaces with the reservoir (which subsequently contains the therapy transducer) as a patient interface, and within which a membrane and / or film may be disposed to provide a comfortable means of providing a barrier to the medium (e.g., water) between the patient and the transducer. In other embodiments, the membrane and / or film may include an opening whose edges provide a mechanical seal against the patient while allowing medium communication with the patient (e.g., a direct water interface with the patient). The reservoir or media container superstructure in this embodiment may further provide a proximal portion (eg, top) of the structure that is open or closed (eg, to prevent spillage or to provide additional functionality).

[0120]

[0125] The disclosed membranes can be composed of various elastomers, viscoelastic polymers, thermoplastics, thermoplastic elastomers, thermoset polymers, silicones, urethanes, hard / soft copolymers, block copolymers, random block copolymers, etc. The materials can be hydrophilic, hydrophobic, surface modified, coated, extractable materials, etc., and can also include various additives to enhance performance, appearance, or stability. In some embodiments, the thermoplastic elastomer can be styrene-ethylene-butylene-styrene (SEBS) or other similar strong, soft elastomers.

[0121]

[0126] The above materials can be formed into useful membranes by molding, casting, thermal spraying, ultrasonic spraying, and / or any other process to produce useful embodiments. The membranes can be disposable or reposable / reusable. The membranes can be provided non-sterile, aseptically cleaned, or sterile, and sterilization can include any known method, including but not limited to, ethylene oxide, gamma, electron beam, autoclaving, steam, peroxide, plasma, chemical sterilization, etc. The membranes can further be configured with a molded outer shell to provide mechanical stability during assembly of the coupling subsystem. Various membrane parameters, including thickness, thickness profile, density, and formulation (e.g., polymer molecular weight and copolymer ratio), can be optimized for this use, including optimization to maximize acoustic properties, particularly to minimize cavitation onset threshold and / or impact on ultrasound imaging artifacts, including but not limited to membrane reflections.

[0122]

[0127] Open reservoirs or media vessels may include various filling methods, possibly including the use of pre-conditioned media or water that can be pumped therein according to predetermined specifications for the water (e.g., temperature level and gas saturation, etc.), or may include additional features integrated into the design that allow for filling and draining (e.g., ports, valves, hoses, tubes, fittings, bags, pumps, etc.).

[0123]

[0128] Sealed reservoirs or media containers may include various mechanisms for sealing, including sealing to the proximal / top portion or structure of the reservoir / container in some embodiments, or sealing to mechanisms on the transducer or transducer housing in other embodiments. Some embodiments may also include dynamic features for controlling the amount of fluid in these designs to minimize the possibility of bubbles or turbulence in the fluid and to allow for changes in focal distance to the target area without moving the transducer. Accordingly, built-in mechanisms for fluid communication and control (such as supplying / removing fluid on demand), including the ability to monitor and control various fluid parameters, some of which are disclosed above, may be provided. To provide this functionality, the coupling subsystem, as a whole or in part, may include a fluid regulation system, which may include various electromechanical devices, systems, power, sensing, computing, and control systems, etc. The reservoir may be configured to receive a signal that causes the reservoir to deform or change shape in a specific, controlled manner to allow for adjustment of the target point without moving the transducer.

[0124]

[0129] The combined support system can include a variety of mechanical support devices that interface the reservoir / container and medium with the patient and workspace (e.g., bed). In some embodiments, the support system includes a mechanical arm with three or more degrees of freedom that can interface with one or more features of the bed, including, but not limited to, a frame, rails, customized rails, or inserts, and one or more of the reservoirs or containers. The arm may interface with multiple locations. The arm may be a mechanism mounted on one or more carts, which may be configured in a variety of non-limiting permutations, and in some cases, the cart may only serve to support and provide the support structure disclosed.

[0125]

[0130] In some embodiments, the support structure and arm may be a robotic-enabled arm implemented as a stand-alone cart or incorporated into a cart that further includes two or more subsystems, or the robotic-enabled arm may be the arm of another interventional, surgical, or other type of robot, and may further include various user input mechanisms for actuating / controlling (e.g., positioning in / within the binding medium) the robotic arm and / or binding solution mechanisms (e.g., filling, draining, etc.).

[0126] software

[0131] The system may include various software applications, mechanisms, and components that allow the user to interact with, control, and use the system for many clinical applications. The software may communicate and coordinate with one or more of the subsystems, including, but not limited to, the therapy, integrated imaging, robotic and other components, auxiliary mechanisms, and accessories of the system.

[0127]

[0132] Overall, and in no particular order of importance, the software initializes, sets up, services the system, communicates / imports / exports / stores data, allows the user to change / operate / configure / control / command various settings and parameters, reduces safety and user related hazards, plans treatments, controls various configurations of transducers, robotic arms, and drive systems, function generators and amplifier circuits / slaves, test and treatment ultrasound sequences, steering and positioning of transducers (e.g., electromechanical and electronic beam steering), treatment patterns, imaging and support for imaging probes, their manual and electromechanical / robotic movement, measurement of various dimensions in or around the treatment site (e.g., depth from one anatomical site to another), etc. The system may provide mechanisms and support for imaging support for measurement / characterization, pre-treatment diagnostics and protocols for measurement / characterization of in situ treatment site properties and conditions (e.g., acoustic cavitation / tissue disruption threshold and heterogeneity), target alignment and target registration, calibration, marking / annotation, localization / navigation, alignment, guidance, workflow provision and guidance, autonomous execution of treatment steps, treatment plans and protocols, autonomous execution under direct and visual observation using real-time imaging according to software display including various fields and viewing viewpoints for autonomous and visual observation, communication tools (video, audio, sharing, etc.), troubleshooting, providing instructions, warnings, alarms, and / or providing support for communication via various networking devices and protocols.It is further envisioned that the software user interface and supporting displays may include various buttons, commands, icons, graphics, text, etc. that enable a user to effectively interact with the system in a user-friendly manner, and may be presented in a non-limiting number of permutations, layouts, and designs, may include multiple displays (e.g., a touchscreen monitor and touchpad), and / or may be displayed in a similar or different manner or set of mechanisms for a system that is networkable with one or more external displays or systems (e.g., another robot, a navigation system, a system tower, a console, a monitor, a touch display, a mobile device, a tablet, etc.).

[0128]

[0133] The software may support the various above-mentioned function generators (e.g., FPGAs), amplifiers, power supplies, and treatment transducers as part of a representative system that includes one or more computer processors. / It may be configured to allow the user to select, determine and monitor various parameters and settings for tissue disruption, and upon observing / receiving feedback regarding performance and status, may allow the user to stop / start / change said parameters and settings.

[0129]

[0134] 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 once it is connected to the system (and verification of the appropriate sequence and parameter settings based on the selected application). In other embodiments, the software can update targeting and amplifier settings (e.g., channels) based on the specific transducer selection. The software may also provide transducer recommendations based on pre-treatment and planning inputs. Conversely, the software may provide an error message or warning to the user if the treatment transducer, amplifier, and / or function generator selection or parameters are incorrect, malfunction, or cause injury. This may further include reporting the details and location.

