Systems, devices, and methods for non-invasive treatment of tissue using boiling histotripsy

Abstract

A method includes receiving pre-operative image data of an anatomical region of interest and capturing, using an imaging device, an intra-operative view of the anatomical region of interest. The method includes registering the pre-operative image data with the intra-operative view in a common coordinate system and determining, based on registering the pre-operative image data with the intra-operative view, a treatment path for applying boiling histotripsy to a target area in the anatomical region of interest. The method includes delivering, via a histotripsy device and according to the treatment path, ultrasound waves to the target area to induce boiling histotripsy.

Description

SYSTEMS, DEVICES, AND METHODS FOR NON-INVASIVETREATMENT OF TISSUE USING BOILING HISTOTRIPSYCross-Reference to Related Applications

[0001] This application claims priority to and benefit of 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 which is incorporated herein by reference in its 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 emulsified treatment volumes that have little remaining cellular integrity. For certain medical applications, tissue emulsification 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 targetarea (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 method includes receiving pre-operative image data of an anatomical region of interest. The method includes capturing, using an imaging device, an intraoperative view of the anatomical region of interest. The method includes registering the preoperative image data with the intra-operative view in a common coordinate system. The method includes determining, based on registering the pre-operative image data with the intra-operative view, a treatment path for applying boiling histotripsy to a target area in the anatomical region of interest. The method includes delivering, via a histotripsy device and according to the treatment path, ultrasound waves to the target area to induce boiling histotripsy.

[0007] In some embodiments, a system includes a histotripsy device. The histotripsy device includes an array of transducers configured to emit ultrasound pulses including ultrasound waves that can induce boiling histotripsy in a target area of a patient. The system includes a robotic manipulator coupled to the array of transducers and configured to move the array of transducers during a treatment procedure. The system includes a first imaging device configured to capture images of a surgical field including at least a portion of the histotripsy device and the patient. The system includes a second imaging device configured to capture intra-operative views of an anatomical region of interest within the patient including the target area, the system includes a processor operatively coupled to the histotripsy device and the robotic manipulator. The processor is configured to receive pre-operative image data of the anatomical region of interest. The processor is configured to receive, from the first imaging device, image data of the surgical field including the portion of the histotripsy device and the patient, the image data of the surgical field indicative of a position of the histotripsy device. The processor is configured to receive, from the second imaging device, an intra-operative image data of the anatomical region of interest. The processor is configured to register the pre-operative image data with the intra-operative image data in a common coordinate system. The processor is configured to register the position of the histotripsy device with the common coordinate system. The processor is configured to determine, based on the registration, a treatment path for applying boiling histotripsy to the target area. Theprocessor is configured to deliver, via the histotripsy device and according to the treatment path, ultrasound pulses to induce boiling histotripsy in the target area.

[0008] In some embodiments, a system includes a histotripsy device configured to deliver boiling histotripsy to a target area of a patient. The histotripsy device includes a set of outputting elements configured to emit ultrasound waves and a set of receiving elements configured to capture energy of the ultrasound waves that is reflected by tissue of the patient. The set of outputting elements and the set of receiving elements are arranged on a support structure in a pattern. The system includes a processor operatively coupled to the histotripsy device. The processor is configured to emit, using the set of outputting elements, a first set of ultrasound waves toward the target area. The first set of ultrasound waves are configured to pass through layers of the tissue to reach the target area. The process is configured to receive, via the set of receiving elements, energy of the first set of ultrasound waves reflected by one or more structures within the layers of tissue. The process is configured to determine, based on the energy received by the set of receiving elements, one or more parameters for operating the set of outputting elements to induce boiling histotripsy in the target area. The process is configured to emit, using the set of outputting element, a second set of ultrasound waves according to the one or more parameters such that the second set of ultrasound waves passes through the layers of tissue to induce boiling histotripsy at the target area to treat the target area.

[0009] In some embodiments, a system includes a histotripsy device configured to deliver boiling histotripsy to a target area of a patient. The histotripsy device includes at least one outputting element configured to emit ultrasound waves and at least one receiving element configured to capture energy of the ultrasound waves that is reflected by tissue of the patient. The system includes a processor operatively coupled to the histotripsy device. The processor is configured to emit, using the at least one outputting element, ultrasound waves toward the target area, ultrasound waves configured to pass through layers of the tissue to reach the target area. The processor is configured to receive, via the at least one receiving element, energy of the ultrasound waves reflected by the layers of tissue. The processor is configured to determine time and intensity information of the energy reflected by the layers of tissue. The processor is configured to identify, based on the time and intensity information, characteristics of an aberration in the anatomical region of interest. The processor is configured to determine, based on the characteristics of the aberration, one or more parameters for operating the set of outputting elements to induce boiling histotripsy in the target area. The processor is configured to emit, using the at least one outputtingelement, ultrasound waves according to the one or more parameters to induce boiling histotripsy in the target area.

[0010] In some embodiments, a method includes determining a treatment path for treating a target tissue area using boiling histotripsy. The treatment path indicates a path of a focal point of the boiling histotripsy along the target tissue area. The method includes emitting, using an array of transducers, pulses of ultrasound waves having a duty cycle of greater than about 90% toward the target tissue area. The method includes moving, while emitting, the array of transducers using a robotic manipulator coupled to the array of transducers, such that each treated point along the treatment path receives energy from the pulses of ultrasound waves having an effective duty cycle of less than about 10%.

[0011] In some embodiments, an apparatus includes a histotripsy device. The histotripsy device includes a transducer array configured to emit ultrasound waves to induce boiling histotripsy in a target area of a patient. The apparatus includes an interface coupled to and supported by the transducer array, the interface configured to include an acoustic coupling medium that can cool the transducer array and allow for transmission of the ultrasound waves from the transducer array to the patient. The apparatus includes a robotic system operatively coupled to the histotripsy device, the robotic system configured to move the transducer array and the interface to treat the target area.Brief Description of the Drawings

[0012] FIG. 1 schematically depicts a HIFU system configured to induce boiling histotripsy, according to embodiments.

[0013] FIG. 2A schematically depicts a controller of a HIFU system, according to embodiments.

[0014] FIG. 2B schematically depicts a histotripsy device of a HIFU system, according to embodiments.

[0015] FIG. 2C schematically depicts a robotic system of a HIFU system, according to embodiments.

[0016] FIG. 3A schematically depicts a configuration of a histotripsy device, operating to effect mechanical and / or thermal changes in tissue, according to embodiments.

[0017] FIG. 3B depicts a graph showing a HIFU voltage pulse, according to embodiments.

[0018] FIG. 3C schematically depicts the mechanical and / or thermal changes in tissue, in response to application of HIFU, according to embodiments.

[0019] FIG. 4 depicts a flowchart of a method for treating tissue using a HIFU system, according to embodiments.

[0020] FIG. 5A depicts an example HIFU pulsing waveform for inducing boiling histotripsy and various parameters associated with lesions formed via boiling histotripsy.

[0021] FIGS. 5B and 5C depict different focal point arrangements or paths, according to embodiments.

[0022] FIG. 6 depicts lesions formed with boiling histotripsy that have overlapping regions, according to embodiments.

[0023] FIGS. 7A-7C depict various approaches for treating a volume of tissue, according to embodiments.

[0024] FIG. 8 depicts a flowchart of a method for moving a nerve using a percutaneous device, according to embodiments.

[0025] FIGS. 9A-9B depict various percutaneous device tips, according to embodiments.

[0026] FIG. 10 depicts a flowchart of determining a treatment plan for a HIFU system, according to embodiments.

[0027] FIG. 11 depicts a workflow of determining a treatment plan for a HIFU system, according to embodiments.

[0028] FIG. 12 depicts a histotripsy device capable of supporting a biopsy device, according to embodiments.

[0029] FIG. 13 A depicts an example visualization of a biopsy feedback for use with a HIFU system, according to embodiments.

[0030] FIG. 13B depicts an example visualization of shear wave elastography measurements for providing feedback for use with a HIFU system, according to embodiments.

[0031] FIG. 14 depicts a transducer array of a histotripsy device, according to embodiments.

[0032] FIG. 15 depicts a flowchart of a method for registering and tracking one or more intraoperative devices during a HIFU treatment procedure relative to an anatomy of a patient, according to embodiments.

[0033] FIG. 16 depicts a system for registering and tracking one or more intra-operative devices during a HIFU treatment procedure relative to an anatomy of a patient, according to embodiments.

[0034] FIGS. 17 and 18 depicts different interfaces for use with a boiling histotripsy device, according to embodiments.

[0035] FIG. 19 depicts a histotripsy system, according to embodiments.

[0036] FIG. 20 depicts the back of a transducer array of the histotripsy system of FIG. 19, according to embodiments.

[0037] FIG. 21 depicts an approximation of the focal point of the transducer array of the histotripsy system of FIG. 19, according to embodiments. FIG. 22 depicts the focusing geometry of the transducer array, according to embodiments.

[0038] FIG. 23 depicts a visualization setup used with the histotripsy system of FIG. 19, according to embodiments.

[0039] FIG. 24 depicts a histotripsy device of the histotripsy system of FIG. 19, with a bladder inflated and engaging a tissue surface above a target area, according to embodiments.

[0040] FIG. 25 depicts a close-up view of a lesion pattern formed by the histotripsy device of FIG. 19, according to an embodiment.

[0041] FIG. 26 schematically depicts a transducer array of a histotripsy device, according to embodiments.

[0042] FIGS. 27A-27E depict various transducer elements of a transducer array of a histotripsy device, according to embodiments.

[0043] FIG. 28 depicts a transducer array of a histotripsy device, according to embodiments.

[0044] FIG. 29 depicts a transducer array of a histotripsy device with dimpling, according to embodiments.

[0045] FIG. 30 depicts a flow chart of a method for aberration correction, according to embodiments.

[0046] Optional components and / or elements in the figures are shown in dashed lines, and described as such in the paragraphs that follow.Detailed DescriptionI. Overview of Systems and Devices

[0047] 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., to change a direction of incidence of the ultrasound waves), e.g., by a controller and / or robotic system.

[0048] 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.

[0049] 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 bemoved 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.

[0050] 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.

[0051] 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 (e.g., tumors, etc.) in tissue regions such as the liver, kidney, pancreas, prostate, thyroid, lungs, colon, muscles, connective tissue (e.g., tendons, ligaments, collagen, etc.), eyes, heart, arteries, veins, a nerve, blood, a brain, and / or the like. In some embodiments, the histotripsy system 100 can be configured to treat endometriosis. In embodiments, the histotripsy system 100 can be configured to cut, soften, denature, join, separate, shrink, and / or expand tissue in the target tissue region. In embodiments, the histotripsy system 100 can be configured to treat cancerous tissue in combination with other therapies such as minimally invasive surgery. 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 signalsfrom 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.

[0052] 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, e.g., to generate a lesion. The focal point can be located in a target area selected for treatment. 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 point by heating up the tissue, and to interact with those bubbles to produce cavitation of the bubbles. In some embodiments, the target area can be a liver, kidney, pancreas, prostate, thyroid, lungs, colon, muscles, connective tissue (e.g., tendons, ligaments, collagen, etc.), eyes, heart, arteries, veins, a nerve, blood, a brain, and / or the like.

