WO2025222034A1

WO2025222034A1 - Histotripsy systems including steerable arrays, and devices and methods thereof

Info

Publication number: WO2025222034A1
Application number: PCT/US2025/025214
Authority: WO
Inventors: Prashant Chopra; David J. Cagle; James Trevor Clark; Ivan H. MA; Roman Devengenzo; Naomi KIBRYA
Original assignee: Petal Surgical Inc
Current assignee: Petal Surgical Inc
Priority date: 2024-04-17
Filing date: 2025-04-17
Publication date: 2025-10-23
Anticipated expiration: 2026-10-17

Abstract

A system includes a histotripsy device including a container configured to contain an interfacing fluid, the container including a surface positionable adjacent to a patient, a treatment device including an array of ultrasound transducers configured to generate pulses of pressure waves that are configured to travel through the interfacing fluid and into tissue to induce boiling histotripsy at a focal volume, and an imaging device configured to capture a view of a target area. The system includes a robotic system including a robotic arm configured to position the histotripsy device such that the surface of the container is adjacent to the skin surface and a positioning device coupled to a distal end of the robotic arm, the positioning device configured to move the treatment device in at least three degrees-of-freedom to cause the focal volume to move throughout the target area to treat the target area using boiling histotripsy.

Description

HISTOTRIPSY SYSTEMS INCLUDING STEERABLE ARRAYS, AND DEVICES AND METHODS THEREOF

Cross-Reference to Related Applications

[0001] This application claims benefit of and priority to U.S. Provisional Patent Application No. 63/635,586, filed April 17, 2024, entitled “APPARATUS AND SYSTEMS FOR BOILING HISTOTRIPSY, AND RELATED COMPONENTS, DEVICES, AND METHODS THEREOF,” and U.S. Provisional Patent Application No. 63/636,544, filed April 19, 2024, entitled “HISTOTRIPSY SYSTEMS INCLUDING STEERABLE ARRAYS, AND DEVICES AND METHODS THEREOF,” the disclosures of which are incorporated herein by reference in their entirety.

Technical Field

[0002] The embodiments described herein relate generally to systems, devices, and methods for treating tissue, including systems, devices, and methods of treating tissue using boiling histotripsy.

Background

[0003] During some procedures, it may be beneficial for surgery to be minimally invasive to reduce the likelihood of bleeding complications and/or infection resulting from the procedure. Once such minimally invasive procedure can include using high-intensity focused ultrasound (HIFU) to cause mechanical and/or thermal effects in tissue, e.g., to disrupt and treat targeted tissue such as a tumor. With boiling histotripsy, bursts or pulses of HIFU can form shock waves or shock fronts that leads to heat deposition through absorption of the shocks. This in turn can lead to the generation of vapor bubbles, which can interact with remaining cycles of the HIFU bursts to leave to tissue fractionation in a targeted region (e.g., a focal region).

[0004] Boiling histotripsy can be employed as noninvasive treatment for malignant tumors, benign prostatic hyperplasia (BPH), deep vein thrombosis, and congenital heart defects. Boiling histotripsy treatments can cause mechanical disruption of tissue with well-demarcated regions of mechanically fractionated treatment volumes that have little remaining cellular integrity. For certain medical applications, tissue fractionation may be more favorable than thermal damage because it produces liquefied volumes that can be more easily removed or absorbed by the body than thermally coagulated solid volumes.

[0005] Existing histotripsy processes and devices are not configured to be efficient in a clinical setting, as the process may be too slow or may not be configured to effectively treat larger target area (e.g., such as a larger tumor volume) or to reduce the number of treatments, increasing workload for a clinician and discomfort for a patient. Thus, there is a need for systems, devices, and methods of performing boiling histotripsy that is more efficient and supports clinicians to reduce workload for the clinician.

Summary

[0006] In some embodiments, a system includes a histotripsy device. The histotripsy device includes a container configured to contain an interfacing fluid. The container includes a surface positionable adjacent to a skin surface of a patient. The histotripsy device includes a treatment device. The treatment device includes an array of ultrasound transducers configured to generate pulses of pressure waves that are configured to travel through the interfacing fluid and into tissue below the skin surface to induce boiling histotripsy at a focal volume. The histotripsy device includes an imaging device configured to capture a view of a three-dimensional (3D) target area of the patient. The system includes a robotic system. The robotic system includes a robotic arm configured to position the histotripsy device near the patient such that the surface of the container is adjacent to the skin surface. The robotic system includes a positioning device coupled to a distal end of the robotic arm. The positioning device is configured to move the treatment device in at least three degrees-of-freedom (DOFs) to cause the focal volume to move throughout the 3D target area to treat the 3D target area using boiling histotripsy.

[0007] In some embodiments, an apparatus includes a support structure. The apparatus includes a container configured to contain an interfacing fluid. The container includes a rigid housing, and a compliant housing coupled to the rigid housing. The rigid housing is configured to be attached to the support structure. The complaint housing is configured to be disposed adjacent to a skin surface of a patient and to deform according to a shape of the skin surface. The apparatus includes a treatment device coupled to the support structure via a positioning device configured to move the treatment device in at least three degrees-of-freedom (DOFs). The treatment device includes an array of ultrasound transducers configured to be disposed in the interfacing fluid, the array of ultrasound transducers is configured to generate pulses of pressure waves that are configured to travel through the interfacing fluid and into tissue below the skin surface to induce boiling histotripsy at a focal volume. The apparatus includes an imaging device coupled to the support structure. The imaging device is configured to capture a view of a three-dimensional (3D) target area of the patient that includes the focal volume.

Brief Description of the Drawings

[0008] FIG. 1 schematically depicts a HIFU system configured to induce boiling histotripsy, according to embodiments.

[0009] FIG. 2A schematically depicts a controller of a HIFU system, according to embodiments.

[0010] FIG. 2B schematically depicts a histotripsy device of a HIFU system, according to embodiments.

[0011] FIG. 2C schematically depicts a robotic system of a HIFU system, according to embodiments.

[0012] FIG. 3A schematically depicts a configuration of a histotripsy device, operating to effect mechanical and/or thermal changes in tissue, according to embodiments.

[0013] FIG. 3B depicts a graph showing a HIFU voltage pulse, according to embodiments.

[0014] FIG. 3C schematically depicts the mechanical and/or thermal changes in tissue, in response to application of HIFU, according to embodiments.

[0015] FIGS. 4A-4B schematically depicts a robotic system configured to position a histotripsy device of a HIFU system, according to embodiments.

[0016] FIG. 5 depicts a flowchart of a method for positioning a histotripsy device for delivering treatment, according to embodiments.

[0017] FIGS. 6A-6D depict a HIFU system including a robotic system, according to embodiments.

[0018] FIG. 7 depicts a HIFU system disposed adjacent to a patient for treatment, according to embodiments.

[0019] FIGS. 8A-10I depict various views and configurations of a portion of a robotic system of a HIFU system, according to embodiments.

[0020] FIGS. 11A-11B depict various views of a reservoir, according to embodiments. FIG.

11C depicts the reservoir of FIGS. 11 A-l IB coupling with a robotic system. [0021] FIG. 12 depicts a fluid flow path of a HIFU system, according to embodiments.

[0022] FIGS. 13A-13B depict a portion of an example robotic system of a HIFU system having three translational degrees of freedom, according to embodiments.

[0023] FIGS. 14A-14L depict various views and configurations of a portion an example robotic system of a HIFU system having a delta robot, according to embodiments.

[0024] FIGS. 15A-16F depict various configurations of robotic systems, according to embodiments.

[0025] FIG. 17 depicts fluid channels of a transducer device, according to an embodiment.

[0026] FIG. 18-19 depicts various views of a transducer focusing element, according to embodiments.

[0027] FIGS. 20-22 depict a transducer coupled to a transducer focusing element, according to embodiments.

[0028] FIGS. 23-25 depict circular treatment patterns, according to embodiments.

[0029] FIGS. 26-27 depict a treatment visualization setup, according to embodiments.

[0030] FIG. 28 depicts a visualization of a lesion formed during treatment, according to an embodiment.

[0031] FIG. 29 depicts a treatment visualization setup including a needle, according to an embodiment.

[0032] FIGS. 30-31 depict visualizations of a needle and a lesion during treatment, according to an embodiment.

[0033] FIG. 32 depicts a boxplot of lesion measurements, according to an embodiment.

[0034] FIG. 33-35 depict visualization of lesion processing, according to embodiments.

[0035] FIG. 36 depicts a tank fixture setup, according to an embodiment.

[0036] FIG. 37 depicts an automated image capture system, according to an embodiment.

[0037] FIG. 38 depicts various views of a needle guide sleeve, according to embodiments.

[0038] FIGS. 39-40 depict various exploded views of a mount for an ultrasound device, according to embodiments.

[0039] FIGS. 41-47 generally depict forming an anatomical model of a spine, according to embodiments. [0040] FIGS. 48-57 depict images of an output of an app for operating, simulating, and visualizing a transducer device.

[0041] FIG. 58 depicts a representation of normalized pressure over a cross-section of tissue, according to an embodiment.

[0042] FIG. 59 depicts a visualization of peak positive pressure, according to an embodiment.

[0043] FIGS. 60-65 depict various views and embodiments of a mechanism for coupling a transducer device to a transducer interface, according to embodiments.

[0044] FIGS. 66-89 depict various example histotripsy devices and/or components thereof, according to embodiments.

[0045] FIGS. 90-93 depict various examples of displays of a histotripsy simulation, according to embodiments.

[0046] FIG. 94 depicts a histotripsy device, according to an embodiment.

[0047] FIGS. 95-96 depict access windows of a line of sight tool, according to an embodiment.

[0048] Optional components and/or elements in the figures are shown in dashed lines, and described as such in the paragraphs that follow.

Detailed Description

I. Overview of Systems and Devices

[0049] The embodiments described herein relate generally to systems, devices, and methods for treating tissue of a patient using HIFU to induce boiling histotripsy. Boiling histotripsy is a minimally invasive procedure that can be applied to tissue to liquefy the tissue in the treatment area. The liquified tissue can be absorbed by surrounding tissue, passed out by the body, or can be removed for analysis (e.g., biopsy, etc.). In some embodiments, a robotic system can be used for positioning a histotripsy device to target a treatment area (e.g., target area, anatomical region of interest, etc.). In some embodiments, the robotic system may move along a predefined treatment path to treat a larger treatment area. In some embodiments, various parameters of a HIFU waveform (e.g., duty cycle, pulse repetition rate, amplitude, frequency, etc.) and/or movement of a HIFU transducer array can be adjusted during treatment, e.g., by a controller and/or robotic system. [0050] In some embodiments, the systems, devices, and methods described herein support preoperative and/or intra-operative clinical decisions and/or treatment planning. For example, to support clinical decisions, systems, devices, and methods described herein can be configured to update or modify a treatment plan based on extraction of treated tissue and/or intra-operative imaging (e.g., using imaging ultrasound). In some embodiments, the treatment plan can be updated as a procedure continues, thus increasing the effectiveness of the procedure. In some embodiments, the system, devices, and methods described herein can include visualizations and/or interfaces for communicating information to medical professionals to aid in clinical decision making.

[0051] In some embodiments, an imaging and tracking system can be used to track the components of a histotripsy system relative to each other and to patient anatomy. This may allow for live treatment planning by a medical professional. For example, the medical professional can be configured to adjust the operation of a robotic device during HIFU treatment, to adjust HIFU waveform parameters, to pause treatment, to adjust the placement or location of one or more components of the HIFU system, among other things. In some embodiments, the systems, devices, and methods described herein can be used to analyze a treatment site and determine whether one or more nearby anatomical structures (e.g., nerves) may need to be moved for a procedure to proceed safely. For example, in spine procedures, systems, devices, and methods described herein can image around a treatment site and determine whether one or more nerves may need to be moved to facilitate treatment of the treatment site. In some embodiments, systems, devices, and methods described herein can provide percutaneous tools or instruments for moving patient anatomical structure, such as a nerve. While certain embodiments described herein are described with reference to specific anatomical regions of interest or specific treatments, the devices, systems, and methods described herein can configured for use with other procedures and treatments.

[0052] FIG. 1 schematically depicts a HIFU or histotripsy system 100, according to embodiments. The system 100 is configured to apply HIFU to induce boiling histotripsy in tissue. The histotripsy system 100 includes a histotripsy device 120, a generator 130, and a controller 150. In some embodiments, the histotripsy system 100 optionally includes a robotic system 110, an imaging device 140, and one or more third-party devices 160. Any combination of the generator 130, the histotripsy device 120, the imaging device 140, the robotic system 110, and/or the controller 150 can be parts of a single device or a plurality of devices.

[0053] In embodiments, the histotripsy system 100 can be configured to treat herniated discs in the spine. In embodiments, the histotripsy system 100 can be configured to treat fibroids, e.g., in the breast, uterine wall, or other anatomy, and/or undesirable tissue growth. In embodiments, the histotripsy system 100 can be configured to treat endometriosis. The generator 130 is configured to generate and supply energy to the histotripsy device 120. In some embodiments, the generator 130 is configured to generate a pulse waveform. The generator 130 may include its own power source (e.g., battery, batteries, etc.) or receive power from an external power source (e.g., grid power, clinic power, generator, etc.). In some embodiments, the generator 130 may include one or more inputs (e.g., button, switch, dial, etc.) for adjusting the energy (e.g., pulse waveforms) generated by the generator 130. In some embodiments, the generator 130 can be a function generator such as, for example, an Agilent 33250A function generator. In some embodiments, the generator 130 can include electrical components that are configured to store energy. For example, the generator 130 can include capacitors that are configured to store energy from a power supply. The generator 130 can be operatively coupled to the controller 150 and the histotripsy device 120 and receive signals from one or both of the controller 150 and the histotripsy device 120. In some embodiments, the generator 130 may deliver a pulse waveform to the histotripsy device in response to receiving a signal indicating that delivering energy to the histotripsy device 120 is desired. In some embodiments, the generator 130 may include one or more electrical components (e.g., electrical conduit, electrical port, etc.) that allows the histotripsy device to operably couple to the generator 130. In some embodiments, the generator 130 is configured to deliver voltage waveforms to the histotripsy device 120 such that the histotripsy device 120 has an output power of between about 300 Watts and about 4,000 Watts, including all sub-ranges and values therebetween.

[0054] The histotripsy device 120 is configured to convert the energy generated by the generator 130 into focused ultrasonic waves for histotripsy. For example, the histotripsy device 120 can be configured to receive a pulse waveform from the generator 130, and to generate a pulsatile wavefront of ultrasound radiation. In embodiments, the histotripsy device 120 can include a transducer array, having a plurality of transducers that can generate HIFU waves. The HIFU waves can be configured to converge at a focal point or focal volume, e.g., to generate a lesion. The focal volume can be located in a target area selected for treatment. In some embodiments, the focal volume can be a three-dimensional volume. Focusing the ultrasound allows for the HIFU waves to deliver enough energy to the target area to allow for boiling histotripsy. Boiling histotripsy includes the heating and formation of bubbles in tissue. In particular, pulsatile wavefronts generated by HIFU transducers can be configured to produce vapor bubbles at a focal volume by heating up the tissue, and to interact with those bubbles to produce cavitation or mechanical fractionation of the bubbles. [0055] The histotripsy device 120 can be positioned by a physician and/or by the robotic system 110. In some embodiments, during treatment, the position of the histotripsy device 120 can be adjusted or moved by the robotic system 110, as further described below. In some embodiments, the histotripsy device 120 can include at least one input. For example, the histotripsy device 120 can include an activation button that, when actuated, can generate a signal to activate the generator 130 and/or activate delivery of a pulse waveform to the histotripsy device 120. In some embodiments, the histotripsy device 120 can be coupled to a robotic system 110, and the robotic system 110 can be configured to signal the generator 130 to deliver pulse waveforms to the histotripsy device 120 during operation.