[0130]

[0135] 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 may include any associated patient, procedure, clinical and / or technical data and may be used to inform, modify and / or guide current or future treatments or procedures / interventions, whether as a decision aid (e.g., using serial data sets to construct and guide new treatments) or as an active part of the treatment itself.

[0131]

[0136] As part of planning or during treatment, the software (in conjunction with other components of the system) may enable the user to assess and test acoustic cavitation / histodisruption thresholds at various locations within a user-selected region of interest or a predefined treatment volume to determine a minimum cavitation threshold throughout the region or volume to ensure treatment parameters are optimized to achieve, maintain, and dynamically control acoustic cavitation / histodisruption. In one embodiment, the system allows the user to manually assess and test threshold parameters at various points. These points may include points at the defined boundaries, within the boundaries, and at the center of the region / location of the selected region of interest and treatment volume, with resulting threshold measurements reported / displayed to the user and used to update treatment parameters prior to treatment. In another embodiment, the system may be configured to enable automatic threshold measurements and updates enabled by the robotic subsystem described above, where the user can instruct the robot or the robot can be commanded to perform measurements autonomously.

[0132]

[0137] The software, in conjunction with a computer processor and one or more function generators, amplifiers, and treatment transducers, can be configured to enable various permutations of implementing and positioning optimized acoustic cavitation / histotripsy throughout a selected area / volume, including fixed / natural focus placement using a purely electromechanical positioning arrangement, electronic beam steering (with or without electromechanical positioning), electronic beam steering to a newly selected fixed focus by further electromechanical positioning, axial (Z-axis) electronic beam steering by lateral (X and Y) electromechanical positioning, fast axial electronic beam steering by lateral electromechanical positioning, fast beam steering in 3D space, and adjusting one or more acoustic cavitation / histotripsy parameters based on the above functions to update treatment parameters based on threshold measurements. These may include, but are not limited to, systems configured with various combinations of these, including dynamically changing the amplitude of the beam (e.g., dynamically adjusting the amplitude across the treatment area / volume).

[0133] Other components, auxiliary mechanisms and attachments

[0138] Systems may include various other components, ancillary features and accessories, including, but not limited to, computers, computer processors, power supplies including high voltage power supplies, controllers, cables, connectors, network devices, software applications for integration into security, communications, information systems including hospital information systems, cellular communication devices and modems, handheld wired or wireless controllers, goggles or glasses for advanced visualization, augmented reality or virtual reality applications, cameras, sensors, tablets, smart devices, phones, internet-enabled features on objects, special purpose "apps" or user training materials and applications (software or paper-based), virtual proctors or trainers, and / or other enabling features, devices, systems or applications, and / or methods of using the above.

[0134] System Variations and Methods / Applications

[0139] In addition to performing a wide range of procedures, the system may enable additional benefits such as enhanced planning, imaging, and guidance to assist the user. In one embodiment, the system may enable the user to create patient, target, and application-specific treatment plans, where the system may be configured to optimize treatment parameters based on feedback to the system during planning, and the plan may further include the ability to run various test protocols to gather specific inputs to the system and the plan.

[0135]

[0140] The feedback may include various energy, power, site, position, tissue and / or other parameters.

[0136]

[0141] The system and the above feedback can be further configured and used to autonomously (and robotically) execute optimized treatment plans and protocol implementations visualized under real-time imaging during treatment, thereby allowing the user to directly observe the local treatment tissue effects as treatment progresses and start / stop / modify treatment at the user's discretion. Both the test and treatment protocols can be updated during treatment at the user's discretion or, in some embodiments, based on logic built into the system.

[0137]

[0142] It should also be understood that many of these benefits can further enhance other forms of acoustic therapy, including thermal ablation using high intensity focused ultrasound (HIFU), high intensity therapeutic ultrasound (HITU), including boiling histotripsy (thermal cavitation), and are considered part of this disclosure. The present disclosure also contemplates the application of histotripsy as a means of activating pre-delivered inactive drug payloads that are inactive due to protection in micelles, nanostructures, or similar protective structures, or due to molecular arrangements that allow activation only upon application of acoustic energy.

[0138]

[0143] In another embodiment, a treatment subsystem, including, in part, one or more amplifiers, transducers, and power sources, can be configured to enable multiple acoustic cavitation and histotripsy driving functions and provide specific advantages based on application, method, and / or patient-specific use, including, but not limited to, the ability to deliver more energy with more desirable thermal profiles, faster treatment rates, and shorter procedure times, and to provide greater optimization and control of treatment parameters, which may enable electronic beam steering and / or other functions.

[0139]

[0144] The present disclosure also includes novel systems and concepts related to systems and subsystems, including novel "universal" amplifiers that may enable multiple drive techniques (e.g., single and multi-cycle pulsing), which, in some embodiments, may include various novel features to further protect the system and user with respect to electrical safety or other hazards (e.g., damage to the transducer and / or amplifier circuitry).

[0140]

[0145] In another aspect, the system and treatment subsystems may include multiple treatment transducers, configured for specific applications and uses, capable of treatment across a wide range of operating parameters (e.g., target size, depth, location), and may include a wide range of operating specifications (described in more detail below). The transducers may further be adapted, interfaced, and connected to robotic-enabled systems and coupling subsystems, allowing the transducers to be positioned within or juxtaposed to an acoustic coupling device, thereby enabling simultaneous imaging and histolytic treatment through appropriate acoustic windows in many embodiments. Because the tissue effects and bubble cloud of acoustic cavitation / histolytic treatment may or may not vary in appearance and intensity throughout treatment depending on its location within the treatment (e.g., tumor, surrounding healthy tissue, critical structures, adipose tissue, etc.), the treatment transducers may also include built-in imaging probes or localization sensors that can display and determine the location of the transducer within the treatment site and provide a direct view (or representation) of the treatment site.

[0141]

[0146] The systems, methods, and uses of the systems disclosed herein may be beneficial in overcoming 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 of blood vessels, cardiovascular, pulmonary, and / or neurocranial related spaces, cosmetic / aesthetic, metabolic (e.g., type 2 diabetes), plastic and reconstructive, ophthalmic and ophthalmic, orthopedic, gynecological and andrological, and other systems, devices, and methods for the treatment of diseased, injured, unwanted, or healthy tissue, organs, or cells.

[0142]

[0147] Systems and methods are also provided for improving interstitial treatment patterns that can shorten treatment times, improve efficacy, reduce the amount of energy delivered to the patient, and reduce pre-focused tissue heating.

[0143] Usage environment

[0148] The disclosed systems, methods of use, and system applications can be implemented in many environments and situations, with or without various support systems such as anesthesia, including, but not limited to, procedure rooms, operating rooms, hybrid rooms, inpatient and outpatient facilities, ambulatory facilities, imaging centers, radiography, radiation therapy, oncology, surgery, and / or any medical center and clinic, mobile medical center or system, automobiles and related vehicles (e.g., vans), air and sea transport such as aircraft and ships, and / or any structure capable of providing temporary therapeutic treatment support (e.g., tents). In some cases, the systems and / or subsystems disclosed herein can be provided as integration mechanisms into other environments, such as direct integration of the histotripsy treatment subsystem into an MRI scanner or patient surface / bed, where, at a minimum, the treatment generator and transducer are integrated therein; in other cases, the histotripsy configuration further includes a robotic positioning system, which can also be integrated into the scanner or bed design.