[0053] 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 110 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.

[0054] 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 point 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.

[0055] 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.

[0056] 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 manipulator (e.g., arm) including at least onesegment and at least one joint that can translate and / or rotate the histotripsy device 120 along or about at least one axis. For example, the manipulator can be configured to translate the histotripsy device (or transducer array of the device) about at least one axis (e.g., toward and away from a patient, left or right relative to a patient, laterally, horizontally, vertically, etc.) and rotate the histotripsy device about at least one axis (e.g., roll, pitch, yaw). 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.

[0057] 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 device 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 communicably 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. Further details of this are described with reference to FIGS. 15-16.

[0058] 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 device140. 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 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 point 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 point 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.

[0059] 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.

[0060] 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 thecontroller 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.).

[0061] 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 130, 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.

[0062] 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, the disclosure of which is incorporated herein by reference.

[0063] 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.

[0064] 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 224 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, thememory 224 stores instructions that cause processor 222 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 224 can be configured to store information regarding patients, histotripsy procedures, etc.

[0065] 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 movement control 254a, a waveform parameter control 254b, an anatomical segmentation / boundary detection 254d, procedure monitoring 254e, and adaptive feedback and support 254f. In some embodiments, the processor 252 may be configured to execute only a subset of the aforementioned functions.

[0066] The processor 252 executing transducer movement control 254a can be configured to move 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.).

[0067] 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 point of the histotripsy device to different locations according 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 point of the HIFU waves does not induce undesirable heat build-up in one or more tissue portions. Forexample, the processor 252 can be configured to move the focal point 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 point 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 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.

[0068] In some embodiments, the processor 252 executing transducer 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.

[0069] The processor 252 executing waveform parameter control 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 collectedregarding a treatment area.. In some embodiments, modifying the output can include modifying the power, power density, intensity, oscillation frequency, pulse duration, PRF, duty cycle, direction of incidence, 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 point 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.

[0070] The processor 252 executing anatomical segmentation / boundary detection 254d can be configured to generate a visual representation of the target area and / or the components of the histotripsy system based on received imaging data. The imaging data can include computerized tomography (CT) data, ultrasound imaging data, magnetic resonance imaging (MRI) data, and / or the like. The processor 252 can be configured to receive pre-operative and / or intra-operative imaging data of a patient’s anatomy, which it can use to perform anatomical segmentation of regions of interest. In some embodiments, the processor 252 can be configured to receive a preoperative image dataset that is captured using a higher resolution modality, e.g., a CT or MRI scan. Then subsequently, during a treatment procedure, the processor 252 can be configured to receive an intra-operative imaging dataset, e.g., captured using a lower resolution imaging modality such as ultrasound, and to perform segmentation, obj ect or boundary detection, and / or the like to register the two image datasets to one another. In particular, the processor 252 can be configured to perform segmentation on the two image datasets to identify features that exist across the two image dataset (e.g., anatomical features). In some embodiments, the output of the segmentation can include a point cloud of the anatomical features. The processor 252 can be configured to register the first image dataset and / or the point cloud associated therewith with the second image dataset and / or point cloud associated therewith in a common coordinate system. Registration in a common coordinate system allows for the anatomy of the patient and for the ultrasound imaging device to have known relative positions. In some embodiments, the ultrasound imaging device may be fixedly coupled to a histotripsy device such that the position of the histotripsy device may also beregistered in common coordinate system. In some embodiments, the processor 252 can be configured to generate visual representations of the patient’s anatomy and / or one or more components of the HIFU system with greater fidelity or detail, based on the registration.

[0071] Optionally, the processor 252 executing procedure monitoring 254e can be configured to monitor the procedure via an imaging device (e.g., camera, etc.) and / or other sensors. For example, the processor 252 can receive tracking data associated with at least one component of the histotripsy system (e.g., system 100). The position tracking data can include the position of the robotic system, the histotripsy device, a surgical device, an ultrasound imaging device, and / or the like. The tracking data can be captured using the imaging device, such as a camera configured to capture infrared, optical, ultraviolet, or other markers. The processor 252 can register the position tracking data with the common coordinate system. Registering the position tracking data with the common coordinate system can allow the processor 252 to monitor the operation of the histotripsy system, e.g., to confirm that the system is operating according to expected protocols. In some embodiments, the processor 252 can also generate a visual representation of the target area, including obstacles (e.g., bones, nerves), and the progress of the histotripsy treatment. The visual representation can be used to assist an operator in operating the histotripsy system or for observing the histotripsy system to ensure the histotripsy system is operating as desired.

[0072] The processor 252 executing adaptive feedback and support 254f can be configured to provide a user or an operator with feedback regarding the status of the target area (e.g., one or more characteristics or properties of the tissue in the target area) and / or the operation of the histotripsy system. For example, the processor 252 can determine the volume of liquified tissue around a nerve after boiling histotripsy has been delivered. Based on the volume of liquified tissue, and / or patient anatomy, the adaptive feedback and support 254f can provide the user with a recommendation on the type of tool that is desired for moving the nerve. As another example, the processor 252 can determine a treatment plan based on an analysis of a portion of the tissue in the target area (e.g., collected using a biopsy device). For example, the processor 252 can generate a recommendation based on the analysis. The processor 252 may be configured to receive user feedback to adjust the generated recommendation and / or the implementation of the recommendation.

[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 dataassociated 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, 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 compute device 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 210 (e.g., functionally and / or structurally similar to the histotripsy device 110 of FIG. 1), according to embodiments. As schematically illustrated, the histotripsy device 210 can be configured to engage with a patient P. The histotripsy device 220 includes, optionally, sensor(s) 222, optionally, an imaging transducer 224, an actuator 225, a treatment transducer array 226, and an interface 228. In some embodiments, the histotripsy device 210 may be coupled to a robotic system (e.g., structurally and / or functionally similar to the robotic system HO ofFIG. 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 point. In some embodiments, the sensor(s) 222 can include sensors that can measure the output of the histotripsy device 202 (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 2245 may provide a perspective view of the target area.

[0078] The actuator 225 is configured to receive an input from a user and / or a controller (e.g., structurally and / or functionally similar to the controller 150 of FIG. 1 and / or the controller 250 of FIG.2). Based on the input, the actuator 225 may be configured to activate at least one function of the histotripsy device 220. For example, when the actuator 225 is activated, the histotripsy device 220 may deliver treatment to the patient P. In some embodiments, the actuator 225 is a switch, a button, and / or the like.

[0079] 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 point to create a pulsatile wavefront of ultrasound radiation directed at the focal point. For example, the transducers of the transducer array 226 may be arranged so that waves generated by each transducer converge at the focal point. 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.

[0080] 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, 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 isconfigured 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. For example, fluid can be added to a bladder to increase a distance between he transducer array 226 and the patient P, or fluid can be removed from the bladder to decrease a distance between the transducer array 226 and the patient P. Fluid can also be removed (or allowed to leak out) as the transducer array 226 may be moved (e.g., by a robotic system) to change its focal point. 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 point 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 (e.g., fluid that has leaked out of the bladder) or lubricant that allows for the interface 228 to slide / move along the surface of the patient P. In some embodiments, the interface 228 is flexible to allow for movement of the histotripsy device relative to the patient P.

[0081] 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, and a robotic manipulator 216. 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.

[0082] 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 224 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 224 can store information in a user profile. Forexample, the user profile can include information regarding multiple procedures associated with a user. In some embodiments, the memory 224 can store information regarding the position and / or orientation of the robotic system 210.

[0083] 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 robotic manipulator 216 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 manipulator 216 according to the treatment path.

[0084] The robotic manipulator 216 can be a device configured to reposition and / or reorient the histotripsy device and / or the imaging device coupled to the robotic manipulation 216. In some embodiments, the robotic manipulator 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 rotation. In some embodiments, the robotic manipulator 216 includes an arm coupled to a histotripsy device and a separate arm coupled to an imaging device (e.g., an imaging transducer array). In some embodiments, as described in more detail below, the histotripsy device and the imaging device are coupled to an arm of a robotic manipulator 216 in fixed relation to one another. In some embodiments, the robotic manipulator 216 may include markers (e.g., dots, points, shapes, etc.) that may allow for an imaging device to track the movement of the robotic manipulator 216.

[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 transducer array 225 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 an 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 F. The focal point F may be the precise point 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.

[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 326 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 328a 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 showsHIFU 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 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, emulsified, 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.II. Methods of Treatment Planning and Delivery

[0091] FIG. 4 depicts a flowchart of a method 400 for treating tissue using a HIFU or histotripsy system (e.g., structurally and / or functionally similar to any of the HIFU systems described herein, such as the system 100 of FIG. 1), according to embodiments. In some embodiments, the method can include feedback control. For example, a processor (e.g., of controller 250 or another compute device) can be configured to monitor treatment progress or other factors during a boiling histotripsy treatment, and to control the HIFU system to continue delivering HIFU to one or more tissue portions until sufficient fractionation of tissue has been achieved. In some embodiments, the method 400 can be used to treat tissue in a liver, kidney, pancreas, prostate, thyroid, lungs, colon, muscles, connective tissue (e.g., tendons, ligaments, collagen, etc.), eyes, heart, arteries, veins, a nerve, blood, a brain, and / or the like.

[0092] At 402, the method 400 includes determining a treatment protocol for treating a target tissue volume. In some embodiments, determining the treatment protocol can involve determining a path (e.g., treatment path) through a portion of tissue (e.g., a layer or volume of tissue). The pathmay be a path along which a histotripsy system can deliver treatment to the tissue. In some embodiments, the path is determined for one or more layers (e.g., planes) of the tissue. The path can involve movement of the focal point of a transducer array of a histotripsy device (such as any of the histotripsy devices described herein) according to a predetermined trajectory, e.g., to treat multiple tissue portions. For example, for a given treatment area or volume, the treatment area can be divided into multiple portions or sections of tissue. The path can involve moving the focal point of the HIFU transducer to each of the tissue portions, and at each tissue portion, delivering HIFU waves to cause mechanical fractionation of that tissue portion.

[0093] In some embodiments, the treatment protocol can involve delivering HIFU energy to a plurality of tissue portions according to a predetermined path, and cycling back to certain tissue portions to deliver additional doses of HIFU energy. The treatment protocol can be selected to induce mechanically-fractionated lesions in each of the tissue regions with a controlled degree of thermal effect. To achieve boiling histotripsy while avoiding undesirable thermal effects, the HIFU energy being delivered to a focal point needs to have a sufficiently low duty cycle, e.g., between about 2% and about 10% or less, including all sub-ranges and values therebetween. In particular, the duty cycle can be less than about 10%, less than about 2%, or between about 1% and 2%. Conventional treatment approaches involve treating a single point or tissue portion at a time. In other words, conventional approaches include treatment pauses between applying treatment to allow for the tissue to cool to a desirable level. The treatment pauses, however, are inefficient, and increase the amount of total time of the procedure. To avoid having to turn off a transducer array for about 90% to about 98% of the time (or more) while treating a single tissue portion, the focal point of the transducer array can be moved, e.g., according to a predetermined path set by a treatment protocol. This can increase efficiency of the procedure and reduce total procedure time.