[0056] The system 100 can be configured to implement a pulsing protocol that takes into account various parameters including ultrasound frequency, pulse repetition frequency (PRF), pulse length, duty cycle, pressure amplitude, etc. For example, the histotripsy device 120 can be configured to have an output frequency of between about 1 MHz and about 3 MHz, including all sub-ranges and values therebetween, and an output power of between about 300 Watts and about 4,000 Watts, including all sub-ranges and values therebetween. The histotripsy device 120 can generate a pulsatile wavefront that includes a plurality of waves formed into a HIFU pulse. In some embodiments, each HIFU pulse has a pulse duration of between about 1 and about 30 milliseconds, including all sub-ranges and values therebetween. The system 100, via control of the generator 130, can be configured to produce the pulsatile wavefront for the pulse duration, followed by a pause, before initiating a subsequent pulse, thereby producing the HIFU pulses at a set PRF. In some embodiments, the PRF of the HIFU pulses can be about 1Hz to about 10Hz, including all sub-ranges and values therebetween. In some embodiments, the ultrasonic waves can be configured to have a pressure amplitude received at the treatment focus or focal volume of greater than about 60 MPa. The waves may be configured to have a negative peak pressure received at the treatment focus of between about 10 MPa and about 15 MPa, including all sub-ranges and values therebetween.

[0057] In some embodiments, the pulsing protocol associated with the HIFU treatment can be adjusted, e.g., based on monitoring of tissue and/or signals associated with the HIFU treatment. For example, the power output, the PRF, the duty cycle, etc. can be adjusted by adjusting the output from the generator 130. In some embodiments, the histotripsy device 120 can include one or more sensor(s) for measuring characteristics of the histotripsy device 120 (e.g., power output, energy usage, orientation, etc.). In some embodiments, the one or more sensors can be configured to measure characteristic of the tissue (e.g., temperature, size of lesion, shape of lesion, etc.). In some embodiments, the histotripsy device 120 can include or be coupled to an imaging transducer (e.g., of an imaging device 140). The imaging transducers can be configured to image the target area to allow for monitoring and/or visualization of the target area. The histotripsy device 120 is described in further detail in reference to FIG. 2B.

[0058] The robotic system 110 is configured to robotically position the histotripsy device 120 relative to a patient such that the ultrasonic waves generated by the histotripsy device 120 are directed toward the target area. In some embodiments, the robotic system 110 is communicatively coupled to the controller 150, which may be configured to command the operation of the robotic system 110. For example, the controller 150 may command the robotic system 110 to orient and/or move the histotripsy device 120 relative to the patient anatomy to generate one or more lesions. The robotic system 110 may include at least one arm and/or at least one joint that can translate and/or rotate the histotripsy device 120 along or about at least one axis. In some embodiments, the robotic system 110 can be operated by an operator (e.g., medical professional, surgical professional, ultrasound technician, etc.) or can be operated automatically by the controller 150. The robotic system 110 is described in further detail in reference to FIG. 2C.

[0059] In some embodiments, the system 100 can include an imaging device 140. In some embodiments, the imaging device 140 is configured to capture image data of a patient’s anatomy and/or other devices nearby, prior to and/or during a HIFU treatment. For example, the imaging device can obtain pre-operative image data of an anatomical region of interest, obtain an intraoperative view of the anatomical region of interest, track the position of an intra-operative device (e.g., robotic system 110, histotripsy device 120, surgical device, etc.), and/or the like. In some embodiments, the histotripsy system 100 can include more than one imaging device 140. For example, the histotripsy system 100 can include an imaging device 140 for obtaining pre-operative image data, an ultrasound imaging device 140 for obtaining an intra-operative view, and/or an imaging device 140 for tracking the position of the intra-operative devices. In some embodiments, the imaging device 140 is statically positioned (e.g., focused on the target area, focused on an operating room, focused on the robotic system 110, etc.). In some embodiments, the imaging device 140 may be repositionable manually (e.g., by an operator) or by a robotic system (similar to the robotic system 110). In some embodiments, the imaging device 140 is communicab ly and/or operably coupled to controller 150. The imaging device 140 may be configured to receive commands from the controller 150 and/or to send image data to the controller 150. In some embodiments, the image data sent to the controller 150 can be used by the controller 150 to monitor temperature of the treated tissue, the boiling activity of the treated tissue, and/or other characteristics of the treated tissue. In some embodiments, the image data sent to the controller 150 can be used by the controller 150 to register pre-operative image data with intra-operative views of the treatment region. In some embodiments, the image data sent to the controller 150 can be used by the controller 150 to track one or more instruments, components, etc. in a working space.

[0060] The controller 150 is configured to control the operation of and/or communicate with the generator 130, the histotripsy device 120, the robotic system 110, and/or the imaging device 140. In some embodiments, the controller 150 is configured to process and/or analyze data received form the generator 130, the robotic system 110, and/or the imaging device 140. The controller 150 can be configured to modify the ultrasonic waves emitted by the histotripsy device 120, e.g., by modifying the power, voltage, pulse parameters, etc. of the generator 130. For example, the controller 150 can operate the generator 130 and the histotripsy device 120 at a predetermined duty cycle. Additionally, or alternatively, the controller 150 may determine a treatment path and operate the robotic system 110 to position/orient the histotripsy device 120 to deliver treatment along the treatment path. In some embodiments, the controller 150 is configured to receive imaging data from the imaging device 140. In some embodiments, the controller 150 can generate a visualization of the position of at least one of the robotic system 110, the histotripsy device 120, and/or the anatomy of the patient based on the image data received form the imaging device 140. In some embodiments, the controller 150 can generate recommendations for a physician, e.g., based on data received from the imaging device and/or other sensors. For example, the controller 150 can recommend if a procedure is safe to proceed, e.g., based on characteristics of the tissue, nearby tissue structures, location of the focal volume relative to the target tissue, etc. Additionally, or alternatively, the controller 150 can determine whether an object and/or anatomy needs to be moved, such that the focal volume of the transducer array and/or nearby anatomical parts (e.g., a nerve). In some embodiments, the controller 150 can provide guidance on the type of tool or tool tip that can be used to move a nerve near the target area. In some embodiments, the controller 150 can be situated nearby the other components of the system 100, such as, for example, a local computer, laptop, mobile device, tablet, etc. In some embodiments, the controller 150 can be remotely situated, such as a server or workstation that is remote from the other components of the histotripsy system 100. The controller 150 is further described with reference to FIG. 2A.

[0061] In some embodiments, the controller 150 can optionally be configured to communicate with third-party devices 160 via a network 102. The network 102 can include one or more network that may be any type of network (e.g., a local area network (LAN), a wide area network (WAN), a virtual network, a telecommunications network) implemented as a wired network and/or wireless network (e.g., Wi-Fi, Bluetooth®, Bluetooth® low energy, Zigbee, etc.) and used to operatively couple to any compute device (e.g., the controller 150). For example, the controller 150 can be configured to send information and/or receive information from one or more third-party devices 160.

[0062] The third-party devices 160 can include user devices (e.g., computer, mobile device, etc.), physician devices, databases, servers, etc. that are configured to communicate with the controller 150. In some embodiments, the third-party devices 160 can send instructions and/or commands to the controller 150. For example, the third-party devices 160 can send treatment plans and/or other information about a patient to the controller 150, which can cause the controller 150 to control one or more of the generator 130, robotic system 110, and/or histotripsy device 120 to follow a certain treatment path and/or to deliver HIFU with a predefined set of parameters (e.g., duty cycle, amplitude, intensity, etc.).

[0063] In some embodiments, the third-party devices 160 can receive information from the controller 150 or components coupled thereto. For example, the third-party device 160 can receive sensor measurements, positions and/or orientations of the robotic system 110 and the histotripsy device 120, and/or imaging data from the controller 150, the generator 130, the robotic system 110, the histotripsy device 120, and/or the imaging device 140. In some embodiments, the third- party devices 160 can be configured to receive and store the information for later reference, e.g., by a physician or other user. In some embodiments, the third-party devices 160 can be configured to generate, using information received from the controller 150, reports, visual representations, and/or other information for presentation to a user. In some embodiments, the third-party devices 160 can be configured to present such information to a user, e.g., via a user interface for communicating information associated with the operation of the histotripsy system 100. In some embodiments, the third-party devices 160 can display prompts for user input. The third-party devices 160 can then send the user inputs to the controller 150, which can be used to control one or more of the generator 130, robotic system 110, and/or histotripsy device 120.

[0064] In some embodiments, the system 100 can include one or more elements from systems and devices described in International Patent Application No. PCT/US2022/081891, titled “System and method for tissue intervention via image-guided boiling histotripsy,” filed December 16, 2022 and/or International Patent Application No. PCT/US2024/061541, titled “Systems, Devices, and Methods for Analyzing and Presenting Physiological Information,” filed December 20, 2024, the disclosures of which are incorporated herein by reference. [0065] FIG. 2A schematically depicts a controller 250 (e.g., structurally and/or functionally similar to the controller 150 of FIG. 1), according to embodiments. The controller 250 can be configured to process and/or analyze data (e.g., from other components of a HIFU system, such as, for example, system 100), present information, and/or generate commands and instructions.

[0066] The controller 250 can include a processor 252, a memory 254, an input/output device 256, and a communication interface 258 (or a multiplicity of such components). The memory 254 can be, for example, a random access memory (RAM), a memory buffer, a hard drive, a database, an erasable programmable read-only memory (EPROM), an electrically erasable read-only memory (EEPROM), a read-only memory (ROM), and/or so forth. In some embodiments, the memory 254 stores instructions that cause processor 252 to execute modules, processes, and/or functions associated with processing and/or analyzing data, presenting information, and generating commands and instructions for the other components of the histotripsy system. In some embodiments, the memory 254 can be configured to store information regarding patients, histotripsy procedures, etc.

[0067] The processor 252 can be any suitable processing device configured to run and/or execute functions associated with the operation of a HIFU system. These functions can include a transducer array movement control 254a, a waveform generator 254b, and a robotic arm control 254c. In some embodiments, the processor 252 may be configured to execute only a subset of the aforementioned functions.

[0068] The processor 252 executing transducer array movement control 254a can be configured to move (e.g., translate, rotate, etc.) a transducer array of a histotripsy device, such as the histotripsy device 120 of FIG. 1, according to a predetermined treatment path or trajectory, e.g., to mechanically fractionate a larger volume of tissue. The processor 252 can be configured to receive a predetermined treatment path as an input, e.g., from a user. For example, a physician may indicate a particular treatment path, e.g., via an input device, and the processor 252 can be configured to control the movement of the transducer array according to the treatment path. Alternatively, or additionally, the processor 252 may be configured to determine a treatment path (or portions thereof) based on information received about a patient (e.g., treatment volume, patient history, etc.).

[0069] When the treatment area is greater than a predetermined size, it may be desirable for the histotripsy device to mechanically fractionate the treatment area by following a treatment path. For example, the treatment path can include moving the focal volume of the histotripsy device to different locations according to a predetermined pattern. In some embodiments, the treatment area may be a three-dimensional volume, and the treatment path may include delivering treatment (e.g., mechanically fractionating the tissue) in layers. In such embodiments, the treatment path can include delivering treatment from the deepest portion of the treatment area (e.g., the portion furthest from the transducer array or most distal) to the shallowest portion of the treatment area (e.g., the portion closest to the transducer array or most proximal). This path can reduce the effect of aberrations and/or changes in tissue structure (e.g., due to mechanical fractionation) in a more proximal area or section from affecting the HIFU waves as they target more distal areas or sections. It can also be desirable to control movement of the transducer array such that the focal volume of the HIFU waves does not induce undesirable heat build-up in one or more tissue portions. For example, the processor 252 can be configured to move the focal volume of the HIFU waves to apply boiling histotripsy to a plurality of tissue portions such that no one portion has an accumulated thermal dose or temperature that is greater than a predetermined threshold. In some embodiments, the processor 252 can be configured to move the focal volume of the HIFU waves according to a treatment path that enables previously treated portions to cool before receiving treatment again. This can help avoid undesirable thermal effects in the treated tissue portions. In some embodiments, the processor 252 can also be configured to pause the application of HIFU waves, e.g., to allow for heat induced by the HIFU waves to dissipate in one or more portions. In some embodiments, the processor 252 executing transducer array movement control 254a can be configured to generate instructions and/or commands that, when sent to the robotic system (e.g., robotic system 110), cause the robotic system to move the histotripsy device to change the focus of the HIFU treatment according to the treatment path.

[0070] In some embodiments, the processor 252 executing transducer array movement control 254a can be configured to determine or modify a treatment path for a target area, e.g., based on image data or other sensor data. For example, during a HIFU treatment, one or more imaging devices or sensors may monitor the progress of the HIFU treatment and/or other tissue characteristics, such as MRI data reflective of tissue contrast changes, temperature data, etc. Based on such information, the processor 252 may determine to continue moving a histotripsy device (e.g., a transducer array) according to a predetermined treatment path or to modify the treatment path. For example, the processor 252 may be configured to modify the treatment path such that the HIFU waves are directed at different tissue portions based on imaging or sensor data that reflects those tissue portions that have been mechanically fractionated and those that require additional HIFU application. [0071] The processor 252 executing waveform generator 254b can be configured to control the parameters of the generated HIFU waves. For example, the processor 252 can be configured to control a generator (e.g., generator 130) to generate pulse waveforms according to set parameters, which in turn can drive a transducer array to produce ultrasound waves having desirable properties. The various parameters can include, for example, power, power density, intensity, oscillation frequency, pulse duration, PRF, duty cycle, and a number of pulses. In some embodiments, the processor 252 can be configured to receive waveform parameters from a user, e.g., via an input device. Alternatively, or additionally, the processor 252 can be configured to determine and/or modify one or more waveform parameters based on information received regarding a patient (e.g., treatment volume, patient history) and/or imaging or sensor data collected regarding a treatment area. In some embodiments, modifying the output can include modifying the power, power density, intensity, oscillation frequency, pulse duration, PRF, duty cycle, and number of pulses. In some embodiments, the processor 252 can be configured to determine the waveform parameters based on the treatment path or trajectory indicated for treating a tissue volume, and vice versa. For example, when the treatment path for applying the HIFU waves involves treating across multiple tissue portions of a larger region or volume, the processor 252 can be configured to control the transducer array to move its focal volume across the multiple portions according to a predefined protocol (e.g., at a predefined rate) while controlling the generator to deliver ultrasound pulses at an increased duty cycle and/or PRF. Such can enable faster treatment time for the entire volume, while avoiding thermal build-up in any one tissue portion that exceeds an upper threshold. In other words, for any one tissue portion, the processor 252 can be configured to control the delivery of HIFU waves to deliver doses of HIFU energy with sufficient time separation between doses to allow induced heat to dissipate and remain within desirable ranges.