[0144] Multi-approach tissue disruption robotic system and method

[0149] Currently, there are significant unmet needs in interventional and surgical medical procedures, including those using minimally invasive devices and techniques to treat disease and / or injury, and across a variety of procedure types, that could be solved by entirely new medical procedures. Current medical system capabilities are often limited by access, where minimally invasive or non-invasive techniques are preferred, or current means are unable to achieve the desired / necessary tissue effect (e.g., operating around / through critical structures without significant injury), or the physical setup of the system makes certain treatment techniques less desirable or impossible, and combinations of techniques may enable entirely new procedures and techniques not currently possible, along with enhanced tissue effect treatments.

[0145]

[0150] Disclosed herein are robotic systems and methods that can use various combinations of percutaneous / laparoscopic, endoscopic, and / or non-invasive / percutaneous devices controlled by various combinations of manual, semi-manual, and / or automated techniques, both enabled together to enable targeted delivery of tissue disruption and acoustic cavitation, where tissue disruption is one step to enable further steps during surgery / procedure (e.g., treatment of tumors entrapped around critical structures to make an inoperable patient operable via robotic-assisted laparoscopic resection), or conversely, where tissue disruption is the primary "treatment or therapy" objective of the procedure, and other robotic systems of the multi-approach system / method are used for other supporting treatment steps (e.g., visualization, ligation, fluidization, or stabilization of an organ or organ space). This may be possible entirely within a single robotic platform architecture (e.g., a bed-based robot with arms configured for endoscopic and non-invasive procedures), or conversely, it may be performed by multiple separate robotic architectures or systems operating in coordination (e.g., an endoscopic bed-based surgical robot working in conjunction with a cooperative non-invasive tissue disruption cart-based robot).

[0146]

[0151] As a non-limiting representative example illustrating the concepts of the present disclosure, such systems and techniques may be used to enable pancreatic cancer resection, where a bedside non-invasive tissue disruption robotic system can be used to treat tumor-infiltrated vasculature (which would normally make a surgical procedure too risky), and upon completion, a master-slave laparoscopic robot (column-based patient-side cart, e.g., Intuitive Surgical's Da Vinci Xi System) can be used to complete the laparoscopic robotic resection of the pancreas (and associated tumors). Similar techniques can be used using multiple robotic system architectures for other cancer-related surgical procedures, including, but not limited to, liver, kidney, lung, colorectal, and other complex procedures, where more patients would benefit from more access to, downstaging, or in some way assisting in, a better surgical procedure, or enabling more patients who would otherwise be medically unsuitable for surgery and / or enabling more healthcare providers / surgeons to perform such procedures.

[0147] Multi-approach setup and surgical perspective

[0152] Additionally, the disclosed multi-approach tissue disruption robotic system is configurable to allow for various permutations of setup, environment, and surgical perspective (e.g., user orientation relative to the system, robotic arm and patient placement). Such a system also includes the unique feature of having simultaneous combinations of instrument / device access (e.g., ports or trocars, various types of endoscopes, catheter access, etc.), including acoustic access (e.g., devices / methods / materials that enable acoustic coupling for ultrasound visualization and tissue disruption along a planned / desired acoustic path). It is envisioned that there are infinite configurations and combinations of setups and accesses.

[0148] Robot System Architecture

[0153] Regarding robotic system architectures that may incorporate one or more types of the disclosed multi-approach robotic methods, the system architectures may include bed-based, column-based, boom-based, cart-based, imaging bed or gantry-based, and pod-based systems, and / or other envisioned system architectures, as well as combinations thereof. Some embodiments may include multiple sets of systems (e.g., multiple carts), each set enabled with at least one robotic arm. In embodiments using mixed combinations of system architectures (e.g., column- and cart-based), the combinations may be interconnected via various software and / or electrical connections and associated communication protocols (e.g., allowing one system software control or access to system features / parameters on other architecture systems), or may operate cooperatively but independently (without direct electrical, mechanical, and / or software communication connections between them). The use of multiple systems (and architectures) can be configured to be coupled / connected via one or more cables to simplify the environment and avoid clutter. Certain functions may be provided by separate cables and connectors, including other support for power, optics, imaging, ultrasound imaging, hospital information systems, histotripsy, mechanical and robotic control, fluidics, and / or other control. Connectors / cables may be located in various locations on the system, including, but not limited to, side panels, arms, control panels and user interfaces, displays, end effectors, transducers, patient coupling devices, etc.

[0149] Control System and User Interface

[0154] With regard to system control for the robotic / system control system, the system may be configurable to include a console (local to the form factor, e.g., on a patient side cart), user interface, display, touch display, and associated controls (physical and software) integrated with each of the above-mentioned form factors, or may further be configured to include master / slave, control room, and / or other remote configurations that further enable users to control and interact with such systems from remote locations via known communication methods.

[0150] Robotic Arm for Multi-Approach Systems

[0155] The robotic arms of the disclosed systems may include a variety of architectures, arm bases, degrees of freedom, joints, reach, payload, repeatability, and sensing capabilities, including configurations for open, semi-open, laparoscopic, single-port laparoscopic, endoscopic, and natural orifice, percutaneous, and / or non-invasive (e.g., non-invasive) surgery. The disclosed arms are configured to interface with and control a variety of devices, instruments, and tools, and may be further configured to calculate, align, coordinate, and control, and monitor / supervise these arms, in part, through generally known geometries, trajectories, orientations / poses, tool / base coordinates, dimensions, movements, movement patterns and paths, and robotic arm encoders and control data. In some embodiments, robotic arms and system architectures configured for histotripsy procedures allow for configuration in C-arm, fluoroscopy, extended fluoroscopy, and / or cone-beam CT environments to enable x-ray data acquisition (and collision avoidance) during robotic performance of histotripsy.

[0151] System End Effectors, Instrumentation and Tools

[0156] In some embodiments of the system instrumentation and tools used by one or more of the robotic arms of the present disclosure, the instrumentation / tools may include an access device. The tools may include scissors, scissors, graspers, clip appliers, staplers, internal staplers, energy-based devices including radiofrequency, ultrasound, microwave with or without cutting / dissecting and / or cauterizing capabilities, spacers, hemostats, sealants / adhesives, various other electrosurgical and ablation devices, needles, needle drivers, flexible catheter or endoscope-based devices, navigation / positioning devices for guiding rigid or flexible instruments, sensing devices, biopsy devices, or any other tools necessary for the procedure. The instruments and tools can be interfaced with the robotic arm via various interfaces and instrument insertion and drive mechanisms and support architectures.