[0094] In some embodiments, determining the path can be at least partially based on a lesion width associated with treatment. As seen in FIG. 5A, the lesion width is defined as the width of a lesion formed by histotripsy. The length of the treatment plan can be defined as the sum of the widths of the total number of lesions desired to treat the target area. In some embodiments, the path can include overlapping lesions, as seen in FIG. 6. In some embodiments, the histotripsy system may be configured to deliver energy to the tissue while the focal point is in motion, thus allowing for a greater effective duty cycle, since treatment does not have to be stopped for the heated tissue to cool. For example, as seen in FIG. 5A, the voltage of the transducers of the histotripsy system alternates between an off position (e.g., between Time = 0 and Time = t_0 and between Time = t’ and Time = t_l) and an on position (e.g., between t_0 and t’ and after t_l).When the focal point is stationary and only focused on one point, the off times are greater to allow the bubble formed by histotripsy to cool. When the focal point is moving, the off times can be decreased as the cooling time may not be desirable, thus increasing the effective duty cycle of treatment and saving the physician and the patient time.

[0095] In some embodiments, HIFU energy may need to be delivered to a portion of tissue more than once. For example, as seen in FIG. 5B, the path may involve moving the focal point in a loop. The loop may repeat any number of times (e.g., one time, two times, three times, four times, five times, 10 times, 15 times, 50 times, etc.), such that each tissue portion along the loop can receive HIFU energy multiple times, until those portions are sufficiently treated (e.g., mechanically fractionated). In some embodiments, the path can be comprised of segmented smaller loops to treat specific areas of a larger region, as seen in FIG. 5C. The smaller loops may be more optimal for treating various types of tissue and / or for specific applications.

[0096] Treatment paths or trajectories as described herein can involve different approaches or types of movement. In some embodiments, the movement of the focal point can be at a constant velocity or rate, without pausing or stopping at any one tissue portion. In some embodiments, the movement of the focal point can involve accelerations and decelerations, such as fast movements to each tissue portion, followed by deceleration while the focal point is maintained at the tissue portion, and then acceleration as the focal point is moved to another tissue portion. In some embodiments, the movement of the focal point can be a sweeping approach, whereby the focal point is swept from one tissue portion to adjacent tissue portions. FIG. 7A depicts an example of the sweeping approach. As shown in FIG. 7A, the sweeping approach can include continuously sweeping the focal point across the tissue, so that treated tissue cools while new tissue is being treated. In some embodiments, the movement of the focal point can involve a target hopping approach, whereby the focal point is moved to a plurality of points or positions in a target array of a tissue region T. FIG. 7B depicts an example target array, according to embodiments. A path can be determined that delivers treatment to each point of the target array. FIG. 7C shows that the target hopping approach can be further implemented to fill in any gaps between treated points, e.g., to ensure that the entire target area is treated. For example, multiple passes of delivering energy, each represented by a different color in FIG. 7C, can be used to fill in the entire area of a tissue region. In some embodiments, this denser treatment may not be necessary, and a sparser treatment, such as the one shown in FIG. 7B, may already be effective at treating the target tissue. In some embodiments, the determined path can involve multiple types of movement. For example, a portion of the tissue can be treated using a target hopping approach, and another portion can betreated using a sweeping approach. Regardless of the approach, each can be configured to maintain the duty cycle of the HIFU energy delivered to any one tissue portion to desirable ranges, e.g., between about 2% and about 10% or less, including all sub-ranges and values therebetween.

[0097] The sweeping and target hopping approaches described above may each have different advantages. For example, the sweeping approach, as shown in FIG. 7A, may move the focal point smoothly through a path, which can leverage the heating of a region, allowing for smooth application of heat. This smooth application of heat can create a smooth path of ablation, rather than many separate lesions. The sweeping approach can also represent a more simplified mapping of a treatment area. The target-hopping approach may allow for faster overall heat diffusion, which may enable faster treatment. Moreover, if a sparser target-hopping approach were used, e.g., such as that depicted in FIG. 7B, then such can further reduce the timing needed for treating a larger volume of tissue.

[0098] In some embodiments, 402 can be optional, as the treatment protocol or path can be set by a user or pre-stored in memory. In such instances, a processor (e.g., of controller 250 or another compute device) con be configured to access and implement the treatment protocol.

[0099] At 404, the method 400 includes setting a duty cycle and / or PRF of a histotripsy device of the histotripsy system. In some embodiments, the duty cycle and / or pulse repetition rate can be set based on the treatment path or trajectory, e.g., determined at 402. For example, the histotripsy system can be configured to activate the transducer array of a histotripsy device at higher duty cycles or PRF than those associated with boiling histotripsy, when the transducer array is being moved to deliver HIFU energy to multiple tissue portions (e.g., manually or by a robotic system). When the transducer array is being moved, the duty cycle that is effectively experienced at each tissue portion can remain within boiling histotripsy ranges, even if the duty cycle or PRF of the transducer array is much higher. Therefore, at 404, the duty cycle and / or PRF of a histotripsy system can be set based on parameters associated with the movement of the transducer and its treatment path (e.g., speed of movement, acceleration / deceleration, length of path, etc.). In some embodiments, the duty cycle and / or the PRF can be determined based on the characteristics of the tissue region to be treated (e.g., size, type of tissue, location within anatomy, etc.). In some embodiments, the duty cycle and / or PRF can change (e.g., be variable) along a path or during a treatment. In some embodiments, 404 may be optional, e.g., when the duty cycle and / or the PRF are predetermined.

[0100] At 406, the method 400 includes delivering energy, using the histotripsy device, to each focal point along the path while maintaining effective duty cycle at each focal point in the boilinghistotripsy range. In some embodiments, the histotripsy device is moved to each focal point manually. In some embodiments, the histotripsy device is moved to each focal point via a robotic system (e.g., robotic system 210) coupled to the histotripsy device. In some embodiments, the robotic system can be controlled by an operator, e.g., using an input device. In some embodiments, the robotic system operates automatically. The robotic system can be configured to receive the treatment path defining the desired movements of the focal point, and to implement movements of one or more components of the robotic system (e.g., one or more joints and / or links of the robotic system) to move the histotripsy device to delivery HIFU energy to each focal point along the path. The histotripsy device is moved such that the effective duty cycle experienced at each focal point is in the boiling histotripsy range. The operational parameters of the robotic system can be determined based on the path length of the histotripsy device. As shown in FIG. 5A, the length of the path (Lpath) and the length of the lesion (Liesion) can determine a number of lesions (Numlesions'). In particular, Numiesions can equal Lpath divided by Liesion. The robotic system can be configured to move the transducer array of the histotripsy device at a set velocity Vo and / or acceleration arobot. When defined in relation to the path length Lpath)

[0101] When the movement of the transducer array is at a constant velocity, i.e., Vo > 0 m / sec constant velocity, then Lpath simplifies to:

[0102] Therefore, the duration that the robotic system controls the movement of the transducer array, and the velocity and / or acceleration at which the robotic system moves the transducer array are related to the path length Lpath).

[0103] At 408, the method 400 optionally includes determining if the tissue has received a desired amount of HIFU energy, e.g., to cause the tissue to mechanically fractionate. Determining if the tissue has received the desired amount of energy can be based on known operational parameters, including, for example, the amount of energy absorbed by the tissue, total time treated, number of times treated, and / or the like. The histotripsy system can determine whether the amount of energy delivered is greater than a predefined threshold. In some embodiments, determining if the tissue has received the desired amount of energy can involve capturing information about the tissue state (e.g., imaging data and / or other sensor data), and analyzing that information to determine whether the tissue has mechanically fractionated. If the tissue is determined to not havereceived a desired amount of energy, the method 400 continues to 410. At 410, the method 400 includes cycling back to one or more tissue portions and repeating delivery of energy while maintaining effective duty cycle at each tissue portion in the boiling histotripsy range. In some embodiments, the histotripsy device only delivers energy to portions of the tissue that are determined to not have received a desired amount of energy. In some embodiments, the histotripsy device delivers treatment to each tissue portion along the path until a desired amount of energy has been received throughout the tissue region. If the tissue is determined to have received a desired amount of energy, the method 400 continues to 412.

[0104] At 412, the method 400 optionally includes determining if another potion of tissue needs to be treated. Determining whether to treat another portion of tissue can include determining if the entirety of the region of interest has been treated or if there is another portion of tissue where treatment is necessary. If additional treatment is desired, the method 400 returns to 402 to determine a new path. If additional treatment is not desired, the method 400 ends.

[0105] With the movement of the transducer array allowing for increased duty cycle, the duty cycle of the transducer array may be able to approach 100%. However, given practical limitations of transducer designs and overheating concerns, the duty cycle of the transducer array may be limited to lower values. In some embodiments, active cooling management may be used to cool the transducers. For example, fluid within an interface (e.g., interface 228, such as a bladder) can be used to actively cool the transducers. Alternatively, fluid can be placed on a backside of the transducers and used to cool the transducers, Cooling fans or other types of active cooling devices can be used to further cool the transducer array during operation. In some embodiments, a temperature sensor can be used to monitor the temperature of the transducers and / or cooling fluid, and when such temperatures reach certain thresholds, the histotripsy system may be configured to pause operation (e.g., stop delivery of HIFU pulses to the transducer array) and / or implement additional active cooling (e.g., by replacing the cooling fluid with new fluid, by activating a fan or other active cooling mechanism, by delivering additional fluid to other sides of the transducer, etc.). In some embodiments, a quadrant or divided bladder bag can be used in conjunction with detecting when the cooling fluid has reached a threshold, such that the system cn reposition to another quadrant or bag to continue delivering HIFU energy. In some embodiments, the transducer array can also be comprised of multiple transducer heads that can rotate to swap out transducers that have overheated.

[0106] FIG. 8 depicts a flowchart of a method 800 for moving a nerve using a percutaneous tool, according to embodiments. During certain procedures where boiling histotripsy is applied,such as to herniated disks in the spine, nerves can impinge HIFU reaching and treating the bulging disk. The method 800 depicts steps for identifying and using tools to use to move a nerve.

[0107] At 802, the method 800 includes delivering boiling histotripsy to a volume of tissue around a nerve. The boiling histotripsy can be delivered to the tissue by a histotripsy system, such as the system 100 of FIG. 1. At 804, the method 800 includes determining a volume of liquified tissue around the nerve after the boiling histotripsy is delivered to the volume of tissue. Determining the volume of liquified tissue can include imaging the tissue, measuring the size and / or shape of the liquified tissue, determining the amount of energy delivered to the tissue, and / or the like.

[0108] At 806, the method 800 includes determining, based on the size of the volume of liquified tissue and / or patient anatomy, a work volume. The work volume is associated with the volume of liquified tissue and / or patient anatomy that can be used when moving the nerve. At 808, the method 800 includes determining, based on the work volume, a percutaneous tool tip that can fit within the work volume and is capable of moving the nerve. Determining the percutaneous tool tip can be based on the size of the work volume available, the location of the nerve, the size of the nerve, and / or the like.