[0072] The processor 252 executing the robotic arm control 254c can be configured to move the transducer array (and/or a structure supporting the transducer array) into a desired position engaging or adjacent to the patient. In some embodiments, the processor 252 can be configured to operate a robotic arm of a robotic system (e.g., structurally and/or functionally similar to the robotic system 110 of FIG. 1) to move the transducer array to a desired position. In some embodiments, the processor 252 may operate the robotic arm based on inputs from a user. In some embodiments, the processor 252 can be configured to move the robotic arm automatically and/or semi-automatically to position the transducer array in a desired position. In some embodiments, the processor 252 can be configured to move the robotic arm such that one or more ultrasound transfer media (e.g., fluid, gel, oil, etc.) is configured to interface between the patient to allow for desirable delivery of HIFU energy from the transducer array to the patient. In some embodiments, the processor 252 may first execute the robotic arm control 254c prior to executing the transducer array movement control 254a so that the transducer array is in a desirable position at the patient prior to moving the transducer array for treatment. Additional functionalities of the processor 252 are described in International Patent Application No. PCT7US2024/061541, as described above. [0073] As noted above, the controller 250 can include one or more input/output device(s) 256. The input/output device 256 of the controller 250 can include a display, audio device, or other output device for presenting information to a user. For example, the output device can be configured to present (e.g., via a user interface) the subject’s data and/or reports or output data associated with the procedure. Additionally, or alternatively, the output device can be configured to present (e.g., via a user interface) information showing recommendation and/or prompts associated with the procedure. In some embodiments, the input/output device 256 can include or be operatively coupled to a touchscreen, a keyboard, or other input device or receiving information from a user. The input/output device 256 can be configured to integrate one or more of user instructions, modifications to operation of the histotripsy device, treatment plan, component positioning, and/or the like. The input/output device 256 can allow for the user to select an option on the controller, the option, for example, indicating if a procedure should continue, be modified, and/or be paused or terminated. In some embodiments, the input/output device 256 can display a visualization of at least a portion of the procedure, procedure progress, and/or the like.

[0074] The communications interface 258 of the controller 250 can be configured to receive information and/or send information to other components of a histotripsy system. The communications interface 258 can be a wired or wireless communications interface. As described with reference to FIG. 1, the controller 250 can be configured to communicate via a network with one or more third-party devices. This can be facilitated via the communications interface 258.

[0075] FIG. 2B schematically depicts a histotripsy device 220 (e.g., functionally and/or structurally similar to the histotripsy device 120 of FIG. 1), according to embodiments. As schematically illustrated, the histotripsy device 220 can be configured to engage with a patient P. The histotripsy device 220 includes, optionally, sensor(s) 222, optionally, an imaging transducer 224, a treatment transducer array 226, and an interface 228. In some embodiments, the histotripsy device 220 may be coupled to a robotic system (e.g., structurally and/or functionally similar to the robotic system 110 of FIG. 1) and/or a generator (e.g., structurally and/or functionally similar to the generator 130 of FIG. 1). [0076] The sensor(s) 222 may include one or more sensors configured to measure a characteristic of at least one of the histotripsy device 220 or the patient P. For example, the sensor(s) 222 can include at least one temperature sensor for determining the temperature of a portion of the patient P’s anatomy and/or a temperature sensor for determining the temperature of the transducer array 226. The sensor(s) 222 can include a position and/or an orientation sensor that can measure the movement of the histotripsy device 220 and/or determine its focal volume. In some embodiments, the sensor(s) 222 can include sensors that can measure the output of the histotripsy device 220 (e.g., of the transducer array 226) and/or the input energy received by the histotripsy device 220 from the generator.

[0077] The imaging transducer 224 may be configured to allow for a user to monitor the treatment area while the histotripsy device 220 is in operation. In some embodiments, the imaging transducer 224 is an ultrasound imaging transducer. The imaging transducer 224 may be generally concentric with the transducer array 226 or may be located offset from the transducer array 226. In some embodiments, the histotripsy device 220 may include more than one imaging transducer 224 to capture multiple views of the treatment area. For example, one imaging transducer 224 may be concentric with the transducer array 226 and another imaging transducer 224 may provide a perspective view of the target area.

[0078] The treatment transducer array 226 is an array of transducers configured to deliver HIFU to the patient P. In some embodiments, the transducer array 226 is configured to induce boiling histotripsy at a target area. The transducer array 226 may include a plurality of transducers, each configured to deliver a portion of a total HIFU output. The transducer array 226 is configured such that the ultrasonic waves from the transducers are focused on a focal volume to create a pulsatile wavefront of ultrasound radiation directed at the focal volume. For example, the transducers of the transducer array 226 may be arranged so that waves generated by each transducer converge at the focal volume. This allows the transducer array 226 to be focused on a target area, or a portion of the target area. In some embodiments, the transducers of the transducer array 226 can be arranged in a ring or circle, e.g., with the transducers disposed around the ring. In some embodiments, the transducer array 226 can be arranged in an arch. The shape of the transducer array 226 may be configured for a specific usage. In some embodiments, the transducer array 226 may be configured to allow for certain transducers to be selectively turned off to alter the output of the histotripsy device 220.

[0079] The interface 228 is configured to provide an interface between the transducer array 226 and the patient P that allows HIFU waves to travel into the patient P without much distortion, so that HIFU can effectively be applied to the patient P. The interface 228 can be a tank, bladder, container, reservoir, bag, and/or the like of an interfacing fluid. In some embodiments, the fluid is deionized water, degassed water, and/or the like. In some embodiments, the interface 228 includes a gasket that is configured to form a seal with the patient P. In some embodiments, a partial vacuum can be drawn in the interface to allow for a seal between the interface and the patient P. In some embodiments, the volume of fluid within the interface 228 (e.g., fluid within a bladder) can be increased or decreased (e.g., via removal or leakage, or refilling) for allowing adjustments to the position and/or orientation of the transducer array 226. In some embodiments, the transducer array 226 may be disposed within a portion of the interface and at least partially immersed in the interfacing fluid. In some embodiments, fluid can be circulated into and out of the interface 228 to control the temperature of the fluid within the interface 228. In some embodiments, the interface 228 can be configured to slide or move along the skin of the patient P, e.g., to enable movement of the focal volume of the transducer array 226. For example, the interface 228 can be made of a low friction material that can slide along the body of the patient P. Alternatively, or additionally, the interface 228 can be covered with a fluid or lubricant that allows for the interface 228 to slide/move along the surface of the patient P. In some embodiments, the fluid or lubricant can include an ultrasound gel, castor oil, and/or the like. In some embodiments, castor oil may be desirable as it has a low vapor pressure and therefore is resistant to bubble formation. Castor oil or other low vapor pressure fluids can reduce or minimize bubble formation in the fluid high and low pressure waves pass through the fluid. In some embodiments, a portion of the interface 228 is flexible to allow for the interface 228 to conform to patient anatomy, e.g., to conform to an abdomen of a user, a breast of a user, a chest of the user, etc. For example, the interface 228 can include a flexible membrane configured to contour to the surface of the patient P for improved engagement with the tissue. The improved engagement can enable more efficient and/or effective transmission of pressure waves generated by the histotripsy device into the patient, to thereby treat a target area.

[0080] FIG. 2C schematically depicts a robotic system (e.g., structurally and/or functionally similar to the robotic system 110 of FIG. 1, according to embodiments. The robotic system 210 includes a processor 212, a memory 214, a macro positioning device 216, and a micro positioning device 218. The robotic system 210 can be a component of the histotripsy system, for example, the histotripsy system 100 of FIG. 1. In some embodiments, the robotic system 210 is coupled to at least one of a histotripsy device (e.g., structurally and/or functionally similar to the histotripsy device 120 of FIG. 1 and/or the histotripsy device 220 of FIG. 2B) and/or an imaging device (e.g., structurally and/or functionally similar to the imaging device 140 of FIG. 1). The robotic system 210 can be configured to reposition and/or reorient the histotripsy device and/or the imaging device to engage the treatment area.

[0081] The memory 214 can be, for example, a random access memory (RAM), a memory buffer, a hard drive, a database, an erasable programmable read-only memory (EPROM), an electrically erasable read-only memory (EEPROM), a read-only memory (ROM), and/or so forth. In some embodiments, the memory 214 stores instructions that cause processor 212 to execute modules, processes, and/or functions associated with operation of the robotic system 210. In some embodiments, the memory 214 stores information associated with a treatment path and/or a histotripsy device, such as the histotripsy device 120 of FIG. 1 and/or the histotripsy device 220 of FIG. 2B. In some embodiments, memory 214 can store information in a user profile. For example, the user profile can include information regarding multiple procedures associated with a user. In some embodiments, the memory 214 can store information regarding the position and/or orientation of the robotic system 210. In some embodiments, the memory 214 can store information regarding the position and/or orientation of the patient.

[0082] The processor 252 can be any suitable processing device configured to run and/or execute functions associated with the operation of a robotic system 210. The processor 252 can be configured to execute instructions related to moving the histotripsy device (or treatment transducer array of the histotripsy device) based on a treatment path to apply treatment to a treatment area. For example, the instructions can include instructions for how and when the system 210 should be manipulated based on the treatment plan. In some embodiments, the robotic system 210 may receive instructions. In some embodiments, the robotic system 210 may receive a treatment path and the processor 212 can generate instructions for operating the robotic system 210 according to the treatment path.

[0083] Referring generally to the macro positioning device 216 and the micro positioning device 218, the robotic system 210 is configured to reposition and/or reorient the histotripsy device and/or the imaging device coupled to the robotic system 210. The macro positioning device 216 is configured to position the histotripsy device so that the histotripsy device engages the patient. In some embodiments, the macro positioning device 216 is a robotic arm. In some embodiments, the macro positioning device 216 is a robotic arm formed of one or more sections, each coupled at a joint that couples the sections and allows for at least one degree of motion. In some embodiments, the joins and/or sections can be configured to translate, rotate, and/or the like.

[0084] The micro positioning device 218 is coupled to a distal end of the macro positioning device 216. At least a portion of the histotripsy device is coupled to the end of the micro positioning device 218. For example, the transducer array and/or the imaging system can be coupled to the distal end of the micro positioning device 218. The micro positioning device 218 is configured to position the histotripsy device and, thus, the focal volume. The micro positioning device 218 can be configured to position an imaging transducer to engage the patient. In some embodiments, the micro positioning device 218 can include one or more joints each configured to allow for at least one degree of motion. In some embodiments, the joints can include any number and/or combination of revolute (e.g., rotatory) and/or prismatic (e.g., linear) joints. The micro positioning device 218 is configured to move the focal volume along the target area while delivering treatment. Additionally, the micro positioning device 218 can be configured to move the imaging transducer during treatment so that the imagine transducer can desirably image the target area during treatment.

[0085] FIG. 3A depicts a histotripsy device implemented as a transducer device 320 (e.g., functionally and/or structurally similar to the histotripsy device 120 of FIG. 1 and/or the histotripsy device 220 of FIG. 2B) operatively engaging tissue T of the patient P, according to embodiments. The transducer device 320 includes one or more imaging transducers 324a and 324b (e.g., structurally and/or functionally similar to the imaging transducer 224 of FIG. 2B), a transducer array 326 (e.g., functionally and/or structurally similar to the treatment transducer array 226 of FIG. 2B), and an interface 328 (e.g., functionally and/or structurally similar to the interface 228 of FIG. 2B). The imaging transducers 324a and 324b are shown in dashed lined to indicate that each can be optional. For example, the device 320 can include a single imaging transducer 324a, or a single imaging transducer 324b, or neither of the imaging transducers 324a or 324b. In the latter case, a separate imaging device (not shown in FIG. 3 A) may be used with the transducer device 320, e.g., to capture intraoperative images of the patient P. In embodiments, the interface 328 of the transducer device 320 can be engaged with the patient P, and a medium M can be disposed between the interface 328 and the patient P. The engagement medium M can be an ultrasound gel or a similar substance that reduces friction between the transducer device 320 and the patient P.

[0086] The transducer array 326 of the transducer device 320 can be configured to generate lesions in tissue at one or more focal points or focal volumes F. The focal point F may be the precise point or volume where waves produced by the transducer array 326 converge. During operation of the transducer device 320, the transducer device 320 can be positioned and/or oriented relative to the patient body such that the focal point F is located within a target tissue area T. Further, during operation, the focal point F can be moved (e.g., via movement of the transducer device 320 and/or the patient P) according to a treatment path to deliver energy to multiple portions within the treatment area of the tissue T, e.g., so that treatment can be delivered to the entire treatment area. Operating a transducer device to move a focal point can is further described with respect to the figures below.

[0087] The imaging transducer 324a is optionally concentrically located with the transducer array 326. The imagine transducer 324a can provide a top-down view of the tissue T during operation of the transducer device 320. The imaging transducer 324b is optionally located separate from the transducer device 320 to generate a different view (e.g., a side view) of the tissue T. In some embodiments, the transducer device 320 includes neither, one of, or both the transducer 324a and the transducer 324b.

[0088] The interface 328 can be configured to engage with a tissue surface of the patient P, so that treatment can be effectively applied to the tissue T. The interface 328 can include a medium (e.g., fluid, gel, gas, etc.) that allows for the ultrasonic waves from the transducer array 326 to travel to the tissue T without an undesirable (e.g., less than a threshold) amount of energy lost and/or distortions in the waves. The interface 328 can be configured to be sealed to the patient P (e.g., via suction and/or a seal/gasket) or may be moveable along the patient P. In some embodiments, the interface 328 is configured to selectively seal to the patient P. For example, the interface 328 may be configured to seal to a first position on the patient P, then be removed, then be resealed on a different position of the patient P. In some embodiments, the interface 328 can be flexible to allow for the transducer device 320 to be reoriented or repositioned, e.g., by deforming the interface 328. In some embodiments, the size of the interface 328 can also be changed, e.g., by filling and/or removing fluid from the interface. In an embodiment, the interface is a bladder that can be filled with a fluid.

[0089] FIG. 3B depicts a graph showing a HIFU voltage pulse waveform, which can be used to drive a transducer array to generate HIFU waves, according to embodiments. The graph shows HIFU pulses, which occur for a time period t. The duty cycle of HIFU treatment is defined as the time period t divided by a total time T, which may be the time from the beginning of a pulse to the beginning of a second pulse. The frequency of the HIFU pulses defines the PRF. Each pulse is composed of a HIFU wave that oscillates at an oscillation frequency of greater than 1 MHz and less than 3 MHz, including all sub-ranges and values therebetween. A transducer array (e.g., of a histotripsy device), in response to receiving the pulse waveform, can generate ultrasonic waves having an acoustic pressure of between about 10 MPa and about 15 MPa, including all sub-ranges and values therebetween. The voltage, the frequency, the duty cycle, and/or the PRF can be modified to alter the output of the transducer. [0090] FIG. 3C schematically depicts ultrasound energy E being delivered to tissue, according to embodiments. The ultrasound energy E may be produced by a histotripsy device (or a transducer array thereof), such as any of the histotripsy devices described herein. The ultrasound energy E can be delivered to tissue T of a patient at a focal point or focal volume F. At the focal point F, the ultrasound energy E heats the tissue such that the tissue forms a bubble. Further interactions between the ultrasonic waves and the bubble can cause mechanical fractionation or cavitation. The tissue T at the focal point F is atomized and/or destroyed by the fractionation or cavitation of the bubble. In particular, cavitation at the bubble can result in an acoustic fountain at the focal point F. The ultrasound energy can be delivered in a manner that reduces non-linear heating affects, such that the effects on the tissue are predominantly mechanical.

[0091] FIGS. 4A-4B schematically depict a robotic system 410 (e.g., functionally and/or structurally similar to the robotic system 110 of FIG. 1 and/or the robotic system 210 of FIG. 2C) positioning a histotripsy device 420 (e.g., functionally and/or structurally similar to the histotripsy device 120 of FIG. 1, the histotripsy device 220 of FIG. 2B, and/or the histotripsy device 320 of FIG. 3 A) of a HIFU system, according to embodiments. As seen in FIG. 4A, the robotic system 410 includes a positioning arm 416 (e.g., functionally and/or structurally similar to the macro positioning device 216 of FIG. 2C), a transducer array positioning device 418 (e.g., functionally and/or structurally similar to the micro positioning device 218 of FIG. 2C), and, optionally, an imaging array positioning device 419 (e.g., functionally and/or structurally similar to the micro positioning device 218 of FIG. 2C).