[0152]

[0157] An instrument driver (e.g., an instrument drive mechanism or instrument device manipulator) may incorporate electromechanical means for actuating a medical instrument / device, as well as a removable / detachable medical instrument that may not include any electromechanical components, such as a motor, allowing the instrument to be sterilized but separate from the system. The driver may include one or more drive units (each drive unit including a separate drive shaft) axially arranged to provide controlled torque to the instrument via a drive shaft for interfacing with the instrument, gearhead, motor, encoder to provide feedback to the control circuit, and control circuitry for receiving control signals and operating the drive units. An instrument may be paired with the driver using a drive input / output to enable coupling via a drive interface that allows coupling of the instrument. In some embodiments, the instrument interface includes an interface designed to electromechanically interface with therapeutic transducers of various configurations and designs (e.g., atraumatic / external body contouring, open, laparoscopic, single-port laparoscopic, endoscopic), which may include an electromechanically coupled imaging transducer, which may be encoded to support probe rotation, as an example.

[0153]

[0158] Instruments may be electronically keyed / coded for automatic recognition by the system, and system software may guide, recommend, and / or recognize various combinations of tools for a given procedure, or conversely, prompt, inform, and / or warn the user if an appropriate combination has not been selected for a given selected procedure. In some embodiments, instruments and tools may be configured to be threaded / exchanged through one another (e.g., a needle-based device through a flexible endoscope actuated by a robotic arm).

[0154]

[0159] The instrument may further include, but is not limited to, any diagnostic, interventional or surgical tools, any additional auxiliary devices / implants, rigid or flexible, that enable treatment or therapy (e.g., fiducial markers, surgical probes, tissue / cell dyes, stains, labels, molecular probes and / or optical elements, etc.).

[0155] Imaging and visualization for multi-approach systems

[0160] In some examples of system visualization and imaging devices, the system may include and / or be configured to operate with various modalities and frameworks, including, by way of example, optical vision systems and optical flow methods, fluorescence, near-infrared, light scattering, elastic scattering spectroscopy, optical coherence tomography, endoscopic confocal microscopy, and various other biophotonics and optical modalities, Raman spectroscopy, etc. The system may be based on, but not limited to, various segmentation, reconstruction, and image processing methods to provide the ability to visualize the patient, treatment technique, device / treatment trajectory, anatomical sites / locations surrounding / intervening and containing the treatment location, critical structures, anatomical sites / locations surrounding / containing the target disease / injury / undesired tissue, dynamic real-time treatment effects, and pre-treatment / intra-treatment / post-treatment treatment verification, etc., in one or more fields of view, all in relation to the position / pose of one or more robotic arms, via one or more user interfaces. The visualization and position data may include, communicate with, or be configured to integrate with, ultrasound, x-ray systems, computed tomography (CT), cone beam CT, enhanced fluoroscopy, magnetic resonance imaging (MRI), photoacoustic imaging, low frequency ultrasound / near infrared imaging platforms (e.g., similar to open water procedures and systems), and various combinations thereof, including specialized image registration, fusion, flow, virtual reality, and augmented reality. In some embodiments, the visualization and position data, when monitored by robotic encoders, may enable automatic image registration at the start of a procedure, or conversely, may enable a return to a previous known position / pose that was time-stamped earlier in the procedure, as needed / desired, and / or in emergency situations.

[0156] A tissue homogenization system that enables multiple approaches

[0161] The multi-approach robotic histotripsy treatment system and its core histotripsy subsystem are configured to shape, sense, enhance, modify, implement, dynamically adjust, and control histotripsy, and can be configured to include and be based on all known methods thereof, including impact scattering, intrinsic thresholds, and any method using single, multiple, and / or partial-cycle histotripsy pulses. Histotripsy treatments can also be used with a specific minimum number of pulses and with a minimum of one bubble cloud of one shape / size at one treatment location to partially or completely destroy tissue, enabling example applications ranging from opening passageways to plaque removal, including immune responses and pathways, marking tissue (e.g., as fiducials), removing entangled structures (e.g., tumors entangled on bile ducts or blood vessels), treating tumors, nerves or nerve centers, treating fine or delicate structures in the eye, and any other treatment where well-controlled histotripsy effects provide significant utility. Histolytic treatments can also be designed to destroy specific tissue types while sparing others, a capability made possible by the differing energy requirements of different tissues, determined by water content, viscoelasticity, and tight bonds, to name a few important factors.

[0157]

[0162] Histotripsy therapy transducers can be configured in small form factors on rigid, semi-flexible, or flexible endoscopic and percutaneous devices, or in some embodiments, may include larger form factors for laparoscopic surgical procedures (<15 mm devices), including wrist or articulated devices, open surgical procedures (e.g., <5 cm usable on a shaft or rod), or in other embodiments, larger (approximately 20 cm or greater) body-contoured configurations designed to deliver histotripsy pulses deep within the body (peritoneal cavity or brain). These can include various geometries and shapes and numbers of individual / single elements supported by drive hardware equipped to support a fixed focus and / or electronic focus steering in one or more directions or axes. Transducers may be linear, convex, or concave. The tissue disruption subsystems described above may be capable of transmitting and / or transmitting and receiving, including various systems / methods for cavitation mapping, and include associated drive hardware incorporated into any robotic system or subsystem approach (e.g., patient side cart / robot versus vision system auxiliary cart housing other core subsystems such as optical visualization, electrosurgical devices, etc.).

[0158] Example of multi-approach robotic histolytic treatment [Example]

[0159]

[0163] 2A and 2B, an embodiment of a multi-approach robotic tissue disruption system and procedure is shown, which includes a surgical system including a tissue disruption system 200 (corresponding to the tissue disruption system 100 described above) and an endoscopic (bronchoscopy) robotic system 202 configured to prepare a treatment site / area for a patient P resting on an operating table 203. It has been done.

[0160]

[0164] The histotripsy system can be configured to enable lung-targeted treatment or treatment of any hollow / hollow organ (such as the colon) via a prepared treatment location. The endoscopic robotic system uses navigation and position / localization sensing capabilities to allow a user, such as a physician or surgeon, to access any desired hollow organ location. For example, in lung treatment, the endoscopic robotic system can access any airway location (and level) within the lung, including one or more suspected target lung elements (or known cancers), at the lobar, segment, or subsegmental level, allowing the user to fluidize the airway to create an acoustic window within the selected level / anatomical location. These specific treatment steps are intended to prepare the location sufficiently to receive acoustic treatment, including histotripsy. Fluidization of the airway may include using a biocompatible medium, including saline, buffered saline, and / or other aqueous media, which may also be configured with acceptable oxygen / gas saturations and degassed as such. The method of fluidization may include navigating to a predetermined location / branch in the airway and, optionally, mechanically blocking / sealing the adjacent location from fluid. The fluidization and / or blocking of the location can be viewed on registered images (e.g., CT scans or optical images) and tracked / monitored in real time by navigation, direct optical visualization, and / or by fluorescence or cone beam CT (with x-ray monitoring).