[0109] The percutaneous tool can be configured to move the nerve. The percutaneous tool can be manually operated or can be coupled to a robotic system, such as the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2C. Various example of percutaneous tool tips can be seen in FIG. 9A. In some embodiments, the percutaneous tool tip can be a similar to a needle tip for insertion. In some embodiments, the percutaneous tool tip can be a blunt tip for moving the nerve atraumatically. In some embodiments, the percutaneous tool tip can be a nitinol tip that, when heated by boiling histotripsy, can be induced to shape change. For example, a percutaneous tool tip changing shape is shown in FIG. 9B. In some embodiments, the percutaneous tool tip is a nitinol strut that can be bonded to bone with acoustic cross-linking epoxy tips such that the strut can be tacked in place and bonded to fuse the strut to the bone using boiling histotripsy. In some embodiments, boiling histotripsy can be used to form tunnels for the nitinol to expand into. In some embodiments, an inflatable balloon membrane can be used with boiling histotripsy applied to it to cause expansion to move the nerve. After determining the percutaneous tool tip that can fit within the work volume in 808, the nerve is moved. The percutaneous tool can be moved by a user manually or can be controlled by the robotic system to move the nerve.

[0110] At 810, the method 810 includes imaging, after moving the nerve, a volume of tissue to confirm whether a procedure can proceed. Imaging data captured of the volume of tissue, afterthe nerve has been moved, can be used to determine whether the procedure can safely proceed. In some embodiments, the imaging data can be presented to a user (e.g., a surgeon) for viewing and determining of whether the procedure can proceed. In some embodiments, the imaging data can be analyzed by a processor (e.g., of controller 250 or another compute device). In some embodiments, if the nerve has not been move to a suitable location (e.g., out of the way of a procedure), the method 800 can repeat to safely move the nerve again.

[0111] FIG. 10 depicts a flowchart of a method 1000 of determining a treatment plan for a HIFU system, according to embodiments. The method 1000 can be used during treatment of a patient to perform checks of the tissue in a target region to provide a surgeon with information on the progress of the treatment so that adjustments and decisions can be made accordingly. The method 1000 may involve the operation of a histotripsy system (e.g., functionally and / or structurally similar to the system 100 of FIG. 1) and a needle or biopsy device. In embodiments, the method 1000 can be performed by a processor (e.g., of controller 250 or another compute device).

[0112] At 1002, the method 1000 optionally includes positioning an end effector of a treatment device over a target area. In some embodiments, the treatment device is 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 the end effector can be a transducer array with an interface, as described with reference to FIG. 2B. Positioning the end effector can include controlling a robotic system (e.g., structurally and / or functionally similar to the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2C) to position the treatment device such that the treatment device is configured to direct treatment to the target area. In some embodiments, 1002 can be manually performed by a user (e.g., a surgeon), and therefore is shown as optional in FIG. 10.

[0113] At 1004, the method 10000 includes determining, using a sensing device, at least one characteristic associated with the tissue in the target area. In some embodiments, the at least one characteristic can include a scan of the target area. In some embodiments, the sensing device is an ultrasound imaging device. At 1006, the method 1000 includes treating, by a histotripsy device, a portion of the tissue in the target area. Treating the portion of the tissue in the target area can include delivering boiling histotripsy to the tissue. The portion of the tissue is treated until the tissue is treated to a desirable level. For example, the desirable level can be a level of treatment that allows for extraction.

[0114] At 1008, the method 1000 includes extracting, using an extraction tool, the portion of the tissue in the target area. The extraction tool can be a needle or other tool (e.g., other biopsydevice) that can be configured to extract a small amount of cellular debris from the target area. In some embodiments, the extraction tool can be integrated with the histotripsy system, while in other embodiments, the extraction tool can be a separate tool or instrument. At 1010, the method 1000 includes determining, based on the extracted portion of the tissue, a treatment plan or protocol. Determining the treatment plan can include doing a biopsy of the portion of tissue to aid the surgeon in determining the treatment plan. The treatment plan can specify parameters of operating the treatment device (e.g., parameters of operating the transducer array to generate HIFU waves) and / or receiving treatments. For example, the treatment plan can specify the power being applied, the spacing between treatments, input parameters, voltage, oscillation frequency, PRF, duty cycle, etc. In some embodiments, the treatment plan can include a diagnosis of the target area (e.g., cancer).

[0115] FIG. 11 depicts a workflow 1100 for determining a treatment plan for a HIFU system, according to embodiments. The workflow 1100 depicts how a surgeon S interacts with a system 1102 (e.g., structurally and / or functionally similar to the system 100 of FIG. 1). Determining a treatment plan can allow for a medical professional (e.g., physician, the surgeon S, etc.) to gain insight in a procedure during the procedure to make informed decisions about the operation. The workflow 1100 allows for histotripsy to be a diagnostic tool in addition to treatment, which can result in increased patient satisfaction, and more personalized care for a patient. In some embodiments, certain portions of the workflow 1100 can be optional depending on the type of procedure, medical professional preference, and / or the like.

[0116] At 1106, the workflow 1100 includes the surgeon S preparing a patient for a procedure. Preparing the patient can include positioning the patient in a procedure room. In some embodiments, the surgeon S can apply a preparative substance, such as an ultrasound gel to a region of interest of the patient that is desired to be scanned. In some embodiments, the surgeon S can prepare the system 1102 for the procedure. For example, the surgeon S can adjust system 1102 setting and / or the like.

[0117] At 1107, the workflow 1100 includes the system 1102 scanning the patient. Scanning the patient can include using an imaging device (e.g., structurally and / or functionally similar to the imaging device 140 of FIG. 1) to generate image data of the region of interest. In some embodiments, multiple portions of the patient can be scanned. In some embodiments, the patient can be scanned using one or more imaging method, such as ultrasound, CT, and / or the like. After generating the image data of the region of interest, the system 1102 can generate a visualization (e.g., model) of the image data. For example, the visualization can include a user interface for thesurgeon S to alter the visualization (e.g., zoom, reorient, etc.). In some embodiments, checking the tissue can include classifying or labeling the tissue. For example, the size of the tissue can be labeled, the type (e.g., tumor, etc.) can be classified, the tissue can be labeled, and / or the like.

[0118] At 1108, the workflow 1100 includes the surgeon S visualizing the anatomy of the patient. The surgeon S can determine what portion of the region of interest is desirable to inspect and / or treat. At 1110, the workflow 1100 includes the surgeon S selecting a target (e.g., tissue region), based on the surgeon S visualizing the anatomy of the patient. In some embodiments, the target can include one or more targets. In some embodiments, the surgeon can determine features of the target, such as the size of the target, the shape of the target, and / or the like. In some embodiments, the surgeon S can select the target on the model of the anatomy.

[0119] At 1111, the workflow 1100 includes the system 1102 positioning a needle guide (or guide for a biopsy device). The needle guide is a guide configured to allow a surgeon to align a needle or other biopsy device to engage the target. In some embodiments, the needle guide can be coupled to a robotic system (e.g., functionally and / or structurally similar to the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2C). In some embodiments, the needle guide can be positioned manually or based on an input from the surgeon S. In some embodiments, the needle guide may be positioned by the robotic system automatically. For example, after the surgeon S selects the target on the model, the robotic system can move the needle guide into position. In some embodiments, the needle guide is positioned so that it aligns with the focal point of a histotripsy device of the system 1102.

[0120] At 1112, the workflow 1100 includes the surgeon S inserting the needle or other biopsy device. The surgeon S can insert the needle via the needle guide. In some embodiments, the surgeon S inserts the needle manually. In some embodiments, the needle is coupled to a robotic system. In some embodiments, inserting the needle includes the surgeon S operating or commanding the robotic system to insert the needle. The needle is inserted into the target such that the needle engages the tissue in the target. In some embodiments, the needle can be another device, such as a sensor, guidewire, and / or the like. In some embodiments, the needle can be inserted to a predetermined depth.

[0121] At 1113, the workflow 1100 includes the system 1102 checking the tissue. In some embodiments, the needle can be configured to sense characteristics (e.g., stiffness, electrical signals, toughness, elasticity, water content, conductivity, etc.) of the tissue. In some embodiments, checking the tissue can additionally include ultrasound to image the tissue. For example, checking the tissue can include determining stiffness and / or boundaries of the tissue using shear waveelastography. In some embodiments, the surgeon S can view the results of checking the tissue using a visualization. As seen in FIG. 13B, an example visualization of shear wave elastography measurements for providing feedback for use with a HIFU system is shown. In some embodiments, the shear wave elastography measurements can be generated by an imaging device, such as any of the imaging devices described herein. In some embodiments, visualizations other than shear wave elastography may be generated to provide feedback. As seen in FIG. 13B, the visualization can include the volume of the mass, a suggested treatment time, labeled portions of the tissue, location in a body, and information regarding the visualization.

[0122] At 1114, the workflow 1100 includes the surgeon S confirming a starting position. Based on the data generated when checking the tissue in 1113, the surgeon S can determine whether the needle has engaged the target area, allowing the surgeon S to confirm if the position of the histotripsy system is aligned with a portion of tissue that is desirable to be treated and / or analyzed. If the surgeon S determines that the current position of the histotripsy device is not in a desirable position, the surgeon S can move the histotripsy device to a new position. In some embodiments, the workflow 1100 can return to 1111 to position the needle to check if the new position is desirable by repeating 1111, 1112, 1113, and returning to 1114.

[0123] At 1115, the workflow 1100 includes the system 1102 applying treatment. Applying treatment can include applying boiling histotripsy to the target by the histotripsy device of the system 1102 (e.g., structurally and / or functionally similar to system 100 and / or other HIFU or histotripsy systems described herein). In some embodiments, the treatment can be determined based on the information (e.g., data, etc.) obtained in 1107 and / or 1113. For example, the treatment time, treatment path, histotripsy device settings, and / or the like can be determined based on the information.

[0124] At 1116, the workflow 1100 includes the surgeon S beginning a cell biopsy. In some embodiments, 1116 can occur simultaneously with 1115. For example, during 1116 a needle can be used to extract a portion of cellular debris from the tissue liquified by boiling histotripsy in 1115. In some embodiments, only enough treatment is applied to the target so that a portion can be removed for biopsy. In some embodiments, the workflow 1116 returns to 1110 to repeat the workflow 1100 for additional targets. In some embodiments, 1116 is optional.

[0125] At 1117, the workflow 1100 includes the system 1102 completing the biopsy. Completing the biopsy can include determining what type of tissue is in the target. In some embodiments, the output of the biopsy can be generated by the surgeon S analyzing the extracted tissue. In some embodiments, the output of the biopsy can be generated by the system 1102analyzing the tissue. In some embodiments, the output of the biopsy can indicate a likelihood that the tissue is cancerous. In some embodiments, 1117 is optional. For example, when 1116 is not included in the workflow 1100, 1117 is also not included.

[0126] FIG. 13 A depicts an example visualization of a biopsy feedback for use with a HIFU system. The visualization (e.g., image, scan, etc.) can include biopsied tissues, results of the biopsy, and a recommendation for adapting treatment. The results of the biopsy include a percentage that the tissue is cancerous. In some embodiments, the results can include a recommendation for treatment. In some embodiments, the results can include information regarding the composition of the tissue. In some embodiments, the recommendation can include an option to extend the target. The feedback included in the visualization can be used to determine additional treatment steps or to change / augment a procedure during the procedure. For example, in some embodiments, the biopsy feedback can be used to adjust one or more parameters of operating a histotripsy system, e.g., to deliver boiling histotripsy.