[0092] The positioning arm 416 is coupled to the transducer array positioning device 418 and/or the imaging array positioning device 419 (collectively referred to as the “positioning devices 418, 419”). The transducer array positioning device 418 and/or the imaging array positioning device 419 are coupled to the histotripsy device 420. The positioning arm 416 is configured to position the positioning devices 418, 419 and, thus, the histotripsy device 420, at a location that is proximate to or adjacent to the patient P. For example, the positioning arm 416 may be configured to operate between a disengaged (e.g., storage, transport, etc.) configuration, in which the histotripsy device 420 is positioned away from the patient P, and an engaged configuration where the histotripsy device 420 engages the patient P (e.g., via an interface). In some embodiments, the positioning arm 416 may be a robotic arm with at least three degrees of freedom that is configured to position and orient the histotripsy device 420 in a desired location (e.g., adjacent to the treatment area) on the patient P. For example, the positioning arm 416 can be configured to position the histotripsy device 420 and orient the history device 420 so that treatment can be delivered to a target area for treatment and such that a focal volume of the histotripsy device 420 is adjacent to the target area.

[0093] The transducer array positioning device 418 is configured to position or move a transducer array (e.g., functionally and/or structurally similar to the treatment transducer array 226 of FIG. 2B and/or the transducer array 326 of FIG. 3A) such that the focal volume can be moved throughout the target area, e.g., to induce boiling histotripsy at multiple focal volumes that collectively enable treatment of the entire target area. In some embodiments, the transducer array positioning device 418 is configured to move the histotripsy device 420 in at least three degrees- of-freedom (DOFs) to cause the focal volume to move through a three-dimensional target area. In some embodiments, the transducer array positioning device 418 can be configured to rotate the transducer array.

[0094] As seen in FIG. 4B, the transducer array positioning device 418 can include a plurality of positioners including a first positioner 418a, a second positioner 418b, and a third positioner 418c. The positioners 418a, 418b, 418c can include one or more joints that enable movement of the transducer array in one DOF. For example, the first positioner 418a is configured to allow the transducer to move along a first DOF. In some embodiments, the first positioner 418a can be a revolute joint (e.g., rotary joint, rotary actuator, etc.) or a prismatic joint (e.g., linear actuator, prismatic actuator, etc.). The second positioner 418b is configured to allow the transducer to move along a second DOF, different form the first DOF. In some embodiments, the second positioner 418b can be a revolute joint (e.g., rotary joint, rotary actuator, etc.) or a prismatic joint (e.g., linear actuator, prismatic actuator, etc.). The third positioner 418c is configured to allow the transducer to move along a third DOF, different from the second DOF and the first DOF. In some embodiments, the third positioner 418c can be a revolute joint (e.g., rotary joint, rotary actuator, etc.) or a prismatic joint (e.g., linear actuator, prismatic actuator, etc.). The positioners allow for the focal volume of the histotripsy device 420 to be moved throughout a three-dimensional target area to treat the three-dimensional target area using boiling histotripsy. In some embodiments, the positioners can include motors, actuators (e.g., rotary actuator, prismatic actuator, etc.), and/or the like to move the histotripsy device 420. In some embodiments, the positioners can include arms of a delta robot. In some embodiments, such as when the positioners are in a delta robot, the positioners can include a rotary motor that is configured to rotate an input of a rotary-to -linear transmission to cause translation of a proximal end of the respective positioner and, thus, of the histotripsy device 420. In some embodiments, the first positioner 418a, the second positioner 418b, and the third positioner 418c can be any combination of revolute joints and/or prismatic joints. For 1 example, all can be prismatic joints. In some embodiments, the transducer array positioning device 418 can include any number of additional positioners, e.g., one more, two more, or three more additional positioners or joints. For example, the transducer array positioning device 418 can include additional positioners for rotating, translating, and/or orienting the transducer array.

[0095] As shown in FIG. 4A, the imaging array positioning device 419 is configured to position an imaging transducer (e.g., functionally and/or structurally similar to the imaging transducer 224 of FIG. 2B) of the histotripsy device 420 so that the imaging transducer operatively engages the patient P. For example, the imaging array positioning device 419 can be configured to translate and/or rotate the imaging array positioning device 419 so that it engages the patient P to produce a desired image of the target area. In some embodiments, the imaging array positioning device 419 can include one or more sensors (e.g., strain gauge, force-deflection sensors, elastic sensors, etc.) configured to determine one or more forces between the imaging transducer and the patient P. For example, the one or more sensors can be configured to measure pressure between the imaging transducer and the patient P. In some embodiments, the outputs of the sensors can be used to determine if the imaging transducer is in a safe operating range against the patient P. In some embodiments, the imaging transducer as well as the one or more sensors can be used to determine bubbles in determine locations of bubbles in acoustic coupling fluid and to move the imaging transducer relative to the patient P to move the bubbles to an edge of a desired area. Specifically, the output of the imaging transducer can be used to determine if there are bubbles and the output of the one or more sensors can be used to determine the position of the imaging transducer (e.g., if the imaging transducer is engaging the patient P). The transducer array positioning device 418 and/or the imaging array positioning device 419 can then be actuated to move the imaging transducer to move the bubbles to the edge. In some embodiments, the positioning devices 418, 419 are at least partially disposed within an interface (e.g., functionally and/or structurally similar to the interface 228 of FIG. 2B). For example, the positioning devices 418, 419 may be configured to operate within a fluid inside the interface.

[0096] FIG. 5 depicts a flowchart for a method 500 of positioning a histotripsy device (e.g., functionally and/or structurally similar to the histotripsy device 120 of FIG. 1 and/or any of the histotripsy devices described herein) for delivering treatment, according to embodiments. In some embodiments, the method 500 can be executed by a system such as the system 100 of FIG. 1 and/or any of the systems described herein. The method 500 can be used to deliver HIFU treatment to a target area of a patient. The method 500 can be executed in a hospital setting, a clinical setting, and/or the like. [0097] At 502, the method 500 includes a positioning a histotripsy device, using a positioning arm (e.g., functionally and/or structurally similar to the macro positioning device 216 of FIG. 2C and/or the positioning arm 416 of FIG. 4A-4B) operatively coupled to the histotripsy device, to engage a patient. For example, after a patient is positioned in a desired position, such as on a table, chair, and/or the like, the histotripsy device can be positioned such that it engages a desired area (e.g., adjacent to the treatment area) of the patient. In some embodiments, once the histotripsy device is positioned to engage the patient, an imaging transducer positioning device (e.g., functionally and/or structurally similar to the transducer array positioning device 419 of FIG. 4A) can be configured to operatively engage the patient with an imaging transducer to image the treatment region (e.g., target area).

[0098] At 504, the method 500 includes operating a transducer array positioning device (e.g., functionally and/or structurally similar to the micro positioning device 218 of FIG. 2C and/or the transducer array positioning device of FIGS. 4A-4B) along at least three degrees of freedom to position a transducer array of the histotripsy device to set a focal volume of the transducer array within a treatment region of the patient. In some embodiments, the positioning of the focal volume is based on the output of the imaging transducer. In some embodiments, the transducer array positioning device is configured to move and/or rotate the transducer array along additional degrees of freedom. For example, the transducer array can be rotated, reoriented, and/or the like. In some embodiments, 504 can be executed manually, automatically, or semi-automatically. At 506, the method 500 includes delivering energy to the treatment region via the transducer array. In some embodiments, the method 500 executes 506 once 504 is completed. In some embodiments, energy delivery can be activated manually by a user. The energy is delivered by a generator (e.g., functionally and/or structurally similar to the generator 130 of FIG. 1) as a waveform to the transducer array. The transducer array delivers the energy to the focal volume for treatment using boiling histotripsy.

[0099] At 508, the method 500 includes operating the transducer array positioning device such that the focal volume moves along the treatment region to treat the entire treatment region. In some embodiments, the focal volume can be moved along a predetermined treatment path. In some embodiments, the treatment path can include two-dimensional layers. When delivering treatment in layers, the transducer array positioning device can operate in two degrees of freedom along a layer, then along a third degree of freedom to move to the next layer where the treatment is again delivered along the two degrees of freedom. In some embodiments, if the treatment region is greater than the range (e.g., maximum coverage) of the transducer array positioning device, the positioning arm can be used to reposition the histotripsy device during operation and/or between stages of operation.

[00100] At 510, the method optionally includes, in response to the entire treatment region being treated, terminating waveform delivery to the transducer array. For example, waveform delivery can be terminated after the transducer array positioning device completes a treatment path. In some embodiments, the waveform delivery can be terminated in response to an output of the imaging device indicating that the treatment region has been treated. In some embodiments, waveform delivery can be terminated in response to an anomaly being detected and/or sensed. In some embodiments, waveform delivery can be terminated in response to a user command.

[00101] FIGS. 6A-6D depict a HIFU system 600 (e.g., structurally and/or functionally similar to the system 100 of FIG. 1 and/or any of the systems described herein) with a robotic system 610 (e.g., structurally and/or functionally similar to the robotic system 100 of FIG. 1 and/or any of the robotic systems described herein), according to embodiments. The system 600 includes a cart 605, the robotic system 610 including a positioning arm 616 (e.g., functionally and/or structurally similar to the macro positioning device 216 of FIG. 2C and/or the positioning arm 416 of FIGS. 4A-4B and/or any of the positioning arms described herein) and a transducer array positioning device 618 (e.g., functionally and/or structurally similar to the micro positioning device 218 of FIG. 2C and/or the transducer array positioning device 418 of FIGS. 4A-4B and/or any of the transducer array positioning devices described herein), a histotripsy device 620 (e.g., structurally and/or functionally similar to the histotripsy device 120 of FIG. 1 and/or any of the histotripsy devices described herein) includes a transducer array 626 (e.g., functionally and/or structurally similar to the treatment transducer array 226 of FIG. 2B and/or any of the treatment transducer arrays described herein), a reservoir 628 (e.g., functionally and/or structurally similar to the interface 228 and/or any of the interfaces described herein), and a housing 629.

[00102] As seen in FIG. 6A, the cart 605 is a cart (e.g., stand, supporting structure, etc.) configured to support at least a portion of the robotic system 610. In some embodiments, the cart can be repositioned (e.g., via casters, wheels, etc.) to a desired location. The cart, as seen in FIG. 6A includes a display (e.g., functionally and/or structurally similar to the input/output device 256 of FIG. 2A). The display can be used by a user to monitor and/or alter the functionality of the system 600. The cart 605 is coupled to a proximal end of the robotic system 610. The distal end of the robotic system 610 is operatively coupled to the histotripsy device 620 and is configured to position the histotripsy device 620 and an associated focal volume in three-dimensional space relative to the cart 605. [00103] The positioning arm 616 of the robotic system 610 is configured to be operated to position the histotripsy device 620 to engage the patient P, as seen in FIG. 6B. In some embodiments, the positioning arm 616 is configured to position the histotripsy device 620 with five DOFs (e.g., three prismatic and two rotatory, any combination of prismatic and rotary, etc.). The positioning arm 616 moves the histotripsy devices 620 to an area of the patient P that is adjacent to the treatment area. As further seen in FIG. 6B, the reservoir 628 (e.g., container, tank, bladder, etc.) is configured to be positioned against the patient P. The reservoir 628 is a container that is filled with an interfacing fluid that is configured to both cool the transducer array 226 and to allow for the pressure waves from the transducer array 226 to be delivered desirably to the focal volume. In some embodiments, the surface between the reservoir 628 and the patient P can be coated in a fluid, gel, etc., that further allows for pressure waves to travel to the focal volume.

[00104] As seen in FIGS. 6C-6D, which show the system 600 with the reservoir 628 removed, the transducer array positioning device 618 is coupled to a distal end of the positioning arm 616. The transducer array positioning device 618 is covered by a housing 629 to prevent the positioning device 618 from damage and/or contaminants. The transducer array positioning device 618 is configured to position the transducer array 626 in three-dimensional space within the reservoir 628 such that the focal volume is moved within the treatment region. The transducer array positioning device 618 is configured to move the focal volume along a treatment path so that the transducer array 626 can treat the treatment region using boiling histotripsy.

[00105] FIG. 7 depicts the system 600 treating a patient P. The reservoir 628 is shown as translucent to show the fluid F stored within. The transducer array 626 is disposed within the fluid F. The transducer array 626 is configured to be arranged as to induce boiling histotripsy at the focal volume V. The transducer array 626 is configured to be able to be moved by the transducer array positioning device 618 throughout the fluid F within reservoir 628 to move the focal volume V within the patient P and to deliver treatment across a three-dimensional treatment area.

[00106] Referring generally to FIGS. 8A-10C, various views and configurations of a portion of a robotic system (e.g., functionally and/or structurally similar to the robotic system 110 of FIG. 1 and/or any of the robotic systems described herein) of a HIFU system (e.g., functionally and/or structurally similar to the system 100 of FIG. 1 and/or any of the systems shown herein) are shown, according to embodiments. The robotic system includes a transducer array positioning device 818 (e.g., structurally and/or functionally similar to the micro positioning device 218 of FIG. 2C, the transducer array positioning device 418 of FIGS. 4A-4B, and the transducer array positioning device 618 of FIG. 6D). The transducer array positioning device 818 is coupled to a histotripsy device 820 (e.g., functionally and/or structurally similar to the histotripsy device 120 of FIG. 1 and/or any of the histotripsy devices described herein) including a transducer array 826 (e.g., structurally and/or functionally similar to the treatment transducer array 226 of FIG. 2B and/or any of the transducer arrays described herein) and an imaging transducer 824 (e.g., structurally and/or functionally similar to the imaging transducer 224 of FIG. 2B and/or any of the imaging transducers described herein). The transducer array positioning device 818 is configured to move and/or orient the transducer array 826 and/or the imaging transducer 824 in three-dimensional space to move the position of a focal volume V. The imaging transducer 824 is coupled to the transducer array positioning device 818 via an imaging array positioning device 819 (e.g., functionally and/or structurally similar to the imaging array positioning device 419 of FIG. 4A). As seen in FIGS. 9A-9B, the imaging transducer 824 is concentrically located to the transducer array 826. The transducer array 826 is configured to focus at and to provide treatment at a focal volume V.

[00107] The transducer array positioning device 818 includes multiple positioners for moving the histotripsy device in a three-dimensional space and/or for rotating portions of the histotripsy device. By moving the histotripsy device (or specifically, by moving the treatment transducers of the histotripsy device), the transducer array positioning device 818 can be configured to move a focal volume of the treatment across a three-dimensional area to treat a larger volume of target tissue. The transducer array positioning device 818 includes a first positioner 818a, a second positioner 818b, a third positioner 818c, and a rotational positioner 818d, arranged in series (e.g., collectively referred to as the “positioners”). As seen schematically in FIGS. 13A-13B, the first positioner 818a (e.g., first positioner 1318a) is configured to provide translational movement along an x-axis, the second positioner 818b (e.g., second positioner 1318b) is configured to provide translational movement along a y-axis, and the third positioner 818c (e.g., third positioner 1318c) is configured to provide translational movement along the z-axis. Each of the first positioner 818a, the second positioner 818b, and the third positioner 818c is a prismatic joint that includes a motor and a leadscrew that, when the motor is actuated, converts the rotational motion of the motor intro translational motion along the associated axis. In some embodiments, the prismatic joints can include other devices configured to translated along the axes.