[0161]

[0165] Depending on the configuration, the endoscopic robotic system may allow the fluidization step to be performed by the imaging system 204 under continuous real-time visualization (e.g., optical camera, catheter ultrasound, etc.) and localization (e.g., electromagnetic navigation, shape sensing, etc.) of the position relative to the segmented airway tree, and under full field of view using enhanced fluoroscopy and cone-beam CT (e.g., visualization of the entire thoracic cavity, CT and body separation, etc.). Depending on the configuration, the visualization mechanism may need to be removed before additional instruments are inserted. Additional devices used through the working channel of the bronchoscopy robot or endoscope, inserted and replaced one or more times, can also be used to perform these steps. This may further include an acoustic coupling medium, such as a balloon catheter or other device usable for delivering degassed water or degassed saline, and for enabling sealing of the fluidized lung compartment (at the lobar, segment, or subsegmental level) with fluid.

[0162]

[0166] Working in concert with the endoscopic / bronchoscopy robotic system, a non-invasive histotripsy robot can be positioned over a target hollow organ location (e.g., over the chest wall for lung treatment) in an orientation and position that aligns the geometric focus of the histotripsy treatment transducer with the user-selected and predefined hollow organ target. The histotripsy robot can then be enabled to deliver histotripsy pulses and treatment through an acoustic window provided via the endoscopic robotic system. In some embodiments and methods, some or all of these steps are performed with the patient positioned on a bed to allow for the acquisition of enhanced fluoroscopy and cone-beam CT data, which are acquired during one or both of the robotic procedures. Enhanced fluoroscopy and cone-beam CT may be used to assist with planning, treatment, and treatment verification. [Example]

[0163]

[0167] In another embodiment similar to Example 1, the bronchoscopy robot comprises a Monarch robot (Auris Helth, JNJ). This particular example provides simultaneous continuous optical imaging, electromagnetic navigation, and working channel access for all fluidics-required procedural steps. In this example, the anatomical location, therapeutic effect (e.g., Radial probe endobronchial ultrasound can be used to visualize tissue disruption (bubble cloud), and tissue effects (changes in tissue reflectance / scattering after treatment). [Example]

[0164]

[0168] In another embodiment similar to Example 1, the bronchoscope robot includes an Ion robot (Intuitive Surgical, Inc.). This particular example provides simultaneous optical imaging and shape-sensing localization, but also requires the camera system to be removed so that the fluid delivery device can be inserted into the working channel for fluidics support devices and related steps (e.g., delivery of degassed water and use of a balloon catheter for sealing the proximal airway). In another related example, this multi-approach can be configured to use the endoscopic robot (Ion) and the tissue disruption bedside cart robot, all in a cone-beam CT environment (non-invasive transcostal approach), where cone-beam CT is used to acquire images for planning, lung preparation and fluidization, navigation, device localization, and visualization of treatment before, during, and after tissue disruption. The cone beam can also be used to calculate transducer pose / position and, based thereon, predict treatment location, and to align ultrasound data with the cone-beam data (and synchronize with the robot arm position encoders). [Example]

[0165]

[0169] In a further embodiment similar to Examples 1-3, in a multi-approach system for pulmonary treatment involving the use of an exemplary robotic system such as Monarch (Auris Health, JNJ) or Ion (Intuitive Surgical, Inc.), the histotripsy robot can be further configured with multi-aperture ultrasound imaging (MAUI) to allow the user to visualize the target and surrounding lung tissue. The MAUI imaging mechanism can be configured as a MAUI imaging probe coaxially mounted to the histotripsy treatment transducer, both mounted at the end of the histotripsy system robotic arm. [Example]

[0166]

[0170] In another embodiment related to Examples 1 through 4, referring to FIG. 3A , a surgical system can include a histotripsy system 300 (corresponding to the histotripsy system 100 described above) and a laparoscopic robot 302 configured to access and prepare a hollow organ (e.g., lung) of a patient P for treatment. As described above, the patient can be placed on a surgical table 303. In a lung treatment embodiment, the laparoscopic robot can be used in a master / slave configuration (e.g., Intuitive Surgical's Da Vinci Xi) to prepare the lung for wedge, subsegmental, segmental, or lobar-level resection. In combination with this, the histotripsy system (patient-side cart with user console) can be configured to treat hollow organs (e.g., associated lung tumors and associated nodules) immediately prior to the laparoscopic procedure. The Da Vinci robot can further be used to fluidize the patient's body cavity adjacent to the target hollow organ (e.g., the thoracic cavity prior to application of histotripsy in the lung) to enable acoustic coupling for histotripsy treatment. As described above, the surgical system can include an imaging system to enable visualization during treatment. In some embodiments, endobronchial ultrasound (EBUS) is used to view the nodule / tumor before / during / after tissue disruption. [Example]

[0167]

[0171] Another embodiment similar to Example 5 is shown in Figure 3B, in which a surgical system can include a tissue disruption system 300 and a laparoscopic robot 302 (and arms) configured to access and operate on a target hollow organ, such as a lung, and further includes a robotic endoscopic system 304 (flexible). The robotic endoscopic system can also access and operate on the hollow organ itself. In this embodiment, if the target hollow organ is the lung, the robotic endoscopic system can be configured to fluidize the lung, which may include the lung itself (whole lung, lobes, or lobules) and / or the thoracic cavity (extrapulmonary) to enable enhanced acoustic coupling for treatment directed into / through the lung. The laparoscopic robot 302 example of FIG. 3B can be configured to laparoscopically access the target hollow organ and further includes the capability to fluidize a patient cavity surrounding or adjacent to the target organ (e.g., the thoracic cavity in the case of pulmonary treatment). Similarly, the endoscopic robot can provide access within the hollow organ itself and include the capability to fluidize the hollow organ. Histolytic treatment may be performed by one of multiple additional robotic arms or a separate bedside cart. In another related example, the surgical system can include any of the imaging systems described above, including ultrasound, CT, fluoroscopy, and multi-aperture ultrasound imaging. [Example]

[0168]

[0172] Another embodiment incorporating the concepts of Example 6 includes a system and method for performing liver-targeted histolytic therapy with significant transcostal acoustic blockage. This embodiment may further include scenarios in which the histolytic therapy transducer can be positioned with full rib coverage (e.g., maximum acoustic blockage from the ribs), and the airways and / or thoracic cavity can be fluidized to further provide a better acoustic window into and through the lungs, enhancing therapy directed toward the abdomen, which may share a similar pathway. In another related embodiment, a robotic arm enabled with a histolytic therapy transducer may include a multi-aperture ultrasound imaging probe configured to visualize the interior of the lung parenchyma and liver. [Example]

[0169]

[0173] In another example, a multi-arm laparoscopic robot in a bed-, column-, or cart-based architecture, including one arm coupled with an endoscope for visualization, is configured to observe the disappearance of a molecular / surgical probe during and / or after treatment with non-invasive (extracorporeal) tissue disruption enabled by a second robotic arm. In one embodiment, the surgical probe is a near-infrared probe, allowing direct fluorescent visualization of labeled tissue / cells (e.g., specifically labeled tumor cells). In another embodiment, the entire system configuration (laparoscopic and non-invasive) provides the ability to visualize the probe, surgical end effector, tissue, and echogenicity and echogenicity changes of the target tissue or bubble cloud under B-mode ultrasound (from the non-invasive arm) simultaneously with the near-infrared probe through the laparoscopic arm's vision system, allowing immediate therapeutic verification of tissue effects by the reappearance of the (disappeared) molecular / surgical probe upon tumor / tissue destruction. [Example]