[0127] At 1118, the workflow 1100 includes the surgeon S completing the diagnosis and / or treatment. Completing the diagnosis can include determining if additional diagnosis is needed. For example, if it is desirable for another potion of tissue to be biopsied and / or analyze. As another example, it may be desirable to obtain additional information regarding the tissue. If it is determined that additional information and / or additional diagnosis is needed, additional biopsy or analysis (e.g., scanning, imaging, etc.) can be executed on the tissue. Completing the treatment can include applying boiling histotripsy to the tissue until the treatment is completed. In some embodiments, the remainder of the treatment can include modification based on the results of the biopsy. For example, if the biopsy determines the tissue is cancerous, the treatment can be configured to apply boiling histotripsy to the area of the tissue determined to be cancerous.III. Visualization and Tracking

[0128] FIG. 15 depicts a flowchart of a method 1500 for registering and tracking one or more intraoperative devices during a HIFU treatment procedure relative to an anatomy of a patient, according to embodiments. The method 1500 can be executed with a system, such as the system 100 of FIG. 1. The method 1500 can provide a medical professional with information (e.g., visualization, etc.) that can guide the medical professional during the operation or allow the medical professional to monitor the operation. The method 1500 allows for an increase in precision, which may be beneficial during operations such as spinal procedures. In some embodiments, the inputs and / or the outputs of the method 1500 can be monitored and / or controlled by a user via an application on a user device. Registration during the method 1500 allows forvarious devices used during the HIFU treatment procedure to be tracked in the same coordinate system to allow for movement control and visualization of the devices relative to the anatomy.

[0129] At 1502, the method 1500 includes obtaining, using one or more imaging device, preoperative image data of an anatomical region of interest. In some embodiments, the image data includes a 3 -dimensional scan of the anatomical region of interest. In some embodiments, the imaging device is a CT device, an MRI device, and / or the like. In some embodiments, the image data can include image data from more than one device.

[0130] At 1504, the method 1500 includes performing segmentation of the image data to identify key anatomical features. Segmentation can include partitioning the image data into image segments. In some embodiments, segmentation can include segmenting the image data into slices. The image segments are then analyzed to identify key anatomical features. In some embodiments, segmentation and / or identifying key anatomical features can include using an artificial intelligence model. In some embodiments, the key anatomical features can include anatomical features such as tissue structures (e.g., soft tissue structures such as organs, fatty tissue, etc., or bones), tumors, and / or the like. At 1506, the method 1500 includes generating a point cloud of the anatomical region of interest. In some embodiments, the point cloud is generated by segmenting each slice from the segmentation in 1504 and stacking the segmentations into a point cloud. In some embodiments, the point cloud is a representation of the bone of the patient in and / or around the anatomical region of interest. In some embodiments, the point cloud can include a representation of a tumor and / or similar tissue.

[0131] At 1508, the method 1500 includes capturing, using an ultrasound imaging device (e.g., functionally and / or structurally similar to the imaging device 140 of FIG. 1 and / or the imaging transducer 224 of FIG. 2B), an intra-operative (e.g., during an operation, during a procedure, etc.) view of the anatomical region of interest. In some embodiments, the ultrasound imaging device can be coupled to a robotic system (e.g., functionally and / or structurally similar to the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2C). The ultrasound imaging device can be used to track the anatomical region of interest during the operation. In some embodiments, the pre-operative image data may be higher resolution than the intra-operative view.

[0132] At 1510, the method 1500 includes registering the pre-operative image data (and / or the point cloud) with the intra-operative view of the anatomical region of interest in a common coordinate system. Registration in a common coordinate system allows for the higher resolution pre-operative image data to be used during the procedure so that a surgeon can accurately visualize the region of interest based on the lower quality intra-operative view. In some embodiments,registration can include transforming and / or translating the coordinates frames of the pre-operative image data and the intra-operative view. In some embodiments, registration can include generating a point cloud for the intra-operative view prior to registration. In some embodiments, registration can include using a probabilistic coherent point drift. For example, the coherent point drift can be used to register the point cloud associated with to the pre-operative image data and the point cloud associated with the intra-operative view. In some embodiments, registration can additionally include determining an error estimation indicating an accuracy of the registration. Determining an error estimation can include generating several visualization to assess the quality of the registration.

[0133] At 1512, the method 1500 optionally includes obtaining tracking data of a position of one or more intra-operative devices (e.g., robotic device, histotripsy device, surgical device, ultrasound imaging device, probe, etc.). In some embodiments, the tracking data can be generating by an imaging device (e.g., structurally and / or functionally similar to the imaging device 140 of FIG. 1), or be generated based on image data captured by an imaging device. In some embodiments, the imaging device can be a camera that can capture optical, infrared, ultraviolet, or other objects or markers in an environment. The imaging device can be oriented to observe the function of a histotripsy system in an operating room, e.g., a surgical field including the histotripsy device (or portion thereof) and a patient in the operating room. The one or more intra-operative devices can include one or more markers (e.g., fiducial markers) that the imaging device utilizes to track the one or more intra-operative devices. The image data captured by the imaging device can be used to determine or track a position of the intra-operative device(s). In some embodiments, obtaining tracking data may include a calibration step. For example, the tracking of the intraoperative devices can be based on a tracking algorithm, e.g., an algorithm that is configured to identify one or more markers associated with an intra-operative device in image data (e.g., via segmentation, object recognition, etc.) and to determine a position of the intra-operative device based on position(s) of the one or more markers. The calibration step can include the one or more intra-operative devices posing in a series of poses that can be recorded by the imaging device. At 1514, the method 1500 optionally includes registering the position of the intra-operative devices with the common coordinate system. Registration of the position of the intra-operative devices can include registering the tracking data to the common coordinate system. In some embodiments, the registration in 1514 can be the same or similar process to the registration described in reference to 1510. Registration can be used to generate a visual representation of the anatomical region of interest, as described below. Registration of an intra-operative view to pre-operative scans can also enable intra-operative treatment planning. For example, a compute device as described herein canbe used to determine, based on the registration of the pre-operative image data with the intraoperative view, a treatment path for applying boiling histotripsy to a target area, and then cause a boiling histotripsy device as described herein to generate and direct ultrasound waves toward the target area to induce boiling histotripsy.

[0134] At 1516, the method 1500 includes generating a visual representation of the anatomical region of interest and / or one or more intra-operative devices. The visual representation can include a 3-dimensional mapping of the operation, including the anatomical region of interest and / or the intra-operative devices. The visual representation allows the surgeon to observe the procedure remotely and / or monitor the position of the intra-operative devices during the operation. In some embodiments, the visual representation can be monitored on a display. In some embodiments, the visual representation can include a position of a probe, distance from probe to selected target, position of the robotic system, and / or the like. In some embodiments, the visual representation can include a live ultrasound of the procedure. In some embodiments, the visualization can display an error estimation indicating an overall accuracy of the visual representation.

[0135] FIG. 16 depicts a system 1600 (e.g., functionally and / or structurally similar to the system 100 of FIG. 1) for registering and tracking one or more intra-operative devices during a HIFU treatment procedure relative to an anatomy of a patient, according to embodiments. In some embodiments, the system 1600 can be utilized to execute a method for generating the visual representation, such as the method 1500 of FIG. 15. The system 1600 includes a robotic system 1610 (e.g., structurally and / or functionally similar to the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2C) coupled to a histotripsy devicel620 (e.g., structurally and / or functionally similar to the histotripsy device 120 of FIG. 1 and / or the transducer device 220 of FIG. 2B). The robotic system 1610 is configured to position the histotripsy device 1620 above tissue T that includes an anatomical region of interest. The histotripsy device 1620 is configured to deliver boiling histotripsy to the tissue T. The histotripsy device 1620 includes an imaging transducer configured to image the tissue T. An output 1690 depicts an example visualization of the tissue T based on the output from the imaging transducer. The visualization can be an output of a registered visualization, such as described in reference to FIG. 15. The system 1600 includes a probe 1670 that is configured to engage the tissue T. The probe 1670 can be configured to measure characteristics of the tissue T and / or to remove a portion of the tissue T for a biopsy.

[0136] The system 1600 further includes an imaging device 1640 (e.g., structurally and / or functionally similar to the imaging device 140 of FIG. 1). The imaging device is configured to observe markers 1641 (e.g., fiducial markers) on the probe 1670 and / or on the robotic system 1610and / or the histotripsy device 1620. The markers provide a point that the imaging system 1640 can use to track the movement of the probe 1670, the robotic system 1610, and / or the histotripsy device 1620. The imaging system 1640 generates tracking data based on the positions of the probe 1670, the robotic system 1610, and / or the histotripsy device 1620. In some embodiments, the imaging device 1640 can include more than one camera to allow for the tracking data to be 3 -dimensional. The tracking data can be used to register the position of the probe 1670, the robotic system 1610, and / or the histotripsy device 1620 to a common coordinate frame with the tissue T and / or the histotripsy system 1620.IV. Example Embodiments of Histotripsy Systems and Components

[0137] FIG. 12 depicts a histotripsy system 1200 (e.g., structurally and / or functionally similar to the system 100 of FIG. 1) capable of supporting a biopsy device (e.g., examination device), according to embodiments. The histotripsy system 1200 includes a robotic system 1210 (e.g., functionally and / or structurally similar to the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2) coupled to a histotripsy device 1220 (e.g., functionally and / or structurally similar to the histotripsy device 120 of FIG. 1 and / or the histotripsy device 220 of FIG. 2). The histotripsy system 1200 additionally includes an examination device 1270 (e.g., structurally and / or functionally similar to other examination devices and / or biopsy devices described herein). The histotripsy system 1200 is engaging a partially liquified portion of tissue T of the patient P.

[0138] The histotripsy device 1220 supports the examination device 1270 via guides 1221 that are configured to allow for the examination device 1270 to engage the tissue liquified by the histotripsy device. The guide 1221 can be positioned and / or shaped such that the examination device 1270, when inserted into the guide 1221, can engage the tissue T at the focal point of the histotripsy device 1220. The examination device 1270 can be configured to measure characteristics of a nerve (e.g., electrical stimulation, electrical signals, etc.), characteristics of a tumor (e.g., mechanical stiffness, tumor etc.), general characteristics of the tissue (e.g., cellular composition, water content, conductivity, etc.).

[0139] FIG. 14 depicts a transducer array 1446 (e.g., structurally and / or functionally similar to the transducer array 246 of FIG. 2B) of a histotripsy device, such as any of the histotripsy devices described herein, according to embodiments. FIG. 14 depicts a side view of the transducer array 1446 such that the transducers 1446a can be seen. The transducers 1446a are covered with a coating 1446b. In some embodiments, the coating 1446b includes a hydrophilic coating. The hydrophilic coating can allow for bubbles formed during treatment to travel along the coating 1446b to an opening 1446c to allow for the bubbles to escape. Allowing the bubbles to escape isadvantageous, as the bubbles can damage the transducer array 1446 or can affect the propagation of energy from the transducers 1446a. FIG. 14 additionally shows the shape of the transducer array 1446 that allows for the transducer array 1446 to focus energy onto a focal point. In some embodiments, the shape of the transducer array 1446 can be modified to change the distance from the transducer array 1446 to the focal point.