[00108] As seen in FIGS. 8A-8D, the positioners can be actuated between a minimum position and a maximum position. The positioners can be actuated to any point between the minimum position and the maximum position in any combination as to position the histotripsy device 820 in three-dimensional space. As seen in FIG. 8A, each of the positioners is at a minimum position. In FIG. 8B, the first positioner 818a is at a maximum position while the second positioner 818b and the third positioner 818c are at the minimum positions. In FIG. 8C, the second positioner 818b is at a maximum position while the first positioner 818a and the third positioner 818c are at the minimum positions. In FIG. 8D, the third positioner 818c is at a maximum position while the second positioner 818b and the first positioner 818a are at the minimum positions. FIG. 8E depicts a back perspective view of the transducer array positioning device 818. As shown, the first positioner 818a and the second positioner 818b are located on the same plane, while the third positioner 818c is vertically offset from the plane. The positioners are disposed on a supporting structure that is configured to support the weight of the positioners as well as reducing vibrations and/or the like.

[00109] As seen in FIGS. 10A-10C, the imaging array positioning device 819 is configured to translate and/or rotate the imaging transducer 824 relate to the transducer array 826. In some embodiments, the imaging array positioning device 819 may be configured to translate the imaging transducer 824 parallel to the axis associated with the third positioner 818c and rotate along a plane parallel to the plane associated with the first positioner 818a and the second positioner 818b. Generally stated, the imaging array positioning device 819 can be configured to translate and/or rotate the imaging transducer 824 in a three-dimensional space such that the imaging transducer 824 can be configured to be inserted toward the patient and/or rotated relative to the patient. As seen between FIG. 10A and 1 OB, the imaging array positioning device 819 is configured to extend the imaging transducer 824 along the z axis while the position of the transducer array 826 does not change. Similarly, between FIG. 10A and FIG. 10C, the imaging array positioning device 819 can rotate the imaging transducer 824 relative to the transducer array 826. In some embodiments, the range of motion of the rotation is about 180 degrees. Allowing for the imaging transducer 824 to rotate independently of the transducer array 826 allows for the target region to be treated while the adjusting the imaging transducer 824 to achieve a desired view of the target region.

[00110] As seen in FIGS. 10D-10I, the transducer array 826 can also be rotated. The rotational positioner 818d is configured to rotate the orientation of the transducer array 826 relative to the imaging transducer 824 and/or the other portions of the transducer array positioning device 818. In some embodiments, actuation of the rotational positioner 818d also rotates the imaging transducer 824. FIG. 10D, FIG. 10F, and FIG. 10H depict perspective views of three different positions of the rotational positioner 818d while the first positioner 818a, the second positioner 818b, and the third positioner 818c positions are kept constant. FIG. 10E, FIG. 10G, and FIG. 101 depict bottom views of the positions shown in FIG. 10D, FIG. 10F, and FIG. 10H, respectively. FIGS. 10D-10E depict the rotational positioner 818d in a zero-position. FIGS. 1 OF- 10G depict the rotational positioner 818d rotated about 45 degrees in a first rotational direction. FIGS. 1 OH-101 depict the rotational positioner 818d rotated about 45 degrees in a second rotational direction opposite the first rotational direction. In some embodiments, the range of motion of the rotational positioner 818d can be about 180 degrees.

[00111] FIGS. 11A-11B depict various views of a reservoir 1128 (e.g., functionally and/or structurally similar to the interface 228 of FIG. 2B, the reservoir 628 of FIGS. 6A-6B and FIG. 7, and/or any of the interfaces described herein), according to embodiments. The reservoir is a container, tank, etc. defining an internal volume and configured to store a fluid for cooling a transducer array and for providing desired acoustic coupling between the transducer array and the patient. The reservoir 1128 includes a body bottom or bottom housing 1128a, a body top or top housing 1128b, a membrane 1128c, an interface ring 1128d, and a transmission window 1128e. In some embodiments, the reservoir 1128 may be disposable after usage. For example, a new reservoir 1128 may be used for each patient and/or procedure. In some embodiments, the reservoir 1128 can be sanitized and reused.

[00112] The body bottom 1128a and the body top 1128b define the internal volume and are configured to generally store the fluid. In some embodiments, the body bottom 1128a is formed of one or more material. In some embodiments, the body bottom 1128a includes at least a portion that is formed of a compliant (e.g., deformable, conformable, etc.) material that is configured to conform to the patient during use. In some embodiments, the body bottom 1128a includes a portion that is formed of plastic, polymer, silicone, rubber, or other suitable material. In some embodiments, the body bottom 1128a is formed of a rigid material (e.g., hard plastic, metal, etc.) In some embodiments, the body bottom 1128a is clear or translucent, e.g., to allow for the transducer array to be visible within the reservoir 1128. The shape and/or rigidity of the body bottom 1128a can be changed depending on the target anatomy so that the reservoir 1128 can engage the patient for effective treatment. For example, a larger body bottom 1128a can be used to target a larger region of patient anatomy. As another example, the body bottom 1128a can be designed to have a curvature that conforms to the general shape of patient anatomy depending on the area of treatment, e.g., breast, abdomen, chest, arm, leg, etc. The body bottom 1128a defines an aperture that is configured to receive the transmission window 1128e. As such, the body bottom 1128a can be configured to support the transmission window 1128e. The transmission window 1128e is formed of a material that allows for ultrasound pressure waves to be transmitted therethrough. For example, the transmission window 1128e can be formed of a thin layer (e.g., about 0.05mm) of clear plastic. In some embodiments, the transmission window 1128e is configured to deform to the patient. In some embodiments, the interface between the body bottom 1128a and the transmission window 1128e is formed of a rigid plastic ring. The interface can be configured to hold and/or support the window 1128e.

[00113] The body top 1128b extends away from the body bottom 1128a opposite the transmission window 1128e. The body top 1128b can be formed of a rigid material (e.g., plastic, metal, etc.), or a more rigid material than the body bottom 1128a. In some embodiments, the body top 1128b is clear or translucent. The body top 1128b defines a lip that is configured to be detachably coupled to a housing 1129 (e.g., functionally and/or structurally similar to the housing 629 of FIG. 6A-6C), as seen in FIG. 11C. In some embodiments, the reservoir 1128 can include a unique identifier that is recognized by a histotripsy device. For example, the unique identifier can include a QR code, an RFID, and/or the like. In embodiments, a processor (not depicted) that is onboard the histotripsy system can be configured to read the unique identifier and confirm that the correct container or reservoir (e.g., suitable for the patient treatment, or one that has been authorized for use) has been attached to the histotripsy system before allowing operation of the histotripsy device. In some embodiments, the unique identifier can be used to ensure that a reservoir 1128 is not reused by confirming a usage state prior to enabling operation of the histotripsy device.

[00114] Within a space defined by the body top is the membrane 1128c and the interface ring 1128d. The membrane 1128c is an elastic membrane that is bonded to the body top 1128b. The membrane 1128c allows for relative motion between the housing 1129 and the full range of motion of the histotripsy device to provide a water-tight seal. Specifically, the membrane 1128c is configured to allow for the histotripsy device to be positioned without kinematic constraint (e.g., enabling motion of the histotripsy device). For example, the forces, moments, etc. exerted on the histotripsy device by the membrane 1128c are below a threshold that would affect the motion of the histotripsy device.

[00115] The interface ring 1128d is configured to allow for the system to sense the positive engagement of the interface ring 1128d and the transducer array of the histotripsy device, thus indicating a water-tight seal. The water-tight seal allows the fluid to remain within the reservoir and to not damage components of the system that may be damaged by the fluid, e.g., portions of the robotic system that sit above the reservoir such as the transducer array positioning device and/or imaging array positioning device. The water-tight seal is configured to accommodate the movement between the reservoir 1128 and the histotripsy device. [00116] FIG. 12 depicts a fluid flow path of a HIFU system 1200 (e.g., functionally and/or structurally similar to the system 100 and/or any of the systems described herein, according to embodiments. The system 1200 includes a cart 1205 (e.g., structurally and/or functionally similar to the cart 605 of FIGS. 6A-6D) including a pump 1206, a fluid source 1207, and a temperature control 1208. The system 1200 includes a robotic system 1210 (e.g., functionally and/or structurally similar to the robotic system 110 of FIG. 1 and/or any of the robotic systems described herein) and a reservoir 1228 (e.g., functionally and/or structurally similar to the interface 228 of FIG. 2B and/or any of the interfaces and/or reservoirs described herein).

[00117] The fluid flow path is configured to flow between the cart 1205 and the reservoir 1228 via the robotic system 1210. In some embodiments, the fluid flow path can include one or more set of conduits for moving fluid from the cart 1205 to the reservoir 1228 and fluid from the reservoir 1228 to the cart 1205. The fluid source 1207 is configured to store at least a quantity of fluid that can fill the reservoir 1228 to a desired level (e.g., to cover the transducer array). In some embodiments, the fluid source 1207 can include and/or be coupled to a temperature control 1208 configured to regulate the temperature of the fluid to maintain the temperature of the fluid at a set temperature. Specifically, the temperature control 1208 is configured to cool fluid. In some embodiments, the temperature control 1208 can include an active cooling system (e.g., cooling unit, refrigeration system, etc.) and/or a passive cooling system (e.g., heat sink, etc.). The pump 1206 (e.g., peristaltic pump, etc.) is configured to pump fluid between the fluid source 1207 and the reservoir 1228.

[00118] During operation, the system 1200 may determine when the reservoir 1228 is coupled. In response to determining that the reservoir 1128 is coupled, the system 1200 may actuate a latch to secure the reservoir 1128 while fluid is disposed within. The system 1200 may include generating a display on a screen of the cart indicating that the reservoir 1128 is coupled and that the reservoir 1228 can be filled with fluid. After receiving an input from the user, the pump 1206 can be activated to fill the reservoir to a predetermined level. The level of fluid in the reservoir 1228 can be monitored during filling and/or during treatment. If the level of fluid is outside of a predetermined range, the pump 1206 can be activated to return the level of fluid to the predetermined range. Similarly, the temperature of the fluid in the reservoir 1228 can be monitored as to keep the temperature in a predetermined range. If the temperature is outside of the predetermined range, a combination of pump fluid out of the reservoir 1228 and pumping fluid into the reservoir 1228 can be used to return the fluid temperature back within the predetermined range. In some embodiments, fluid is pumped out of the reservoir 1228 after treatment has completed and/or after receiving an input from a user. After the fluid level is below a minimum threshold, the latch may disengage the reservoir 1228.

[00119] FIGS. 14A-14L depict various views and configurations of a portion an alternate robotic system of a HIFU system, according to embodiments. Specifically, an alternate embodiment of a transducer array positioning device 1418 is shown. The transducer array positioning device 1418 is functionally and/or structurally similar to any of the transducer array positioning devices described herein. The transducer array positioning device 1418 is a delta robot that includes three joints, and a rotational positioner configured to translate a histotripsy device 1420 (e.g., structurally and/or functionally similar to the histotripsy devices described herein).

[00120] As seen in FIG. 14A, the transducer array positioning device 1418 includes a first positioner 1418a, a second positioner 1418b, a third positioner 1418c (collectively referred to as the “delta positioners”), and a rotational positioner 1418d. The delta positioners are configured to move the histotripsy device 1420 through three-dimensional space (as seen in FIG. 14B) through an interface 1428 (e.g., functionally and/or structurally similar to any of the interfaces described herein), as seen in FIG. 14 A. In some embodiments, each of the delta positioners can be prismatic delta arms and/or revolute delta arms, and/or a combination thereof. Each of the delta positioners includes a motor and a leadscrew that is configured to linearly translate a proximal end of an associated arm that is coupled to the histotripsy device 1420 on the distal end. The combination of the delta positioners translating, as well as the rotation of the rotational positioner 1418d can position the histotripsy device in three-dimensional space with four DOFs. As seen in FIGS. 14C- 14D, the delta positioners are configured to position a focal volume V associated with a transducer array 1426 (e.g., functionally and/or structurally similar to the transducer arrays described herein) and/or the imaging transducer 1424 (e.g., functionally and/or structurally similar to the imaging transducers described herein).

[00121] FIGS. 14E depicts the delta positioners in a full retracted position (e.g., at a vertical maximum along a first axis) and FIG. 14F depicts the delta positioners in a fully extended position (e.g., at a vertical minimum along the first axis). The delta positioners can also allow for movement along a second and a third axis, as seen in FIGS. 14E-14F, which depict the delta positioners moving the histotripsy device to the outer bounds of the range of motion. FIGS. 14I-14L depict how the

[00122] FIGS. 15A-16F depict various configurations of robotic systems (e.g., structurally and/or functionally similar to the robotic systems described herein), according to embodiments. The various configurations include different kinematic chains for controlling the position of therapeutic transducers (e.g., functionally and/or structurally similar to the transducer arrays described herein) and/or ultrasound imagers (e.g., functionally and/or structurally similar to the imaging transducers described herein). The configurations can include positioners (e.g., functionally and/or structurally similar to the positioners described herein) for controlling motion along an x-axis, a y-axis, a z-axis, a roll axis, and/or the like.

[00123] FIG. 15A depicts a robotic system with an x-axis positioner, a y-axis positioner, and a z axis positioner in series that are configured to position both the therapeutic transducer and the ultrasound imager. FIG. 15B is similar to the robotic system of FIG. 15 A, but a delta robot is used instead of the x-axis positioner, the y-axis positioner, and the z-axis positioner.

[00124] FIG. 15C depicts a robotic system with an x-axis positioner, a y-axis positioner, and a z axis positioner in series that are configured to position the therapeutic transducer and the ultrasound imager, with the ultrasound imager additionally moved by an imager insertion positioner in series with the z-axis positioner. FIG. 15D is similar to the robotic system of FIG. 15C, but a delta robot is used instead of the x-axis positioner, the y-axis positioner, and the z-axis positioner.

[00125] FIG. 15E depicts a robotic system with an x-axis positioner, a y-axis positioner, and a z axis positioner in series that are configured to position the therapeutic transducer and the ultrasound imager, with the ultrasound imager additionally moved by an imager roll positioner in series with the z-axis positioner. FIG. 15F is similar to the robotic system of FIG. 15E, but a delta robot is used instead of the x-axis positioner, the y-axis positioner, and the z-axis positioner.

[00126] FIG. 15G depicts a robotic system with an x-axis positioner, a y-axis positioner, and a z axis positioner in series that are configured to position the therapeutic transducer and the ultrasound imager, with the ultrasound imager additionally moved by an imager insertion positioner and an imager roll positioner in series with the z-axis positioner. FIG. 15G is similar to the robotic system of FIG. 15H, but a delta robot is used instead of the x-axis positioner, the y- axis positioner, and the z-axis positioner.

[00127] FIG. 16A depicts a robotic system with an x-axis positioner, a y-axis positioner, a z axis positioner, and a transducer roll positioner in series that are configured to position the therapeutic transducer and the ultrasound imager. FIG. 16B is similar to the robotic system of FIG. 16A, but a delta robot is used instead of the x-axis positioner, the y-axis positioner, and the z-axis positioner. [00128] FIG. 16C depicts a robotic system with an x-axis positioner, a y-axis positioner, a z axis positioner, and a transducer roll positioner in series that are configured to position the therapeutic transducer and the ultrasound imager, with the ultrasound imager additionally moved by an imager insertion positioner in series with the z-axis positioner. FIG. 16D is similar to the robotic system of FIG. 16C, but a delta robot is used instead of the x-axis positioner, the y-axis positioner, and the z-axis positioner.