[0170]

[0174] In another example, referring to FIG. 4 , a robotic system 401 can include many of the features / functionality of the robots described above. In one embodiment, the robotic system can include: 1) one or more robotic arms 402 configured for laparoscopic procedures; 2) one or more robotic arms 403 configured for endoscopic procedures; 3) one or more robotic arms 400 configured for non-invasive (histotripsy) procedures; and 4) one or more manual or robotic arms 404 for patient access / interfacing, including acoustic access / interfacing. Unlike the systems described above with separate endoscopic / laparoscopic / histotripsy robots, this embodiment includes a single robotic system with multiple arms for each subsystem. The robotic system 401 can be configured for various orientations and perspectives, enabling multi-view procedures with minimized arm collisions and enhanced setup and ease of use. Each robotic arm can be controlled from a single master in a master / slave configuration, or different arms (and accompanying robot-enabled tools / end effectors) can be actuated / controlled via multiple user interfaces or consoles. In some embodiments, the robotic system may include a bed-based robotic system. In other embodiments, the robotic system may be configured as a patient-side based robot (e.g., Intuitive Surgical's Da Vinci). The robotic system may be configured with surgical instruments, visualization / imaging probes (e.g., optical, ultrasound), and histolytic treatment transducers, with the primary user interface and control system being a robot master. [Example]

[0171]

[0175] In another example, similar to Example 8, but with each specific tool coupled, actuated, and controlled via a dedicated bedside cart, all carts are remotely connected to one or more user input devices or masters. In some embodiments, the tissue disruption system may be controlled via a dedicated user interface / console. In other embodiments, all robotic arms and devices are controlled by a single master. [Example]

[0172]

[0176] One or more of the possible configurations disclosed herein are configured to be used to treat pancreatic tumors and perform tissue disruption to render early-stage or mid-stage medically inoperable patients operable by enabling better surgical access and treatment of tumor-associated vasculature, including skeletonizing vascularly infiltrating tumors without damaging the vasculature, pancreatic duct, biliary system, or sensitive bile ducts. By doing so, tumors that would normally pose too significant medical patient risk and injury (such as unintended collateral injury due to tissue bleeding perforation) may be rendered operable by allowing better preparation and management of critical structures to minimize potential adverse events.

[0173]

[0177] For example, in one embodiment, a multi-approach robotic system including a laparoscopic / endoscopic / histotripsy system can be configured to convert a medically inoperable patient into a surgical patient. There are many possible reasons why a patient may be medically inoperable, including the inability to access tumor-associated blood vessels or sensitive inter-organ lumens or ducts. In some embodiments, as described above, the target organ (e.g., the pancreas) can be visualized internally or externally by the endoscopic robotic system. Histotripsy treatment can then be applied to a targeted area of ​​the target organ to liquefy or dissolve the soft tissue. Histotripsy can be specifically tailored to target only the soft tissue and not the blood vessels, ducts, lumens, etc. For example, by controlling the histotripsy pulse to achieve cavitation only above a certain threshold, only the targeted soft tissue can be dissolved, leaving the blood vessels, ducts, lumens, etc. undamaged. Upon completion of the histotripsy treatment, the laparoscopic robotic system can be used to operate on the remaining tissue structures (e.g., blood vessels supplying the target tumor, sensitive ducts, lumens, etc.). [Example]

[0174]

[0178] Similar to Example 11, one or more multi-approach tissue disruption robots are used in a multi-approach robot configuration to enable debulking of pancreatic tumors and stroma, resulting in increased tumor perfusion and improved drug delivery. In this example, tissue disruption can be used to disrupt soft tissue and cellular components of the tumor and surrounding stromal components to reduce interstitial and intratumoral pressure. For mechanically more resilient stromal structures and structures, including tumors and adjacent tumor tissue, variable pulse sequences can be used to impart the desired damage / tissue effect. Also, specific bubble cloud patterns and paths (moving the bubble cloud through the pattern) can be varied to deliver specific spatial patterns containing fractional treatments (and / or variable doses therein, e.g., total number of pulses) to control the extent of the tissue effect. Alternatively, an ablation cavity can be created for the local application of chemotherapy and / or immunotherapy agents. [Example]

[0175]

[0179] A multi-approach robot configured to allow the surgeon to directly visualize the pancreas and liver, including through the use of an endoscope, while simultaneously treating non-invasively with histotripsy. In some embodiments, histotripsy treatment is configured to prepare the target organ system for resection, which may include skeletonizing the organ to make resection more amenable (e.g., enhanced vascular and bile duct management) and minimize potential adverse events (e.g., bleeding or pancreatic leakage). In other procedures, histotripsy treatment may be used to divide tissue much like scissors or a scalpel, leaving the ducts intact, for subsequent treatment with commonly used ligation and stapling devices, such as sutures, clips, or energy-based ligation devices, such as bipolar, monopolar, ultrasound, or microwave. [Example]

[0176]

[0180] A multi-approach robot configured with multiple robotic arms for performing tissue-sparing surgery on the kidney, wherein two or more laparoscopic robotic arms are configured and coupled to laparoscopic tools / instruments including visualization, and one or more robotic arms are configured for non-invasive tissue disruption. In some embodiments, the multi-approach robot may be configured with flexible endoscope-compatible robotic arms and drive systems for visualizing the interior of the kidney before, during, or after tissue disruption. In some embodiments, the robotic system may use image guidance, including, but not limited to, ultrasound and ultrasound fusion with CT and / or MRI, with real-time ultrasound imaging registered to position data obtained by the robotic arm encoders.

[0177]

[0181] In another example, for a combined laparoscopic and atraumatic approach, but from a single system, a minimally robotic, three-arm approach may include one arm for laparoscopic visualization of the kidney and workspace, one or more laparoscopic surgical tools, and a tissue disruption transducer. In this embodiment, all devices may be controlled via a single master / console. [Example]

[0178]

[0182] An example includes any of the above-described examples or multi-approach robotic system configurations that can be envisioned, where one of the robotic systems, or multi-robot form factor systems, uses a freehand ultrasound component to assist in planning or directing treatment. Additionally, in some embodiments, the freehand ultrasound device is positionally tracked, possibly with six or more degrees of freedom, and further registered with other ultrasound images or videos, or other imaging modalities (e.g., optical, CT, MRI, etc.). [Example]

[0179]

[0183] A multi-approach system is configured to overcome the current challenges of treating intracerebral hemorrhage or blood clots, using a catheter-based, bed / table-based (integrated with and / or adjacent to the table) robotic drive system in conjunction with a non-invasive transcranial histotripsy system approach (bed / table-side) to liquefy and aspirate the hemorrhage, clot, or thrombus. In another related embodiment, this multi-approach configuration may be implemented within a cone beam CT as a single integrated system approach. [Example]