[0140] Referring generally to FIGS. 17-18, different interfaces for use with a boiling histotripsy device are shown, according to embodiments. The interfaces allow for energy to be delivery to the tissue of the patient desirably. In some embodiments, the interface can be chosen based on a characteristic of the procedure (e.g., procedure type, target area size, etc.) and / or of the patient (e.g., patient anatomy, etc.)

[0141] FIG. 17 depicts a histotripsy device 1720 (e.g., functionally and / or structurally similar to the histotripsy device 120 of FIG. 1 and / or the transducer device 220 of FIG. 2B) coupled to a robotic system 1710 (e.g., functionally and / or structurally similar to the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2C) engaging tissue T of a patient, according to embodiments. The histotripsy device 1720 is configured to allow for acoustic coupling so that energy from the histotripsy device 1720 can be propagated to the tissue T.

[0142] The histotripsy device 1720 includes a transducer array 1726 (e.g., functionally and / or structurally similar to the transducer array 226 of FIG. 2B), an imaging transducer 1724 (e.g., functionally and / or structurally similar to the imaging transducer 224 of FIG. 2B), an interface 1728 (e.g., functionally and / or structurally similar to the interface 228 of FIG. 2B), an inlet 1721, and an outlet 1729. The imaging transducer 1724 is colinear to the transducer array 1726 which is coupled to the interface 1728. The interface 1728 engages the patient. The histotripsy device 1720 is configured to apply boiling histotripsy to the tissue T of the patient. The transducer array 1726 is coupled to the inlet 1721. The inlet 1721 is configured to deliver a cooling fluid (e.g., water) to the transducer array 1726 for cooling the transducer array 1726. The inlet 1721 may be coupled to a cooling system, a fluid reservoir, or the like to allow for the transducer array 1726 to be cooled. The outlet 1729 is configured to allow for bubbles formed during histotripsy to escape from the surface of the transducer array 1726 as described in reference to FIG. 14.

[0143] The interface 1728 is filled with a fluid configured to operate as a medium for energy from the transducer array 1726 to engage the tissue T. In some embodiments, the fluid is deionized and / or degassed water. The interface 1728 is a flexible membrane that can create a seal with the skin of the patient while allowing for movement of the robotic system 1710. In some embodiments, the skin of the patient may be prepared (e.g., shaved, have gel applied, etc.) prior to forming a sealwith the interface 1728. In some embodiments, a partial vacuum may be pulled in the interface 1728, as described in reference to FIG. 18.

[0144] FIG. 18 depicts an interface 1828 (e.g., structurally and / or functionally similar to the interface 228 of FIG. 2B and / or the interface 1728 of FIG. 17), according to embodiments. The interface 1828 is fluidly coupled to a fluid reservoir 1828a and an outlet 1828b. The fluid reservoir 1828a allows for the fluid from the interface 1828 to be drawn out so that the interface 1828 can be relocated. The outlet is configured to draw out air / or fluid from the interface 1828 to induce a partial vacuum between the interface 1828 and a patient.

[0145] Referring generally to FIGS. 19-24, a histotripsy system 1900 (e.g., functionally and / or structurally similar to the system 100 of FIG. 1). The histotripsy system 1900 is configured for testing and / or demonstration. The histotripsy system 1900 includes a robotic system 1910 (e.g., functionally and / or structurally similar to the robotic system 110 of FIG. 1 and / or the robotic system 210 of FIG. 2C), a histotripsy device 1920 (e.g., functionally and / or structurally similar to the histotripsy device 120 of FIG. 1 and / or the transducer device 220 of FIG. 2), and an imaging device 1940 (e.g., functionally and / or structurally similar to the imaging device 140 of FIG. 1).

[0146] FIG. 19 depicts the histotripsy system 1900, according to embodiments. A seen in FIG. 19, the histotripsy device 1920 is fixedly coupled to the robotic system 1910. In some embodiments, the transducer array 1926 is covered with a protective layer (e.g., waterproof layer, heatproof layer, etc.). In some embodiments, the protective layer can include a hydrophilic coating which allows for bubbles, which can damage the transducer array 1926, to escape from the surface of the transducer array 1926. As seen in FIG. 20, which depicts a back view of the transducer array 1926, the transducer array 1926 is formed of trapezoidal transducer 1926a arranged in a circle. The trapezoidal transducers 1926a are each coupled to a wire 1926b that are configured to deliver electrical energy to the transducers 1926a. The histotripsy device 1920 includes a transducer array 1926 arranged in a circle, allowing the transducer array 1926 to deliver energy to a focal point F. As seen in FIG. 21, a visual aid is applied to the transducer array 1926 to depict how the transducer array 1926 is configured to direct energy to the focal point F. At the focal point F, the energy delivering from the transducer array 1926 is at a local maximum.

[0147] The focal point F can further be seen in FIG. 22 which depicts a side view of a transducer array 2126 (e.g., structurally and / or functionally similar to any of the transducer arrays described herein, such as the transducer array 226 of FIG. 2B). The transducer array 2126 includes elements disposed in a conical shape. The elements are disposed along an ellipse in the transducer array 2126 such as an ellipse El and an ellipse E2. A major axis Ml associated with the ellipse Eland a major axis M2 associated with the ellipse E2 intersect to define the focal point F. At the focal point F, the energy from the transducer array 2126 is greatest.

[0148] The histotripsy device 1920 includes a concentric imaging transducer 1924a. The concentric imaging transducer 1924a is configured to image tissue during a procedure. The histotripsy device 1920 further includes an ultrasonic imaging transducer 1924b. The ultrasonic imaging transducer 1924b is offset from the transducer array 1926 but is fixed relative to the transducer array 1926 so that the positions between them are constant. The ultrasonic imaging transducer 1924b is configured to image the tissue before beginning the procedure to allow for imaging data to be produced for registering the position of the histotripsy device 1920 to a common coordinate frame with the tissue.

[0149] The imaging device 1940 can track the motion of the robotic system 1910 and the histotripsy device 1920. The imaging device 1940 includes two cameras so that the imaging device1940 can generate three-dimensional image data. The image data from the imaging device 1940 can be utilized to register the position of the robotic system 1910 and / or the histotripsy device 1920 to the common coordinate system. In some embodiments, the imaging device 1940 can be used to track additional components such as a probe used to remove a portion of treated tissue.

[0150] Referring generally to FIGS. 23-25, the histotripsy system 1900 is shown delivering an example treatment to a tissue sample TS. The tissue sample TS is an artificial sample of tissue that is configured to be a test substitute for human tissue. The tissue sample TS can include synthetic anatomy that allows for testing the histotripsy system. FIG. 23 depicts visualization setup used with the histotripsy system of FIG. 19 engaging the tissue sample TS, according to embodiments. The visualization setup is configured to generate visualizations of the tissue sample TS as well as of the treatment applied to the tissue sample TS. The output of ane imaging array 1924b is depicted on a display 1980. The display 1980 depicts the synthetic bone in the tissue sample TS and the location of the histotripsy device 1920 in relation to the synthetic bone. The visualization allows for the surgeon to monitor the operation of the histotripsy system 1900.

[0151] In some embodiments, the transducer array 1926a is utilized the register the position of the histotripsy device 1920 in a common coordinate frame with the tissue sample TS. Similarly, the imaging device 1940 can monitor the operation of the robotic system 1910 and / or the histotripsy device 1920 to register positions and / or orientations based on the location of markers1941 (e.g., functionally and / or structurally similar to the markers 1641 of FIG. 16). After the imaging array 1924b has completed imaging of the tissue sample TS, the robotic system can rotatethe histotripsy device 1920 for treatment which can include engaging the imaging transducer 1926 with the tissue sample TS.

[0152] FIG. 24 depicts a histotripsy device 1920 of the histotripsy system 1900, with a bladder inflated and engaging the tissue sample TS. The imaging transducer 1924b and the histotripsy device 1920 are at a fixed angle so that the robotic system 1910 can rotate the histotripsy device 1920 into position based on the position of the imaging transducer 1924b during operation. The histotripsy device 1920 includes an interface 1928 (e.g., structurally and / or functionally similar to the interface 228 of FIG. 2B) for engaging with the tissue sample TS. The interface 1928 is a bladder filled with a fluid configured to allow for energy from the histotripsy device 1920 to be delivered to the tissue sample TS. The interface 1928 is flexible, as seen in FIG. 25, such that the histotripsy device 1928 can move while maintaining contact with the tissue sample TS.

[0153] FIG. 25 further depicts a close-up view of the tissue sample TS after receiving a treatment from the histotripsy device 1920. The tissue sample TS includes a target area TA. The histotripsy device 1920 applied treatment in a circular pattern 1928a around the target area TA and treatment in a linear pattern 1928b leading toward the target area TA. The linear pattern 1928b can allow for a probe or similar device to access the target area TA. As seen in FIG. 25, the histotripsy system 1900 is able to deliver a circular treatment 1928a and a linear treatment 1928b. Both the circular treatment 1928a and the linear treatment 1928b can be achieved by operating the robotic system 1910 to direct the histotripsy device 1920 in a circular pattern and a linear pattern, respectively. In some embodiments, the linear treatment 1928b can be a path formed by the histotripsy system 1900 to provide easier access for a probe (e.g., a biopsy probe) to be inserted into the tissue.

[0154] Referring generally to FIGS. 26-29, transducer array embodiments (e.g., structurally and / or functionally similar to the transducer arrays described herein) are shown that are configured for aberration correction. Aberrations can occur when the focal point of HIFU is at a different location than expected due to tissue attenuation, non-linear HIFU propagation through various types of tissue, and mistimed HIFU energy. The aberrations can include lesions in undesired locations. The embodiments described herein are configured to allow for assessing tissue attenuation, adjusting timing of transducer elements so that HIFU can be applied to a desired location, thus reducing aberrations. In some embodiments, aberrations correction can be conducted pre-operatively to determine desirable treatment parameters.

[0155] FIG. 26 schematically depicts a transducer array 2626 (e.g., structurally and / or functionally similar to any of the transducer arrays described herein such as the transducer array226 of FIG. 2B), according to embodiments. The transducer array 2626 is configured to be a component of a histotripsy device, such as the histotripsy device 120 of FIG. 1 and / or other histotripsy devices described herein. The transducer array 2626 includes, optionally a support structure 2626a and module(s) 2626b. In some embodiments, the transducer array 2626 includes a plurality of modules 2626b (e.g., lenses). The module(s) 2626b include at least one outputting element 2626c, at least one receiving element 2626d, and optionally, insulator(s) 2626e.

[0156] Each outputting element 2626c is an element that is configured to send HIFU energy toward the focal point. The receiving element 2626d is configured to receive HIFU energy reflected from the anatomy of the patient. The receiving element 2626d is configured to measure both the time and intensity of the reflection. In some embodiments, the outputting elements 2626c and the receiving elements 2626d are piezoelectric elements. In some embodiments, the piezoelectric elements are piezoelectric ceramics. In some embodiments, the outputting element 2626c is a hard (e.g., high power) piezoelectric ceramic and the receiving element 2626d is a soft (e.g., low power) piezoelectric ceramic. Including the outputting elements 2626c and the receiving elements 2626d allows for the output of the transducer array 2626 to be monitored so that the outputs of the outputting elements 2626c can be adjusted to provide desired (e.g., desired location, desired power, etc.) HIFU at the focal point. For example, based on the signals from the receiving element 2626d, the intensity and firing sequence of the outputting elements 2626c may be adjusted, thus allowing for adjustment of the transducer array 2626 during operation. This further allows for the transducer array 2626 output to be adjusted during motion of the transducer array 2626.