[00129] FIG. 16E depicts a robotic system with an x-axis positioner, a y-axis positioner, a z axis positioner, and a transducer roll positioner in series that are configured to position the therapeutic transducer and the ultrasound imager, with the ultrasound imager additionally moved by an imager insertion positioner and an imager roll positioner in series with the z-axis positioner. FIG. 16F is similar to the robotic system of FIG. 16E, but a delta robot is used instead of the x- axis positioner, the y-axis positioner, and the z-axis positioner.

Examples

Transducers

[0001] FIG. 17 depicts fluid channels of a transducer device. In some embodiments, the transducers described herein can be used for boiling histotripsy. The fluid channels can be used for delivering fluid (e.g., degassed water, etc.) to a transducer for cooling. In some embodiments, the fluid channels are shown integrated into a detachable ultrasonic (US) imaging probe that mounts to the internal of the transducer, sealing off on the transducer with an O-ring and allowing fluid flow into and out of the highlighted fluid flow paths. This fluid is utilized to transfer acoustic energy from the transducer to the target and having active fluid flow that is laminar (vs turbulent) helps regulate the water temperature providing a heat sink to the transducer (in addition to coupling), and ensuring bubbles are not created by introducing (turbulent flow).

[0002] FIG. 18-19 depict various views of a transducer focusing element and components of the transducer device. In some embodiments, the transducer device has a focus (e.g., f number) less than 1 to concentrate the energy outputted by the transducer device and allows for shallower energy delivery. In this transducer configuration the PZT sectors are uniform and symmetric around a circular hole for a round imager. All the PZT elements are the same. FIGS. 20-22 depict various views of a transducer coupled to a transducer focusing element. In some embodiments, the transducer is an LI 5 probe. In this configuration a ‘rectangular’ cut out has been placed in the lens to allow for a linear off the shelf (OTS) probe to fit. Between the LI 5 probe and the surface of the lens a flexible membrane material, or gasket material can be placed to accommodate a variety of shapes or other off the shelf probes that fit into the cavity of the lens. When placing the rectangular cut out in the lens the PZT elements become non-symmetric, and the leads are then attached radially outward (away from center), or where the distance between the flat bottom of the PZT and the concavity of the lens ellipse is the greatest.

[0003] FIG. 66 depicts a histotripsy device, according to an embodiment. The histotripsy device, if configured with an 85 focus depth, a single f number of 1, and can operate at a frequency of 1 MHz. This design could be modified to have an F# of .75 to F# 1.35 achieving different depths but would fit in the same housing and work with the same center US probe. This could lead to a variety of different transducers tuned for specific depths that all have the same attachment methods etc. In some embodiments, the histotripsy device includes a coaxial image (e.g., P5-1L15-A6- Cardiac Imager) and a nav imager (e.g., CR-2R60S-3). In some embodiments, the histotripsy device includes a lens with two f numbers, an f number relative to the major axis that is greater than 1 and an f number relative to the minor ellipse axis that is one.

[0004] While fiducial trackers such as the one depicted in FIG. 66 are used in medical devices, they can be challenging to implement in real operating rooms. They can be obstructed, bumping them can impact their precise calibration, and their fundamental precision is often ~.5mm or worse (depending on the exact system). FIG. 94 depicts a histotripsy device without a fiducial tracker and generally improves the accuracy, removing the possibility of obstruction, and the need to run hand-eye calibration to register frames of reference, this is done by using another known reference frame. In one embodiment, a robot, which is already designed for precision and rigidity, and is already rigidly mounted to the relevant sensors and end-effectors.

[0005] This can be done with any sensor that is capable of locating itself in 3D space. In the case of the robot, the encoders can enable this. The same effect could be achieved more cheaply with similar encoder tracked joints under manual drive control. This has the advantage of being easier to manipulate manually and being much lower cost.

[0006] By doing this the problem from tracking absolute positions through a complex chain of transforms between reference frames into a much simpler problem of relative motion, using known joint geometry (often even fixed geometry).

[0007] FIG. 67 depicts a transducer lens, according to an embodiment. The lens includes a 110mm focus depth, an F number of about 1 , an output frequency of 1 MHz, and 18 element channels. In some embodiments, the histotripsy device includes a lens with two f numbers, an f number relative to the major axis that is greater than 1 and an f number relative to the minor ellipse axis that is one. The lens includes a coaxial imager (e.g., CR-2R60S-3 (Nav current imager)) with z-axis translation. The lens is sealed via gaskets and/or O-rings. A gasket was placed in the groove in lieu of epoxy enabling the device to be disassembled / serviced and ultimately replace the lens if necessary, thus allowing for rework/maintenance. The lens does not need, but can be used with, a Y adapter or a cardiac imager (e.g., P5-1L15-A6-).

[0008] FIG. 78 depicts a transducer device sleeve/housing, according to an embodiment. The housing enables the lens to be mounted with screws that are radially external to the gasket/O-ring, enabling the lens to be removed from the housing while being watertight. Additionally utilizing the built in dove tail slide and off the shelf transducer mounting block the off the shelf axial transducer can be adjusted to align the focus of the handheld US probe to the focus of the transducer. This can be done by loosening the dove tail attachment and using a hex key through the holes in the housing to loosen and adjust the assembly up and down. This could ultimately be done by a motorized stage and calibration setup vs the manual adjustments as depicted.

[0009] FIG. 69 depicts a sealing interface of a transducer device, according to an embodiment. A lens is sealed via two gaskets with bolts outside of the sealing surfaces. There are two sealing surfaces, one external and at the bottom of the lens and one internal at the top of the transducer housing. Both prevent fluid from entering the PZT area. FIG. 70 depicts a top view of the sealing interface. The top can be sealed by another piece for calibration. For example, a gasket and bolt circle/eclipse can be used with the same gasket. Wires or leads can come out of slots and be sealed as to not have to seal that portion and leave open. The slots are for the ground and power wires, they can be potted to create a waterproof seal or custom waterproof connectors could be installed in these areas to enable the lens to detach or attach via a connector instead of hard wired / soldered leads. In this specific design based on the depth of 110 mm the housing and the exit holes (exit ovals) were designed to be above the internal sealing interface so the wire house would not have to be sealed but could remain open and would be controlled to not submerge the transducer fully in water etc. preventing fluid flow into the PZT cavity area. Additionally this would allow us to utilize a thermal camera to look in at PZT temperature and or flow air down into the cavity to help keep the back side of the PZTs cool, too. FIG. 71 depicts a sealing interface with an imager (e.g., ultrasound, etc.). The sealing interface can include a double O-ring to form a seal.

[0010] FIG. 72 depicts views of fluid flow channels for delivering fluid to an imager, according to an embodiment. The fluid flow channels can include 2 fluid holes on the front and back for bubble removal and/or cooling. The holes are 2.5 mm to allow for a tube to be inserted. In some embodiments, the holes can allow for a twist or nozzle item to be coupled to or inserted. In some embodiments, the size of the hole is not important. There are just multiple and they are integrated into the housing of the off the shelf imager (since the imager doesn’t have them built in) to allow flow into the acoustic cavity and or more importantly to enable suction and flow to be altered or changed among the 4 holes to enable bubble removal when they accumulate when placing in a water bath or filling bladder up with water.

[0011] FIG. 73 depicts loading of piezoelectric transducers (PZT) during sealing. The bolt circles are outside of the sealing interface. Gaps are set to limit loading. Top screws, circled in red, go into inserts into the lens. FIG. 73 shows the intended contact plane for the lens to the housing to ensure the O-ring is uniformly compressed. The circled interface shows a screw pulling the other O-ring sealing interface into compression but utilizing a threaded insert vs trying to tap and thread the lens which is brittle when it comes to machining but great at transmitting the acoustic energy. Because the material is brittle, it is undesirable to thread directly into it. Instead the insert is there to enable the engagement of the upper O-ring without damaging the lens.

[0012] FIG. 74 depicts a transducer device lens, according to an embodiment. The lens has an elliptical shape and includes a plurality of elements. FIG. 75 depicts the focal length and axes of the lens of FIG. 74. FIG. 75 depicts the sizes of different lens elements of the lens of FIG. 74. The lens balances power from each piezoelectric component (e.g., PZT). The largest element has an area of 185.4 mm² and the smallest has an area of 169.1 mm² with a difference of 9.6%. Fig. 75 highlights that there was a surface area difference between the PZTs . Based on a configuration that runs 2 PZTs per driver board it is desirable to match the areas as close as possible since it was not possible to independently power the PZTs meaning that the PZT with more area needs more power leading to more power to be dumped into the smaller PZT leaving it at risk of higher experienced power dump potentially causing heat or faster failure. FIG. 77 depicts how the ellipse associated with the lens of FIG. 74 is split into approximately equal areas. FIG. 79 depicts the total area of the piezoelectric elements of the lens of FIG. 74. In some embodiments, the total piezoelectric area is 3157 mm². FIG. 79 depicts that this smaller area than that of FIG. 78 transducer can reduce the surface area when you lower the f number. FIG. 78 depicts a transducer device with a multi-element lens, according to an embodiment. In some embodiments, the lens has a total area of 5087 mm².

[0013] FIG. 80 further depicts the lens of FIG. 74 including the lens integrated into a transducer element. The lens has a double f-numbers and is divided into 18 sections. Each section is split in the middle via a plane, then an elliptical a-b dimensions is used to revolve (e.g., pattern revolve). The lens includes steps above and below which are blended with ribs above and below thus reducing the effective area. The ribs are blended together via sweeps to reduce the sharp edges resulting from the utilization of flat PZT segments, causing the top picture to have a stepped appearance. These stepped appearances would be not ideal for a rubbing a water containing membrane, skin, cleaning, and a stress concentrator for a lens vibrating at the high frequency. So to make the lens stable beyond just BH, the ribs were added. The elliptical shape has a specific focus, the f-number has a range, giving it properties between what the calculated f-number of the major or minor axis. The range of the f-number varies from the major and minor axis values but is between the two. FIGS. 81-82 depicts the lens of FIG. 74 with M3 holes for Ml .6 heat inserts. The importance of the attachment at the inner and outer seal interface is to allow compliance at the screw interface via the screw and insert vs directly transmitting the bolt load into the lens potentially causing it to bend, creating a compressive bending movement between the two sealing screws, causing a subsequent compressive force on the epoxy embedded PZT changing the impedance of the PZT or limiting its ability to vibrate causing damage from excessive heat generation and/or cracking the ceramic PZT from the load needed to generate a good seal. The insert will come loose before it damages the lens/PZT interfaces.

[0014] FIG. 83 depicts piezoelectric consumption, according to an embodiment. In some embodiments, 6-8 raw stock PZTs are used per transducer. In some embodiments, the area of the PZT is 3157 mm² and the area of the disk is 1963.49541 mm². 1.6 Disks = 2 Disks assuming imperfect usage of PZT.

[0015] FIG. 84 depicts a bladder attachment to the transducer device, according to an embodiment. The bladder attachment includes a sealing flange on housing. The sealing flange is external to have a feature for bladder attachment. In some embodiments, the sealing flange can include bolt holes to improve loading.

[0016] FIG. 85 depicts a transducer device sleeve with access ports for inserting tools. Similar to FIGS. 68, 70, 72, and 86, FIG. 85 shows how a user could insert a tool to adjust the dove tail groove alignment of the imager and the transducer with a readily available hand tool. Could be utilized for calibration and or maintenance.

[0017] FIG. 86 depicts views of a transducer device with an elliptical lens, according to embodiments. Additionally shown is a series of 8 clamps that go around the elliptical housing perimeter that hooks onto an elliptical clamp ring. Between the ring and the sealing surface on the transducer, membrane material can be compressed via the clamps and the metal surface creating a seal allowing the bladder to be filled via the holes in the imager. The clamps are individually mounted on dovetail groove interfaces on the transducer housing so the compression of the clamp interface/latches could be dialed in to create a fluid seal but not over burden the user from excessive force. As seen in FIG. 88, the lens has a rectangular opening, 110 mm focus depth, a double f- number (e.g., 1.0 in the y axis, and 0.815 in the x axis), a 1MHz output frequency, 18 element channels, and a coaxial imager (e.g., CR-2R60S-3 (Nav current imager)). The lens can be sealed via gaskets and/or O-rings and includes epoxy channels as backup channels. As seen in FIG. 89, the lens has a piezoelectric (e.g., PZT) area of 9288 mm².

[0018] FIG. 88 depicts views of a transducer device with an elliptical lens, according to embodiments. FIG. 87 shows alternative view of transducer with bladder clamp rings and details dimensions of the lens design. It also show individual water seal for wire assemblies integrated into the housing to allow more housing material to be removed and the individual channel leads to not need to be potted by an additional step (the nuts are tightened down and creates a seal around the OD of the wire jacket (this is an OTS part), but doing this also enables the housing material removal as stated previously to be on the same plane as the other exists/sealing interfaces vs other embodiments where the power line exit from the housing was placed higher to prevent fluid flow. This embodiment enables individual channels to be serviced or fixed without having to undo everything

Robotic Movement

[0019] Ablating tissue at a pulse repetition frequency (PRF) of 1 Hz - 3 Hz is slow, delivering only 1 energy pulse per second. Each treated spot is affected by the acoustic energy for a fraction of the second and needs to rest for the remaining portion of the second to remain within the range of boiling histotripsy (BH). While a BH transducer is capable of treating tissue at a higher PRF, the tissue must rest. By moving the BH transducer during treatment, we can achieve an experienced effective PRF of <1 Hz, thereby giving the tissue plenty of time to rest. The majority of the existing methods focus on ablating in a rectangular grid. Currently, there are no methods to ablate a circular sheet/volume of tissue. However, BH transducers described herein can be moved in concentric circles during treatment at strategic speeds and spacings to optimize treatment times. For example, this may be why the robot is moved; energy is applied during .01 to 0.03 seconds, rest .99 to .97 second and move the robot during that time. When the robot is returned to the starting position that spot will experience the required energy delivery to maintain and create BH lesions. So from the spot of treatment it gets 1 Hz of treatment but the transducer fires faster as it moves to several spots.

[0020] For larger volumes, it is advantageous to be able to alter the pulse rate of the transducer. While ablating in concentric circles (as seen in FIGS. 23-25), the number of lesions increases as the radius increases. A path for creating lesions can be developed for circles and concentric circles using the following equations. Ablating the circumference of a circle of average radius R with spot size diameter d, minimum wall thickness tmin, maximum pulse repetition frequency f, and N shots per location is depicted in FIG. 23. The following equation can be used to determine the number of lesions per circle n: [0021] Number of lesions per circle n: n = I ⁼

[0022] To optimize lesion packing, a minimum thickness t_min of 0.4 - 0.7 times the lesion diameter is desirable, e.g., based on a minimum thickness of 0.5d when lesions are optimally packed.

[0023] For a singular circular lesion, the transducer can be moved continuously in the circle of radius R with constant velocity v. For smaller circles where n < f, the PRF can be adjusted to match the number of shots. An equation for velocity is: v = 2nR X 1 Hz (requires N revolutions).

[0024] For large circles, the velocity changes as a function of the number of lesions created.

[0025] Several methods for selecting a velocity value for larger circles can be used (e.g., Eq. 1 and Eq. 2 below).

[0026] Eq. 1 : Requires N revolutions: v =

2nR f

[0027] Eq. 2: Requires up to (n-l)N revolutions: v = — — p

[0028] Eq 1. is predictable, however lesions are overlapping.

[0029] Eq. 2 includes term p, which can be a small integer coprime with n. With Eq. 2, it can be more difficult to calculate number of revolutions. Eq. 2 can be effective at placing lesions strategically with ample spacing (there are a number of exceptions, so this is most useful for when n is odd or not divisible by 3).