[0180]

[0184] In some embodiments of Example 16, the catheter-based robot is a Corindus / Siemens robot. In other embodiments, the catheter-based robot may be a Hansen endovascular / neuroendovascular compatible robotic system. Also, in some cases, one or more of the robots (catheter or histotripter) can be remotely operated from a local control room (which also controls the cone beam CT) and / or a remote location (e.g., another cancer center). [Example]

[0181]

[0185] An example of a combination of intraneuronal robotic techniques and non-invasive transcranial histotripsy, where the applications are to treat, remove / aspirate tumor remnants or lysates from the brain, relieve pressure, open anatomical structures (e.g., ventricles), and / or remove aggressive lesions from affected / surrounding areas. Conversely, following the above, the intraneuronal robot may be used to administer treatments, including drugs, immunotherapy, cell therapy, localized radiation, and / or combinations thereof, and return to the previous histotripsy treatment site. [Example]

[0182]

[0186] Examples similar to Examples 16 to 19, but for treatment of meningiomas, subdural hematomas, and epidural hematomas, where the treatment site is subdural or epidural and very shallow. [Example]

[0183]

[0187] In a further embodiment, a catheter-based robot provides navigation and access for delivery of a catheter hydrophone to facilitate minimally invasive localization of the bubble cloud and enable a robotic arm configured with a tissue disruption transducer. This multi-approach system can be further configured as one integrated system or as collaborative robots / methods working in concert. [Example]

[0184]

[0188] A surgical robot configured with a minimum of four robotic arms, including an arm coupled to a visualization device, a tissue manipulator (e.g., a grasper), a clip applier and / or vessel sealing instrument, and a tissue disruption transducer, both enabled for abdominal procedures and visceral tissue resection. In one particular embodiment, the tissue disruption transducer is used to achieve immediate tissue cavitation and skeletonization when sealing of the skeletonized tissue (e.g., liver) is immediately followed by the clip applier / vessel sealing instrument. [Example]

[0185]

[0189] A typical example is where a laparoscopic robot (patient side cart) is used to stabilize and hold the organ / tissue within a fluid-filled endobag or containment device (via a laparoscope), and a non-invasively applied second histotripsy therapy transducer can be used to liquefy / destroy the tissue contained within the endobag or containment device. Alternatively, the second histotripsy therapy transducer may be applied directly to the fluid-filled bag or containment device. [Example]

[0186]

[0190] In one embodiment, a multi-approach robotic procedure for thyroidectomy is performed, where percutaneous surgical instrumentation is used to remove complex / mixed morphology tissue, and a non-invasive histotripsy transducer is actuated by a robotic arm operable to couple / manipulate / direct said histotripsy transducer above the thyroid gland external to the body. The complex / mixed morphology tissue may contain heterogeneous tissue as viewed by ultrasound, and histotripsy is used for direct tissue treatment within a desired / user-defined section within the heterogeneous region, followed by percutaneous surgical instrumentation. The tissue is aspirated / removed by the method. The user can continue / repeat treatment as desired based on real-time feedback on tissue changes. [Example]

[0187]

[0191] In one example, a laparoscopic robot is configured with surgical instrumentation for resection of the prostate gland, and one arm of the robot includes a non-invasive histotripsy transducer for transperineal treatment. In a related but separate embodiment, a transrectal histotripsy transducer is used for the same procedure to enable marginal and circumferential laparoscopic resection and aspiration of unwanted residual tissue remnants.

[0188]

[0192] Further non-limiting examples of whole body and procedure multi-approach tissue disruption robotic systems and methods can be envisioned and are not intended to be limiting. [Example]

[0189]

[0193] In one embodiment, a laparoscopic robot is configured with surgical instrumentation for resection of colorectal tumors, with one arm of the robot including a non-invasive histotripsy transducer for transperineal treatment. In some embodiments, the colon can be fluidized prior to histotripsy to create an acoustic window in the colon. In a related but separate embodiment, a transrectal histotripsy transducer is used for the same procedure and to enable marginal and peripheral laparoscopic resection and aspiration of unwanted residual tissue remnants.

Claims

1. 1. A method of treating tissue of a patient with a robotic surgical system, comprising: identifying a target tissue location with an imaging subsystem of the robotic surgical system; preparing the target tissue location for histolytic treatment with a laparoscopic subsystem of the robotic surgical system; and performing a histotripsy treatment at the prepared target tissue location with a histotripsy subsystem of the robotic surgical system.

2. The method of claim 1 , wherein the imaging subsystem comprises an endoscopic robotic system.

3. The method of claim 1 , wherein the imaging subsystem comprises an ultrasound imaging system.

4. The method of claim 1 , wherein the imaging subsystem comprises a CT imaging system.

5. The method of claim 1 , wherein the imaging subsystem comprises an augmented or enhanced multi-modality imaging system.

6. The method of claim 1 , wherein the imaging subsystem comprises a fluoroscopic imaging system.

7. The method of claim 1 , wherein the imaging subsystem includes an imaging device disposed on a robotic arm of the robotic surgical system.

8. 10. The method of claim 1, wherein preparing the target tissue location further comprises ablating intervening tissue between the patient's exterior surface and the target tissue location.

9. 10. The method of claim 1, wherein the target tissue location comprises a hollow / lumen body organ, duct, or lumen, and the step of preparing the target location further comprises the step of fluidizing the target tissue location with the laparoscopic subsystem to form an acoustic window in the target tissue location and / or in a pathway to the location.

10. 10. The method of claim 1, wherein administering histolytic treatment further comprises dissolving or liquefying the target tissue location.

11. 10. The method of claim 1, wherein the target tissue location includes a first tissue structure and a second tissue structure, and wherein administering a histolytic treatment dissolves or liquefies the first tissue structure but does not dissolve or liquefy the second tissue structure.

12. The method of claim 11 , wherein the first tissue structure comprises soft tissue.

13. 12. The method of claim 11, wherein the first tissue structure comprises cancerous tissue.

14. 12. The method of claim 11, wherein the first tissue structure comprises tumor tissue.

15. The method of claim 11 , wherein the second tissue structure comprises a blood vessel.

16. The method of claim 11 , wherein the second tissue structure comprises a duct, including a bile duct.

17. 10. The method of claim 1, wherein the step of performing histotripsy comprises: assessing a cavitation threshold at one or more locations within the target tissue location; and optimizing histotripsy treatment parameters based on the assessed cavitation threshold.

18. 10. The method of claim 1, wherein the tissue disruption subsystem is disposed on a robotic arm that includes three or more degrees of freedom.

19. The method of claim 1 , wherein the robotic surgical system comprises a cart / column-based surgical system.

20. The method of claim 1 , wherein the robotic surgical system comprises a bed-based surgical system.

21. 1. A surgical system comprising: at least one imaging subsystem configured to identify a target tissue location in the patient; a laparoscopic subsystem disposed on at least one robotic arm of the surgical system, the laparoscopic subsystem configured to prepare the target tissue location for histolytic treatment; a histotripsy subsystem disposed on at least one robotic arm of the surgical system, the histotripsy subsystem configured to administer histotripsy treatment to the prepared target tissue location.