[0157] In some embodiments, each of the outputting elements 2626c may be separately powered to allow for independent control. In some embodiments, each of the receiving elements 2626d may be separately electrically coupled to allow for independent monitoring. The insulator(s) 2626e is configured to be disposed between the outputting element 2626c and the receiving element 2626d. The insulator 2626e may be an electrical insulator and / or a gap between the outputting elements 2626c and the receiving element 2626d. The configuration (e.g., shape, size, etc.) of the outputting element 2626c, the receiving element 2626d, and / or the insulator 2626e is configured to allow for the desired operation of the transducer array 2626. For example, the total surface area of the outputting elements 2626c may be configured to provide desired HIFU to the focal point. Example configurations are shown and described in reference to FIGS. 27A-27E.

[0158] The module(s) 2626b are portions of the transducer array 2626 that include the outputting elements 2626c, the receiving elements 2626d, and the insulator(s) 26263. The transducer array 2626 can include any amount of module(s) 2626a arranged in a symmetricallyand / or in a pattern. In some embodiments, the module(s) 2626b may be selectively coupled to the transducer array 2626 so that one or more of the modules can be replaced and / or removed for repair. In some embodiments, the outputting elements 2626c and the receiving elements 262d are arranged in a specific configuration in each module 2626b. In some embodiments, each receiving element 2626d may be include one or more associated outputting element 2626d.

[0159] The support structure 2626a is configured to provide structural support for the module(s) 2626b. In some embodiments, the support structure 2626a may be integrally formed with the module(s) 2626b. In some embodiments, the support structure 2626a may be a scaffold design with a plurality of windows. The windows can be configured to receive at least one of the outputting elements 2626c and / or the receiving elements 2626d. In some embodiments, the windows are configured to receive the module(s) 2626b In some embodiments, the outputting elements 2626c and / or the receiving elements 2626d may selectively coupled to the support structure 26267a, allowing for replacement of the elements 2626c, 2626d.

[0160] In some embodiments, the support structure 2626a may be electrically coupled to the module(s) 2626b. For example, the support structure 2626a may be configured to connect to a ground lead of the module(s) 2626b and operate as a common ground for the elements of the module(s) 2626b. Using the support structure 2626a as a ground for the module(s) 2626b may allow for a reduction in the number of wire connections, thus increasing manufacturing costs and speed.

[0161] FIGS. 27A-27E depict various transducer element configurations, according to embodiments. The transducer element configurations Generally, the configurations include outputting elements 2726c (e.g., functionally and / or structurally similar to the outputting element 2626c of FIG. 26), receiving elements 2726d (e.g., functionally and / or structurally similar to the receiving element 2626d of FIG. 26), and insulators 2726e (e.g., functionally and / or structurally similar to the insulator 2626e of FIG. 26). While the configurations of FIGS. 27A-27D include outputting elements 2726c and receiving elements 2726d in particular locations, the outputting elements 2726c and the receiving elements 2726d may be switched.

[0162] FIG. 27A depicts a circular configuration with a centrally located outputting element 2726c surrounded by the insulator 2726e. The insulator 2726e is surrounded by the receiving element 2726d. The circular configuration is configured so that the receiving element 2726d is configured to receive the reflection of the HIFU outputted by the outputting element 2726c. The sizes (e.g., radii) of the outputting element 2726c, the insulator 2726e, and / or the receiving element 21726d may be configured to allow for desired operation of a transducer array.

[0163] FIG. 27B depicts two circular outputting elements 2726c surrounded by the insulator 2726e. The insulator is surrounded by a sheet receiving element 2726d that is configured to receive reflections from either one of or both of the outputting elements 2726c. In some embodiments, the sheet receiving element 2726d can be configured to receive reflections from additional outputting elements 2726c.

[0164] FIG. 27C depicts a hexagonal configuration with a centrally located outputting element 2726c surrounded by the insulator 2726e. The insulator 2726e is surrounded by the receiving element 2726d in a hexagonal configuration. The hexagonal configuration is configured so that the receiving element 2726d is configured to receive the reflection of the HIFU outputted by the outputting element 2726c. The hexagonal configuration allows a reduction of unused space between the outputting elements 2726c when the outputting elements 2726d are arranged in a module, such as the module(s) 2626b of FIG. 26.

[0165] FIG. 27D depicts a plurality of hexagonal outputting elements 2726c arranged around hexagonal receiving elements 2726d. Each receiving element 2726d may be configured to receive the HIFU outputted by the surrounding outputting elements 2726c. The hexagonal shape of the outputting elements 2726c and the hexagonal receiving elements 2726d decreases the amount of space between the elements. In some implementations, insulators such as the insulator 2726e may be located between each of the outputting elements 2726d and the receiving elements 2726d.

[0166] FIG. 27E depicts an array of outputting elements 2726c arranged in a circular receiving element 2726d. In some embodiments, the array of outputting elements 2726c may include any number of outputting elements 2726c. In some embodiments, the outputting elements 2726c maybe uniformly located in the array. In some embodiments, the array may include outputting elements 2726c of different sizes. In some implementations, the receiving element 2726d may be a different shape (e.g., triangle, square, pentagon, hexagon, irregular shape, etc.)

[0167] FIG. 28 depicts a transducer array 2826 (e.g., functionally and / or structurally similar to the transducer array 226 of FIG. 2B, the transducer array 2626 of FIG. 26, and / or other transducer arrays described herein) with a plurality of modules 2826b (e.g., functionally and / or structurally similar to the modules 2626b of FIG. 26), according to embodiments. The transducer array 2826 includes 12 modules 2826b arranged in a circular pattern to focus HIFU away from the center of the transducer array 2826. In some embodiments, the transducer array 2826 can include a different number (e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 50, etc.). The modules 2826b, in the embodiment shown in FIG. 28, are trapezoidal. In some implementations, the modules 2826b may be shaped so that they may be arranged in any spiral pattern, geometric pattern, repeating pattern,and / or the like. In some embodiments, the shape of the modules 2827b may be determined based on a desired characteristic. For example, the desired characteristic could include reducing the number of elements.

[0168] FIG. 29 depicts a transducer 2926 (e.g., functionally and / or structurally similar to the transducer array 226 of FIG. 2B, the transducer array 2626 of FIG. 26, and / or other transducer arrays described herein) array with dimpling 2990 on a module 2926b(e.g., functionally and / or structurally similar to the modules 2626b of FIG. 26), according to embodiments. The dimpling 2990 may be arranged along at least a portion of at least one module 2926b. The dimpling 2990 can be configured to increase the surface area of the modules 2926b to aid in cooling. In some embodiments, the dimpling 2990 can be arranged along the entirety of the module 2926b or in a portion of the module 2926b. In some embodiments, each of the dimples 2990 are the same size. In some embodiments, the dimples 2990 are of various sizes. In some embodiments, the dimples 2990 are equally distributed on the module 2926b. In some embodiments, the dimples are arranged in a pattern on the module 2926b.

[0169] FIG. 30 depicts a flowchart of a method 3000 for aberration correction, according to an embodiment. The method 3000 can be used before and / or during a HIFU treatment procedure to identify aberrations associated with the tissue in the treatment area and can adjust treatment to correct for the aberrations. The method 3000 can be executed with a system, such as the system 100 of FIG. 1. The method 3000 allows for a reduction or elimination of the effects of aberrations and can allow for the HIFU to be delivered to the target area as desired with reduced damage to the surrounding tissue. The method 3000 allows for aberrations to be determined before an operation and / or during the operation to allow for desired treatment delivery.

[0170] At 3002, the method 3000 includes sending, via at least one outputting element (e.g., treatment transducer array 226 described herein, or any treatment transducers and boiling histotripsy devices described herein), a first set of signals toward an anatomical region of interest. As described above, during a boiling histotripsy procedure, ultrasonic waves can be delivered to tissue such that the waves converge on a focal point to cause boiling histotripsy. Aberrations in the tissue, however, can affect how the ultrasound waves are focused within the tissue. In particular, the ultrasonic waves must pass through multiple tissue layers (e.g., skin, fat, muscle) prior to reaching a target tissue site. When the ultrasonic waves pass through these tissue layers, aberrations in the tissue layers can alter the transmission of the ultrasonic waves, e.g., scattering the wave, which causes a loss of energy or intensity in the wave. This in turn can impact the focal point of the ultrasonic waves, and therefore the boiling histotripsy treatment. Therefore, it can beimportant to account for aberrations in tissue to adjust operating parameters of the HIFU transducers (e.g., transducers of histotripsy device 120 or other histotripsy devices described herein) to deliver the ultrasonic waves to a desired focal point. In some embodiments, the focal point can be moved along the anatomical region to interest during a boiling histotripsy procedure, so further adjustments to the operation of the transducers may be necessary intraoperatively.

[0171] In some embodiments, the first set of signals can be ultrasonic waveforms that are not intended to induce boiling histotripsy but are used to detect aberrations. The lower energy waveforms can be used for aberration identification such that the tissue is not treated during aberration identification. Alternatively or additionally, in some embodiments, the first set of signals can be ultrasonic waveforms such as HIFU waveforms that are configured to cause boiling histotripsy. At 3004, the method 3000 includes receiving, from at least one receiving element, a set of reflected signals from the anatomy of the patient. The set of reflected signals can be signals that are reflected by one or more structures within the anatomical region of interest or along the pathway taken by the ultrasonic waves to reach target tissue. In some embodiments, the set of reflected signals may change depending on the path that the ultrasonic waves take to reach a target site (e.g., a focal point).

[0172] At 3006, the method 3000 includes identifying, based on the reflected signals, one or more aberrations in the anatomical region of interest. Identifying the aberrations can include determining if the reflected signals are indicative of scatter, have certain time delays, and / or the like. At 3008, the method 3000 includes determining, based on the aberrations that are identified, one or more parameters (e.g., intensity, frequency, incident wave direction, etc.) for controlling the delivery of ultrasound waves to induce boiling histotripsy at one or more focal points. Setting the one or more parameters of the transducers based on the detected aberrations can reduce or eliminate the effects caused by the aberrations, thereby enabling more effective boiling histotripsy treatment and / or minimize damage to neighboring tissue. At 3010, the method 3000 includes delivering, via a histotripsy device based on the one or more parameters, boiling histotripsy to the anatomical region of interest.

[0173] At 3012, the method 3000 optionally includes capturing, using an imaging device, an intra-operative view of the anatomical region of interest. In some embodiments, the imaging device can be an ultrasound imaging device (e.g., imaging device 140 and / or other imaging transducers and describes described herein) and / or the like. In some embodiments, the imaging device may be operatively coupled with the histotripsy device. At 3014, the method 3000 optionally includes determining, based on the intra-operative view, that adjustments to one or moreparameters of the treatment transducers may be necessary due to one or more aberrations and / or the focal point of the treatment being offset from the intended focal point of the treatment. For example, the intra-operative view may indicate that ultrasonic energy may not be being delivered to a focal point, or an insufficient amount of energy is being delivered to the focal point. In some embodiments, boiling histotripsy may not be induced due to one or more aberrations. Systems, devices, and methods described herein can then adjust one or more parameters of the treatment transducers to deliver the energy to the focal point.