[0030] A complete volume of lesions can be created by stacking the concentric rings of lesions as seen in FIG. 24. For a lesion volume of maximum radius Rmax, the following radii may be used.

[0036] FIG. 25 depicts a sample array of lesions with R_max = 5mm, d = 1mm, t = 0.6mm. At a PRF of 6 Hz, and 10 shots per lesion, as an example, the method described herein is configured to ablate a 1 cm diameter circular sheet/volume in approximately 4 minutes.

Spot Size Characterization

[0037] In embodiments, a method can be used to deliver BH to optically clear gel to visualize the resulting damage in high definition and accurately measure a single BH lesion using a camera setup. The ability to create, visualize, and measure individual lesions can enable accurate evaluation of the output of a BH system, characterize treatment effects in response to a variety of factors, adjust a BH system output to create desired treatment effects, and plan larger treatment volumes. Test setup elements can include a camera with bellows and zoom lens, a moveable camera stage, a strong LED light with moveable light stage, an optically clear PA gel, a linear tank stage with control app, an app GUI to control treatment, an automated lesion measurement tool, a gel holding fixture, a tank, rubber mats, a magnetic gauge needle holder, and/or the like.

[0038] In use, the transducer is positioned over an optically clear block of PA gel in a tank of degassed deionized (DI) water, e.g., using an application interface and ultrasonic (US) feedback. A camera is positioned in front of the gel block and focused on the treatment area. A strong LED light source is positioned with the camera and the treatment focus to backlight the lesion that forms from the treatment. The aforementioned setup can be seen in FIGS. 26-27. BH is applied through the transducer into the gel block using a variety of treatment parameters. The lesion is actively monitored during formation using the camera as seen in FIG. 28.

[0039] After formation, the transducer is removed from the tank and a gauge needle that aligns with the center of the transducer is magnetically attached, as seen in FIG. 29. The tank is moved using the linear tank stage and the gauge needle is lowered into the tank using the robot so that the lesion and gauge needle are visible in the same frame on the camera, as depicted in FIG. 30. An image of the lesion with the gauge needle is captured using the camera. The image is then postprocessed using a processor implementing an automated lesion measurement tool which allows the user to put the image in grayscale and click to measure various lesion parameters (e.g., lengths and widths). An example of the post-processing is shown in FIG. 31. Lesion measurement data is collated and analyzed statistically. An example of the output is shown in FIG. 32 and depicts lesion measurement from spot size characterization.

Automated Lesion Measurement

[0040] Processing images of lesions is time consuming and tedious using ImageJ and other image measuring techniques. Tank setups can be highly inaccurate, prone to human error, and time consuming to setup and keep track of.

[0041] In embodiments, a method, generally shown in FIGS. 33-37, can include using a processor implementing a software tool to process images of lesions, automatically scaling the images and measuring lesions. A tank setup can be used to move the tank and gel block accurately and precisely. A system can be used for treatment and image processing automatically, e.g., with the click of a button or some other user input.

[0042] A software tool can be configured to process images of lesions, e.g., automatically scaling the images and measuring lesions. An automated lesion image capture system can include a tank fixturing setup to move a tank and gel block (fixed in the tank) to target, treat, and image lesions repeatedly, and a processor implementing software that can be used to control the robot, transducer, ultrasound probe, tank fixture and camera to automatically place lesions, move the tank, image lesions, and process lesion images.

[0043] FIG. 33 depicts a scaling process. Images of each lesion is set to a predetermined image scale, or includes a gauge needle to calculate the image scale (e.g., in mm/pixel). The software tool uses computer vision to find the bounding rectangle of the gauge needle. The width of the bounding rectangle and gauge needle diameter can be used to calculate pixel scale. For example, Pixel Scale [mm/pixel] = Needle Diameter [mm] / Pixel Width [pixel],

[0044] FIG. 34 depicts a measurement process. Lesion sizes can be measured by: 1) determining the overall boundary (red) and core boundary (yellow) of the lesion; 2) measuring the dimensions of the lesion in pixels (e.g., core width (blue) and core length (green)); and 3) converting pixels dimensions to lesion dimensions. Lesion measurement can be automated using computer vision, to speed up data collection process. Using an input lesion image and pixel scale, the software tool can output the length, width and core length/width of the lesion. For example, Lesion Dimension [mm] = Pixel Scale [mm/pixel] * Pixel Dimension [pixel]. FIG. 35 depicts the operation of the software tool including data fields, selection fields, and the like for processing images of lesions. [0045] FIG. 36 depicts multiple views of a tank fixture setup. The tank fixture moves the tank and its contents perpendicular to the camera (e.g., in 1 -axis movement) to enable treatment and imaging at different points in a gel block, without moving the treatment setup (e.g., robot + transducer) or the imaging setup (e.g., camera + light).

[0046] FIG. 37 depicts an example automated image capture system. The system is configured to, in addition to automating image processing, measure lesions, e.g., in real-time, immediately after they are formed. The image capture system includes a host compute device coupled (e.g., via ethernet, USB, or another wired or wireless communication channel) to a robot arm or linear actuator, a transducer, tank fixture (e.g., linear stage), and a camera. The transducer engages a gel block fixed using a block fixture in a water tank, which is coupled to the tank fixture configured to move the tank and gel block along 1 axis to target, treat, and image different parts of the gel block. The robotic arm or linear actuator is configured to list and lower the transducer. The transducer remains stationary during treatment. A LED light can be used to light the water tank. The camera is fixed in position and inline with the LED light to image lesions created by the transducer. The host compute device controls the camera, the transducer, ultrasound probe of the transducer, robot arm, and the linear stage. The host compute device can also process images captured in real time by the camera. The host compute device may be used to automatically place lesions, move the tank, image lesions, and process lesion images.

Needle Cannula Guide [0047] When doing the US sweeps of the anatomy (e.g., spine, breast, etc.), it is useful to have the ability to insert a needle to a location that has been determined to be of interest with the US and/or combination of US/MRI/CT scan. Because it is not always necessary to utilize needle insertion, it can be desirable to have it as an add-on or attachment to the robot, e.g., via an accessory. Such can maximize the robotic movement space while still enabling accurate needle guide placement that is positioned and angled by the robot (or, in other words, positioned relative to the robot). This allows for direct insertion to be completed by the surgeon or other medical practitioner.

[0048] FIG. 38 depicts various views of a needle guide sleeve, according to embodiments. The sleeve has fixed and/or adjustable needle angle insertion cannulas. The fit can be adjusted by tightening a semi moveable portion of the guide to squeeze down on the needle, allowing for insertion while helping limit wiggle or slop between the needle and hole.

Ultrasound Mount Setup

[0049] FIGS. 39-40 depict various exploded views of a mount for an ultrasound device, according to embodiments. FIGS. 39-40 depict all the components that go into the configuration and how they are assembled. Notably, the needle guide sleeve has symmetric wings that are in-line with the plane of the US probe enabling the needle to be tracked as soon as it comes in view of the US probe. The nest has two parts that enable the OTS (off the shelf) US probe to be locked into position relative to the robot with the mounts. The nest then has a registration lip that stops the movement of the needs sleeve so it can be put on the assembly after a sweep of the US probe on the patient as the winged needle areas increase the width of the assembly limiting the tilt capabilities of the robot. The lip and three prongs (teal arrow on needle sleeve) with corresponding notches on the nest housings drive alignment of the removable needle sleeve guide.

Spine Model

[0050] FIGS. 41-47 generally depict forming an anatomical model of a spine (e.g., gel spine phantom). In embodiments, the gel spine phantom is a low-cost model that can demonstrate and test both needle targeting and BH. The gel spine phantom can have multiple features or characteristics. For example, it can be MRI compatible, ultrasound compatible, lumbar spine embedded, include fiducial markers placed in clinically realistic locations, optionally includes a minimum of three fiducial markers, an ability to see BH induced damage, an ability to insert a tracked needle to the fiducial target, and visually transparent gel, to see embedded spine, etc.

[0051] The gel spine phantom is formed of and/or by a spine model, nylon threaded rod, nylon washers, male luer cap (e.g., Merit Medical component PN 101041006 OR 101031003), female luer lock (e.g., Merit Medical component PN 100916001 OR 102202001), plastic epoxy, bandsaw, drill and drill bits, ballistics gel, baking pan, oven, M4 steel threaded rods, and a holding fixture. [0052] In embodiments, forming the gel spine phantom includes the following steps:

1) Fully disassembling the spine model and removing the metal threaded rod, while keeping note of order and orientation of vertebral segments;

2) Reassembling with nylon threaded rod, leaving off the superior vertebral body (LI);

2a) using nylon washers and nuts and no metal;

2b) using no metal in the model;

2c) tightening down washers to avoid excessive flexion between vertebrae segments;

3) Fit checking with baking pan and remove the inferior end of sacrum with bandsaw to fit;

4) Assembling minimum 4 fiducials by attaching male luer caps to female luer locks and tightening (e.g., by hand);

5) Attaching the fiducials to the spine with epoxy, using a sufficient quantity of adhesive to avoid detachment during gel cooling, e.g., placing at least 3 fiducials, with a minimum of 2, on patient right side;

5a) Fiducial markers should be oriented such that the angle of the marker points towards Kambin’s triangle, with the colored cap facing outwards;

5b) It can be useful to place the non-colored tapered end into the divot (marked with green C in FIG. 41) between the superior articular process and the transverse process;

6) Drilling and tapping M4 holes into anterior side of spine, at MIN 2 vertebrae levels. Drill offset from center to avoid hitting threaded rod;

7) Counterboring the top of the threads to allow space for putty as seen in FIG. 42;

8) Threading on nylon rods;

9) Attaching spine with threaded rods onto holding fixture. Measuring the height of fiducial markers. Markers are desirably a maximum of 55mm from bottom of pan to reach with needle during targeting demo;

10) Filling the counterbore with putty, making sure to create a strong bond between plastic and metal rod, as seen in FIG. 43;

11) Assembling the spine into the suspension frame. Use a separate but identical pan to set height and position of the spine relative to the pan;

12) Turning on the oven to a set temperature, e.g., 290 degrees F for Humimic #1 or 309 degrees F for 10% Ballistic gel;

13) Spraying pan with mold release;

14) Melting gel in the pan by cutting up gel into pieces and putting it in the pan. For example, approximately 51b lOoz of Humimic #1, approximately 51b lOoz of 10% Ballistic, and/or the like. In some embodiments, the oven does not need to fully reach the set temperature. 15) Waiting approximately 3-4 hours so that the gel melts. Checking periodically;

16) Checking consistency is fully molten to the bottom of the pan with a silicone spatula;

17) Slowly placing spine and holding fixture onto pan, and moving to correct position. An ideal position can include an off-center position, with more space between the side of the pan and the side of the span with more fiducial markers;

18) Carefully placing pan in preheated oven;

19) Leaving the oven on for a set time period (e.g., 30 minutes);

20) After the set time period (e.g., 30 minutes), turning off the heat and cracking oven door, or otherwise creating conditions that allow for gradual cooling of the gel.

21) Maintaining for minimum 12 hours, to allow gel to cool slowly;

22) Taking the gel mold out and letting cool to room temperature for additional 2 hours;

23) To remove the gel from the pan:

23a) using a knife to gently release top edge of the gel from the pan.

23b) Pushing small rulers or other thin rigid items down the side of the pan to release the contact as seen in FIG. 44.

23c) Adding soapy water into the gaps created.

23d) Optionally using an ultrasound bath help release the gel from the pan.

23 e) Continuing releasing the edges and sides.

23f) Trying to get as much soapy water down the walls of the pan.

23g) Turning upside down and optionally shaking vigorously to get the gel to slide out of the pan;

24) Once released and dried, using a heat gun to melt the surface of the gel to make the gel phantom optically clear. As seen in FIG. 45, the phantom second from the left is one that has not been heat gun cleared yet;

25) If desired, inserting medical fiducials as seen in FIG. 46.

[0053] FIG. 47 depicts views of a custom designed and built spine model. To form the spine model, cooling the mold under vacuum pressure removes gas from the gel, which is good for visual clarity but prevents BH bubbles from appearing in the model. If the model is to be used to show BH, it cannot be formed under pressure. As such, leaving the model in the oven with the heat turned off and letting it cool naturally over time allows BH damage to show up more clearly in the gel. In some cases, this can be show up clearer in the Ballistics gel than Humimic gel.

Point Cloud Representation Interface

[0054] FIGS. 48-56 and FIGS. 90-96 depict images of an application interface used to operate and/or supervise a BH system during operation. FIG. 48 depicts an application interface including an ultrasound live view, ultrasound configuration options, waypoint configuration and control options, run and save controls, and robot controls. FIGS. 49-50 depict an application interface including robot control options and navigation options with a guidance overlaid on live ultrasound imaging, ultrasound configuration options, treatment settings and firing controls, and transducer calibration and configuration. FIG. 51 depicts an application interface including point and click selection on the ultrasound image, feature toggle options, a visualization of cone of acoustic treatment, a visualization of target anatomy, a list of target trajectories, a visualization of ultrasound plane and targeting trajectory, and access window controls that are disabled in the embodiment of FIG. 51. FIG. 52 depicts an application interface including live ultrasound view and configuration, feature toggle options, visualization of cone of acoustic treatment, a treatment pattern and settings and firing progress, a visualization of treatment pattern, and a visualization of target anatomy.

[0055] FIG. 53 depicts an application interface including live ultrasound view and configuration, feature toggles, visualization of an end-effector, treatment pattern and settings, firing progress, a visualization of treatment pattern, and a visualization of target anatomy. FIGS. 54-56 include file loading including ultrasound and preoperative images (e.g., MRI, CT, etc.), adjustments of voxel density for projection and reconstruction, toggles for various visualization features (e.g., point clouds, axes, meshes, etc.), image segmentation visualization (e.g., the red circle around the anatomy is identified as bone), and converted registration of pre-operative and intra-operative models. In FIG. 54, the models are converted to meshes. In FIG. 55, the models are converted to surfaces. In FIG. 56, the models are represented by point clouds.

[0056] Target selection, such as in FIG. 51, is used to select one or more points from a series of ultrasound images, allowing selection of any target seen in a sweep through a 3D volume. Treatment patterns and settings allow for the configuration of various targeting patterns, including cylindrical and cuboid. For each shape, the size and spacing of the treatment can be set. Additionally, the pulse sequence can be configured by adjusting PPP (Pulse Per Point), PRF (Pulse Repetition Frequency), Voltage, Current, Carrier Frequency, and Cycles per pulse. Visualization of treatment patterns shows the volume being treated, as well as each individual pulse lesion location. Individual lesion locations are represented by green ellipsoids in FIG. 90.

[0057] The cone of acoustic treatment represents the path through which the treatment energy will travel. The visualization of the end-effector shows an animation that previews the expected robot motion. The user can then press and hold a button to move the robot, during which time the visualized end-effector will match the real-time motion of the actual end-effector. There are several checkboxes and buttons towards the top of the screen that control the visibility of certain objects in the 3D scene. “Display skin” toggles visibility of the skin layer. This layer can be generated from segmentation masks that are created during the scanning procedure. If a surface segmentation is not available, a rough cylindrical approximation can be created instead.

[0058] “Display Axes” toggles the visibility of XYZ coordinate axes that represent the origin of the 3D scene. “Display Treatment End Effector”, “Display Treatment Cone”, and “Display Treatment Lens” all toggle visibility of different parts of the end effector. The last two are self- explanatory. The first one basically refers to all of the end effector except the cone and lens. “Display Transducer Blockage” toggles the visualization shown in FIG. 91. “Display Imaging Plane” toggles the visibility of the red plane in the 3D scene. The red plane illustrates the pose of the US slice with respect to the anatomy.