22. 22. The system of claim 21, wherein the imaging subsystem comprises an endoscopic robotic system.

23. 22. The system of claim 21, wherein the imaging subsystem comprises an ultrasound imaging system.

24. 22. The system of claim 21, wherein the imaging subsystem comprises a CT imaging system.

25. 22. The system of claim 21, wherein the imaging subsystem comprises an augmented or enhanced multi-modality imaging system.

26. 22. The system of claim 21, wherein the imaging subsystem comprises a fluoroscopic imaging system.

27. 1. A method of treating tissue of a patient with a robotic surgical system, comprising: identifying a target tissue location with an imaging subsystem of the robotic surgical system; preparing the target tissue location for surgery with a tissue disruption subsystem of the robotic surgical system; and performing surgery at the prepared target tissue location with a laparoscopic subsystem of the robotic surgical system.

28. 28. The method of claim 27, wherein the imaging subsystem comprises an endoscopic and / or laparoscopic robotic system.

29. 28. The method of claim 27, wherein the imaging subsystem includes ultrasound imaging.

30. 28. The method of claim 27, wherein the imaging subsystem comprises a CT imaging system.

31. 28. The method of claim 27, wherein the imaging subsystem includes an imaging device disposed on a robotic arm of the robotic surgical system.

32. 28. The method of claim 27, wherein preparing the target tissue location further comprises skeletonizing soft tissue within the target tissue location with the histotripsy subsystem.

33. 28. The method of claim 27, wherein preparing the target tissue location for surgery with the histotripsy subsystem comprises: assessing a cavitation threshold at one or more locations within the target tissue location; optimizing histotripsy treatment parameters based on the assessed cavitation threshold; and administering the histotripsy treatment to dissolve or liquefy only a first tissue structure at the target tissue location and not to dissolve or liquefy a second tissue structure at the target tissue location.

34. 34. The method of claim 33, wherein the first tissue structure comprises soft tissue.

35. 34. The method of claim 33, wherein the first tissue structure comprises cancerous tissue.

36. 34. The method of claim 33, wherein the first tissue structure comprises tumor tissue.

37. 34. The method of claim 33, wherein the second tissue structure comprises a blood vessel.

38. 34. The method of claim 33, wherein the second tissue comprises a duct, including a bile duct.

39. 28. The method of claim 27, wherein the histotripsy subsystem is disposed on a robotic arm that includes three or more degrees of freedom.

40. 28. The method of claim 27, wherein the robotic surgical system comprises a cart / column-based surgical system.

41. 28. The method of claim 27, wherein the robotic surgical system comprises a bed-based surgical system.

42. 28. The method of claim 27, wherein performing the surgical procedure further comprises resecting one or more tissues at the target tissue location with the laparoscopic subsystem.

43. 43. The method of claim 42, wherein the ablating step further comprises using an energy-based cutting, sealing, and / or ligating device, using a monopolar or bipolar device, internal stapling, and / or internal clipping.

44. 28. The method of claim 27, wherein the target tissue location comprises liver, kidney, pancreas, head / neck, thyroid, spleen, prostate, heart, lung, central vasculature, peripheral vasculature, spinal cord and / or brain tissue.

45. 28. The method of claim 27, wherein the surgical procedure further comprises dividing one or more lobes or segments of the liver.

46. 46. ​​The method of claim 45, wherein the divided lobes or segments of the liver are removed from the body.

47. 1. A surgical system comprising: at least one imaging subsystem configured to identify a target tissue location in the patient; a histotripsy subsystem disposed on at least one robotic arm of the surgical system, the histotripsy subsystem configured to prepare the target tissue location for surgery; a laparoscopic subsystem disposed on at least one robotic arm of the surgical system, the laparoscopic subsystem configured to perform a surgical procedure at the prepared target tissue location.

48. 48. The system of claim 47, wherein the imaging subsystem comprises an endoscopic robotic system.

49. 48. The system of claim 47, wherein the imaging subsystem comprises an ultrasound imaging system.

50. 48. The system of claim 47, wherein the imaging subsystem comprises a CT imaging system.

51. 48. The system of claim 47, wherein the imaging subsystem comprises an augmented or enhanced multi-modality imaging system.

52. 48. The system of claim 47, wherein the imaging subsystem comprises a fluoroscopic imaging system.

53. 1. A method of treating tissue with a robotic surgical system, comprising: accessing a target hollow organ location with an endoscopic robotic system of the robotic surgical system; fluidizing the target cavity organ site to form an acoustic window within the target cavity organ site; administering a histotripsy treatment to the fluidized target hollow organ location with a histotripsy subsystem of the robotic surgical system.

54. 54. The method of claim 53, wherein the target hollow organ comprises a lung.

55. 54. The method of claim 53, wherein the target hollow organ comprises the colon.

56. 54. The method of claim 53, wherein fluidizing the target hollow organ location comprises fluidizing the target hollow organ location with the endoscopic robotic system.

57. 54. The method of claim 53, further comprising performing the accessing, fluidizing, and administering steps under real-time imaging guidance.

58. 54. The method of claim 53, wherein the real-time imaging guidance includes CT, fluoroscopy and / or cone beam CT data / imaging.

59. 54. The method of claim 53, wherein the real-time imaging guidance includes ultrasound imaging.

60. 1. A method of treating tissue with a robotic surgical system, comprising: accessing a target hollow organ location with a laparoscopic robotic system of the robotic surgical system; fluidizing a body cavity adjacent the target hollow organ to form an acoustic window to the target hollow organ location; and administering a histotripsy treatment to the target hollow organ location with a histotripsy subsystem of the robotic surgical system.

61. 61. The method of claim 60, wherein the target hollow organ comprises a lung.

62. 61. The method of claim 60, wherein the target hollow organ comprises the colon.

63. 61. The method of claim 60, wherein fluidizing the body cavity comprises fluidizing the body cavity with the laparoscopic robotic system.

64. 61. The method of claim 60, further comprising performing the accessing, fluidizing, and administering steps under real-time imaging guidance.

65. 61. The method of claim 60, wherein the real-time imaging guidance includes CT imaging.

66. 61. The method of claim 60, wherein the real-time imaging guidance includes ultrasound imaging.

67. 61. The method of claim 60, comprising the steps of: fluidizing the target hollow organ location to form an acoustic window within the target hollow organ location; The method further comprising administering a histotripsy treatment within the fluidized target hollow organ location with the histotripsy subsystem.

68. 68. The method of claim 67, wherein the target organ location is visualized in real time using one or more modalities including ultrasound, X-ray based imaging and / or optical imaging.

69. 68. The method of claim 67, wherein the location of the tissue ablation focus is updateable based on feedback provided by real-time imaging guidance.

70. 61. The method of claim 60, wherein the endoscopic / laparoscopic robot uses two or more robotic arms to simultaneously enable real-time imaging guidance, manipulation of one or more surgical instruments / tools, and manipulation of the position of a tissue disruption therapy transducer.

Images