[0059] ‘ ‘Activate Clipping Plane” is a feature that is an extension of the imaging plane. This button toggles visibility of the appropriate US slice being overlaid on the US imaging plane. It also transforms the anatomy on one side of the plane to be semi-transparent while the other side remains opaque as seen in FIG. 92. “Flip Direction” simply toggles which side of the anatomy is semitransparent or opaque. It is only relevant when the clipping plane is activated. “See Through Anatomy” checkbox toggles the ability to see into an anatomical volume. When this checkbox is on, a small area of the anatomy where the user is hovering his/her mouse over becomes completely transparent, allowing the user to look at and interact with objects that may not initially have been visible. “Assess 3D Reconstruction” button allows the user to qualitatively compare the reconstructed anatomy with the segmented parts in the acquired US images as seen in FIG. 93. The yellow outline represents the contour of the reconstructed mass that would be visible in that specific US slice. The blue outline is a visualization of the segmentation result for that specific US slice. The more overlap between the two outlines, the better.

[0060] As seen in FIGS. 53, 54, and 55, voxel density determines how many points will be sampled in order to reconstruct the surfaces. Image segmentation shows the detected surfaces of the spine used to reconstruct the surfaces. Manual registration refinement tools are used to rotate and translate the resulting models relative to each other, in the event that the automated registration has any apparent error. The toggles enable and disable visualization of the meshes, points, and a set of axes to show frame of reference.

[0061] In some embodiments, a line of sight approximation tool can be used for assessing obstructions for targeting treatment volumes. This tool creates a line of site projection, showing the area on the skin where a transducer could be placed to have clear access to a selected treatment volume based on obstructions, focal depth, and angle with respect to the skin. Brighter colored areas on skin indicate access to greater fraction of treatment volume. Ripples in right image are segmentation artifact and do not convey any additional meaning. The treatment volume is small as seen in FIG. 96, but it can be seen as a yellow cube, just above the hip. Based on calculated access window areas, this tool can be used to quickly adjust various parameters, showing a projection to inform lens size and shape based on various target anatomy, as seen in FIG. 95. The square black plane represents the transducer face. White-colored areas indicate clear access. Gray box around white area indicates approximately simulated transducer shape. In this image, the transducer dimensions are 183mm x 142 mm.

[0062] An existing transducer design can also be evaluated as in FIG. 91. That portions of the transducer lens colored as red show the portion of the transducer that is obstructed by materials that will prevent acoustic transmission, such as bone and gas.

Geometric Simulation of Acoustic Access

[0063] FIG. 57 depicts an image from simulation showing an access window to help with aberration estimations. The image includes gas segmentation in blue, spine segmentation in bone color, and an acoustic beam path in red. The image additionally includes user adjustment options for transducer orientation, focal length, and diameters (or distances in a rectangular transducer). FIG. 58 depicts a representation of normalized pressure over a cross-section of tissue. The tissue is based on a real CT scan. The representation is formed using a combination of parameters that can be mapped directly from scan data, and segmentations which have properties that can be mapped from estimates typical to specific tissue types.

[0064] Starting with a CT scan, the sound speed and material density with a mapping from Hounsfield units can be estimated. Segmentation can then be performed, into all relevant tissues (e.g., bone, fat, gas, skin) and typical absorption factors for these tissues can be looked up. The 3D model (FIG. 57) shows line of site access window. The 2D simulation (FIG. 58) then runs a simulation to generate an estimated map of peak pressure.

[0065] The resulting peak pressure map is used to understand how well transducer energy will be focused during realistic clinical applications, suggesting the degree to which aberration correction will be required. This picture shows a significant amount of aberration, which both shifts the effective focus away from the intended target and spreads the energy out. In this example, this spread of energy strongly suggests that aberration correction is needed in order to successfully achieve BH. Similarly, the corrections can be back-calculated for this simulation, helping us to understand the timing offsets required for each element in order to correct the focus.

HIFU Beam Simulations

[0066] FIG. 59 depicts simulation results of peak positive pressure in the axial Z-r plane. P+ is the peak positive pressure. Z is the distance from the transducer, along the focal axis, r is the radial axis which is transverse to the focal axis. The simulation results can correspond to a BH, or other high-intensity focused ultrasound (HIFU), beam.

[0067] The simulation can include a nonlinear acoustic simulation tool that makes a number of simplifying assumptions to reduce this simulation to a problem that can be solve in minutes in order to estimate transducer design parameters, drastically speeding up development time for radially symmetric designs, or providing a starting point to start from when creating non- symmetrical designs.

Bayonet Bladder Attachment

[0068] FIGS. 60-65 generally depict various views of an example coupling mechanism between a transducer and a transducer interface (e.g., flexible membrane, bladder). The coupling mechanism (e.g., coupling system) can be a quick coupling mechanism that has been integrated into the transducer architecture to enable fast easy changing of the bladder. The system can include a retaining ring for the flexible membrane that can clip into place and/or be removed/replaced to replace the membrane material. The system can further include a bayonet attachment, a set of O- rings set on an attachment, a set of O-rings set on a transducer housing, and an outer ring that has one or more fluid flow channels, allowing fluid to flow into and/or be sealed under the transducer and/or in the membrane material.

As seen in FIG. 60, the coupling mechanism can be tapered for insertion ease and can include a tactical lock bump that corresponds to the flexible membrane being rotated into a locked position. As seen in FIG. 61, the coupling mechanism can include a snap feature that further couples the flexible membrane to the transducer. FIG. 61 further shows a fluid channel through which fluid can flow into an area below an internal O-ring to fill the flexible membrane. FIG. 62 depicts a transducer device including a silicon seal engaging and coupling to a flexible membrane via a coupling mechanism. FIG. 63 depicts an embodiment of a coupling mechanism that is integrated into a transducer device. FIG. 64 depicts a section view of a flexible membrane connecting via a bayonet connection. O-ring and glue locations are shown in FIG. 64. FIG. 65 further shows how the bayonet engages the membrane material to lock the flexible membrane to the transducer device.

[0069] In some embodiments, a gel puck can be attached to the transducer. Instead of a membrane, a preloaded gel pad is used to transmit acoustic energy. Inlets and outlets can still be used to allow for fluid to make sure there is a sufficient transmission layer between the gel and the lens surface.

[0070] In some embodiments, BH systems and devices described herein can include or be structurally and/or functionally similar to one or more elements from systems and devices described in International Patent Application No. PCT/US2022/081891, titled “SYSTEM AND METHOD FOR TISSUE INTERVENTION VIA IMAGE-GUIDED BOILING HISTOTRIPSY,” filed December 16, 2022, and U.S. Provisional Patent Application No. 63/627,762, titled “SYSTEMS, DEVICES, AND METHODS FOR NON-INVASIVE TREATMENT OF TISSUE USING BOILING HISTOTRIPSY,” filed January 31, 2024, the disclosure of each of which is incorporated herein by reference.

[0071] While various inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto; inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, and/or methods, if such features, systems, articles, materials, and/or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.

[0072] Also, various inventive concepts may be embodied as one or more methods, of which an example has been provided. The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.

[0073] As used herein, the terms “about” and/or “approximately” when used in conjunction with numerical values and/or ranges generally refer to those numerical values and/or ranges near to a recited numerical value and/or range. In some instances, the terms “about” and “approximately” may mean within ± 10% of the recited value. For example, in some instances, “about 100 [units]” may mean within ± 10% of 100 (e.g., from 90 to 110). The terms “about” and “approximately” may be used interchangeably.

[0074] Some embodiments described herein relate to a computer storage product with a non- transitory computer-readable medium (also may be referred to as a non-transitory processor- readable medium) having instructions or computer code thereon for performing various computer- implemented operations. The computer-readable medium (or processor-readable medium) is non- transitory in the sense that it does not include transitory propagating signals per se (e.g., a propagating electromagnetic wave carrying information on a transmission medium such as space or a cable). The media and computer code (also may be referred to as code or algorithm) may be those designed and constructed for the specific purpose or purposes. Examples of non-transitory computer-readable media include, but are not limited to, magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as Compact Disc/Digital Video Discs (CD/DVDs), Compact Disc-Read Only Memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier wave signal processing modules; and hardware devices that are specially configured to store and execute program code, such as Application-Specific Integrated Circuits (ASICs), Programmable Logic Devices (PLDs), Read- Only Memory (ROM) and Random-Access Memory (RAM) devices. Other embodiments described herein relate to a computer program product, which may include, for example, the instructions and/or computer code disclosed herein.

[0075] The systems, devices, and/or methods described herein may be performed by software (executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, a general-purpose processor (or microprocessor or microcontroller), a field programmable gate array (FPGA), and/or an application specific integrated circuit (ASIC). Software modules (executed on hardware) may be expressed in a variety of software languages (e.g., computer code), including C, C++, Java®, Ruby, Visual Basic®, and/or other object- oriented, procedural, or other programming language and development tools. Examples of computer code include, but are not limited to, micro-code or micro-instructions, machine instructions, such as produced by a compiler, code used to produce a web service, and files containing higher-level instructions that are executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code. [0076] The specific examples and descriptions herein are exemplary in nature and embodiments may be developed by those skilled in the art based on the material taught herein without departing from the scope of the present invention, which is limited only by the attached claims.

Claims

What is claimed is:

1. A system, comprising: a histotripsy device including: a container configured to contain an interfacing fluid, the container including a surface positionable adjacent to a skin surface of a patient; a treatment device including an array of ultrasound transducers configured to generate pulses of pressure waves that are configured to travel through the interfacing fluid and into tissue below the skin surface to induce boiling histotripsy at a focal volume; and an imaging device configured to capture a view of a three-dimensional (3D) target area of the patient; and a robotic system including: a robotic arm configured to position the histotripsy device near the patient such that the surface of the container is adjacent to the skin surface; and a positioning device coupled to a distal end of the robotic arm, the positioning device configured to move the treatment device in at least three degrees-of-freedom (DOFs) to cause the focal volume to move throughout the 3D target area to treat the 3D target area using boiling histotripsy.

2. The system of claim 1, wherein the positioning device includes a first prismatic joint configured to allow translational movement of the treatment device along a first DOF, a second prismatic joint configured to allow translational movement of the treatment device along a second DOF different from the first DOF, and a third prismatic joint configured to allow translational movement of the treatment device along a third DOF different from the first DOF and the second DOF.

3. The system of claim 2, further comprising a plurality of actuators configured to move the treatment device along the first DOF, the second DOF, and the third DOF.

4. The system of any one of claims 2-3, wherein the translational movement along the first prismatic joint is along an x-axis of a 3D space, the translational movement along the second prismatic joint is along a y-axis of the 3D space, and the translational movement along the third prismatic joint is along a z-axis of the 3D space.

5. The system of any one of claims 2-3, further comprising a rotary joint configured to allow rotational movement of the treatment device.

6. The system of any one of claims 2-3, further comprising a rotary actuator configured to rotate the imaging device.

7. The system of any one of claims 2-3, further comprising a linear actuator configured to translate the imaging device.

8. The system of claim 1, wherein the positioning device includes a delta robot including: a base; three arms, each of the three arms being coupled at a proximal end to the base and at a distal end to the treatment device; and three actuators, each of the three actuators configured to couple to a respective one of the three arms, the three actuators configured to drive movement of the three arms.

9. The system of claim 8, wherein each of the three actuators is a rotary motor that is configured to rotate an input of a rotary -to-linear transmission to cause translational movement of the proximal end of the respective arm that is coupled to that actuator.

10. The system of any one of claims 8-9, wherein the delta robot is configured to move the treatment device in the at least 3 DOFs.

11. The system of any one of claims 8-9, further comprising a rotary joint configured to allow rotational movement of the treatment device.

12. The system of any one of claims 8-9, further comprising a rotary actuator configured to rotate the imaging device.

13. The system of any one of claims 8-9, further comprising a linear actuator configured to translate the imaging device.

14. The system of any one of claims 1-13, wherein the imaging device is an ultrasound imaging device.

15. The system of claim 1, wherein the treatment device is configured to be disposed within the container such that treatment device is submerged in the interfacing fluid.

16. The system of claim 15, wherein the interfacing fluid is a degassed fluid.

17. The system of any one of claims 15-16, wherein the container and the treatment device are configured to be coupled to the robotic arm such that the robotic arm is configured to move the container with the treatment device.

18. The system of any one of claims 15-16, wherein the container includes a rigid housing configured to be attached to the distal end of the robotic arm.

19. The system of claim 18, wherein the rigid housing is a top housing, the container further including a bottom housing that is compliant and is configured to be positioned adjacent to the skin surface of the patient.

20. The system of claim 19, wherein the bottom housing is formed of clear or translucent material.

21. The system of any one of claims 18-19, wherein the container further comprises a window coupled to the surface of the container, the window being coupled to enable transmission of the pressure waves generated by the array of transducers of the treatment device.

22. The system of claim 1, wherein the imaging device is configured to be disposed within the container, the system further comprising: an actuator configured to move the imaging device into engagement with the surface of the container that is positionable adjacent to the skin surface of the patient; a force sensor configured to measure a force applied to the imaging device; and a processor configured to monitor the force applied to the imaging device to determine when the imaging device is engaged with the surface of the container and sufficiently presses against the skin surface of the patient.

23. The system of claim 22, wherein the processor is further configured to cause an actuator to move the imaging device to remove bubbles between the surface of the container and the skin surface of the patient when the container is positioned adjacent to the skin surface.

24. An apparatus, comprising: a support structure; a container configured to contain an interfacing fluid, the container including a rigid housing and a compliant housing coupled to the rigid housing, the rigid housing configured to be attached to the support structure, the complaint housing configured to be disposed adjacent to a skin surface of a patient and to deform according to a shape of the skin surface; a treatment device coupled to the support structure via a positioning device configured to move the treatment device in at least three degrees-of-freedom (DOFs), the treatment device including an array of ultrasound transducers configured to be disposed in the interfacing fluid, the array of ultrasound transducers configured to generate pulses of pressure waves that are configured to travel through the interfacing fluid and into tissue below the skin surface to induce boiling histotripsy at a focal volume; and an imaging device coupled to the support structure, the imaging device configured to capture a view of a three-dimensional (3D) target area of the patient that includes the focal volume.

25. The apparatus of claim 24, wherein the bottom housing is formed of clear or translucent material.

26. The apparatus of claim 24, further comprising a deformable material coupled between the rigid housing and the treatment device, the deformable material defining an opening through which the treatment device can extend into an interior of the container.

27. The apparatus of claim 26, further comprising a sealing rim disposed around the opening and configured to form a fluid tight seal around the treatment device to seal the interfacing fluid within the container.

28. The apparatus of claim 26, wherein the deformable material is configured to accommodate relative motion between the rigid housing and the sealing rim in response to movements of the treatment device by the positioning device.

29. The apparatus of claim 26, wherein the container further includes a window coupled to a bottom of the compliant housing and configured to enable transmission of the pressure waves generated by the array of transducers of the treatment device.

30. The apparatus of any one of claims 24-29, wherein the treatment device is configured to be moved by the positioning device in at least three translational DOFs.

31. The apparatus of any one of claims 24-29, wherein the interfacing fluid is a degassed fluid.

32. The apparatus of any one of claims 24-29, wherein the imaging device is an ultrasound imaging device.

33. The apparatus of any one of claims 24-29, wherein the container is disposable after a single use.

34. The apparatus of claim 33, wherein the container includes an identifier, and the apparatus further includes a processor that is configured to read the identifier to confirm a usage status of the container prior to enabling operation of the treatment device.