[0174] At 3016, the method 3000 optionally includes adjusting, in response to determining that boiling histotripsy is not being induced as expected, the one or more parameters. In some embodiments, adjusting can include adjusting a path, energy delivery parameters, and / or the like. At 3018, the method 3000 optionally includes delivering, via the histotripsy device based on the adjusted one or more parameters, boiling histotripsy to the target site.

[0175] 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.

[0176] 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 anorder different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.

[0177] 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.

[0178] 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.

[0179] 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, machineinstructions, 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.

[0180] 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

ClaimsWhat is claimed is:

1. A method, comprising: receiving pre-operative image data of an anatomical region of interest; capturing, using an imaging device, an intra-operative view of the anatomical region of interest; registering the pre-operative image data with the intra-operative view in a common coordinate system; determining, based on registering the pre-operative image data with the intraoperative view, a treatment path for applying boiling histotripsy to a target area in the anatomical region of interest; and delivering, via a histotripsy device and according to the treatment path, ultrasound waves to the target area to induce boiling histotripsy.

2. A method of claim 1, further comprising: receiving information associated with at least one of a status of the target area or an operation of the histotripsy device; and determining, based on the information, an adjustment to the treatment path.

3. The method of claim 2, wherein the information can include user feedback.

4. The method of claim 1, further comprising: segmenting the pre-operative image data to identify anatomical features, wherein registering the pre-operative image data and the intra-operative view is based at least in part on the segmentation of the pre-operative image data.

5. The method of claim 4, wherein the anatomical features can include at least one of a soft tissue structure, bone, or a tumor.

6. The method of claim 5, further comprising: generating a point cloud of the anatomical region of interest based on the segmentation, wherein registering the pre-operative image data and the intra-operative view is based on the point cloud.

7. The method of claim 1, further comprising: tracking the histotripsy device or another medical device; and generating a visual representation of the anatomical region of interest and the histotripsy device or other medical device based on the registering and the tracking.

8. The method of claim 7, wherein the tracking includes: capturing, using an imaging device, tracking data of the histotripsy device or other medical device.

9. The method of claim 8, further comprising: registering, based on the tracking data, a position of the histotripsy device or other medical device with the common coordinate system, wherein generating the visual representation is further based on the registering of the position of the histotripsy device or other medical device with the common coordinate system.

10. The method of claim 1, wherein the imaging device includes an ultrasound imaging device.

11. The method of claim 1, wherein the target area includes at least one of a liver, a kidney, a pancreas, a prostate, a thyroid, a lung, a colon, a muscle, a connective tissue, an eye, a heart, an artery, a vein, a nerve, blood, or a brain.

12. A system, comprising: a histotripsy device including an array of transducers configured to emit ultrasound pulses including ultrasound waves that can induce boiling histotripsy in a target area of a patient; a robotic manipulator coupled to the array of transducers and configured to move the array of transducers during a treatment procedure; a first imaging device configured to capture images of a surgical field including at least a portion of the histotripsy device and the patient; and a second imaging device configured to capture intra-operative views of an anatomical region of interest within the patient including the target area; and a processor operatively coupled to the histotripsy device and the robotic manipulator, the processor configured to:receive pre-operative image data of the anatomical region of interest; receive, from the first imaging device, image data of the surgical field including the portion of the histotripsy device and the patient, the image data of the surgical field indicative of a position of the histotripsy device; receive, from the second imaging device, an intra-operative image data of the anatomical region of interest; register the pre-operative image data with the intra-operative image data in a common coordinate system; register the position of the histotripsy device with the common coordinate system; determine, based on the registration, a treatment path for applying boiling histotripsy to the target area; and deliver, via the histotripsy device and according to the treatment path, ultrasound pulses to induce boiling histotripsy in the target area.

13. The system of claim 12, wherein the processor is further configured to control the robotic manipulator to move the histotripsy device during the delivery of the ultrasound pulses such that the delivery of the ultrasound pulses induces boiling histotripsy at multiple focal points in the target area.

14. The system of claim 12, wherein the processor is further configured to: receive information associated with at least one of a property of the target area or an operation of the histotripsy device; and determine, based on the information, an adjustment to the treatment path.

15. The system of claim 12, wherein the processor is configured to register the position of the histotripsy device with the common coordinate system by: tracking, in the image data of the surgical field, one or more markers associated with the histotripsy device; and determining, based on the tracking of the one or more markers, the position of the histotripsy device.

16. The system of claim 15, wherein the one or more markers include fiducial markers.

17. The system of claim 15, wherein the tracking is performed using a tracking algorithm, the processor being further configured to: capture, using the first imaging device, image data of the surgical field when the robotic manipulator is in one or more calibration poses; and calibrate, based on the image data of the surgical field captured when the robotic manipulator is in one or more calibration poses, the tracking algorithm.

18. The system of claim 12, wherein the first imaging device includes at least one camera.

19. The system of clam 12, wherein the second imaging device includes an ultrasound device.

20. The system of claim 12, wherein the robotic manipulator includes a plurality of segments joined via a plurality of joints, the manipulator configured to translate and rotate the histotripsy device about a plurality of axes.

21. The system of claim 12, wherein the target area includes at least one of a liver, a kidney, a pancreas, a prostate, a thyroid, a lung, a colon, a muscle, a connective tissue, an eye, a heart, an artery, a vein, a nerve, blood, or a brain.

22. A system, comprising: a histotripsy device configured to deliver boiling histotripsy to a target area of a patient, the histotripsy device including: a set of outputting elements configured to emit ultrasound waves; and a set of receiving elements configured to capture energy of the ultrasound waves that is reflected by tissue of the patient, the set of outputting elements and the set of receiving elements being arranged on a support structure in a pattern; and a processor operatively coupled to the histotripsy device, the processor being configured to: emit, using the set of outputting elements, a first set of ultrasound waves toward the target area, the first set of ultrasound waves configured to pass through layers of the tissue to reach the target area; receive, via the set of receiving elements, energy of the first set of ultrasound waves reflected by one or more structures within the layers of tissue;determine, based on the energy received by the set of receiving elements, one or more parameters for operating the set of outputting elements to induce boiling histotripsy in the target area; and emit, using the set of outputting element, a second set of ultrasound waves according to the one or more parameters such that the second set of ultrasound waves passes through the layers of tissue to induce boiling histotripsy at the target area to treat the target area.

23. The system of claim 22, wherein the histotripsy device further includes: an insulator disposed between the set of outputting elements and the set of receiving elements.

24. The system of claim 22, wherein the set of outputting elements and the set of receiving elements are piezoelectric elements.

25. The system of claim 24, wherein the piezoelectric elements are piezoelectric ceramics.

26. The system of claim 25, wherein the set of outputting elements are hard piezoelectric ceramics and the set of receiving elements are soft piezoelectric ceramics.

27. The system of claim 22, wherein the one or more treatment parameters include an intensity, a frequency, a duty cycle, or a firing sequence.

28. The system of claim 22, wherein each outputting element of the set of outputting elements is disposed such that a gap separates the outputting element from each receiving element of the set of receiving elements.

29. The system of claim 22, wherein the set of outputting elements and the set of receiving elements are arranged in a set of modules in which each module of the set of modules includes at least one outputting element, at least one receiving element, and an insulator that separates the at least one outputting element and the at least one receiving element.

30. The system of claim 22, wherein each outputting element of the set of outputting elements is concentrically arranged with respect to at least one receiving element of the set of receiving elements.

31. The system of claim 22, wherein the set of outputting elements and the set of receiving elements are arranged according to a circular pattern.

32. The system of claim 22, wherein the target area includes at least one of a liver, a kidney, a pancreas, a prostate, a thyroid, a lung, a colon, a muscle, a connective tissue, an eye, a heart, an artery, a vein, a nerve, blood, or a brain.

33. A system, comprising: a histotripsy device configured to deliver boiling histotripsy to a target area of a patient, the histotripsy device including: at least one outputting element configured to emit ultrasound waves; and at least one receiving element configured to capture energy of the ultrasound waves that is reflected by tissue of the patient; a processor operatively coupled to the histotripsy device, the processor being configured to: emit, using the at least one outputting element, ultrasound waves toward the target area, ultrasound waves configured to pass through layers of the tissue to reach the target area; receive, via the at least one receiving element, energy of the ultrasound waves reflected by the layers of tissue; determine time and intensity information of the energy reflected by the layers of tissue; identify, based on the time and intensity information, characteristics of an aberration in the anatomical region of interest; determine, based on the characteristics of the aberration, one or more parameters for operating the set of outputting elements to induce boiling histotripsy in the target area; and emit, using the at least one outputting element, ultrasound waves according to the one or more parameters to induce boiling histotripsy in the target area.

34. The system of claim 33, wherein the system further includes an imaging device, wherein the processor is further configured to: capture, using the imaging device, intra-operative views of the anatomical region of interest; monitor, using the intra-operative views, a progress of treating the target area using boiling histotripsy; adjust, based on the monitoring, the one or more parameters for operating the set of outputting elements; and emit, using the at least one outputting element and after the adjusting, ultrasound waves according to the one or more parameters.

35. The system of claim 34, wherein the processor is configured to adjust the one or more parameters by adjusting a timing or sequence of emitting the ultrasound waves.

36. The system of claim 34, wherein the processor is configured to adjust the one or more parameters by adjusting an intensity of emitting the ultrasound waves.

37. The system of claim 34, wherein the processor is configured to adjust a direction of incidence of the ultrasound waves.

38. The system of claim 33, wherein the histotripsy device further includes: at least one insulator disposed between the at least one outputting element and the at least one receiving element.

39. The system of claim 33, wherein the at least one outputting element and the at least one receiving element are piezoelectric elements.

40. The system of claim 39, wherein the piezoelectric elements are piezoelectric ceramics.

41. The system of claim 40, wherein the at least one outputting element is a hard piezoelectric ceramic and the at least one receiving element is a soft piezoelectric ceramic.

42. The system of claim 33, wherein the target area includes at least one of a liver, a kidney, a pancreas, a prostate, a thyroid, a lung, a colon, a muscle, a connective tissue, an eye, a heart, an artery, a vein, a nerve, blood, or a brain.

43. A method, comprising: determining a treatment path for treating a target tissue area using boiling histotripsy, the treatment path indicating a path of a focal point of the boiling histotripsy along the target tissue area; emitting, using an array of transducers, pulses of ultrasound waves having a duty cycle of greater than about 90% toward the target tissue area; and moving, while emitting, the array of transducers using a robotic manipulator coupled to the array of transducers, such that each treated point along the treatment path receives energy from the pulses of ultrasound waves having an effective duty cycle of less than about 10%.

44. The method of claim 43, wherein moving the array of transducers includes moving the array of transducers in at least one of translation or rotation.

45. The method of claim 43, wherein moving the array of transducers includes moving the array of transducers to apply the energy of the pulses of ultrasound waves to each treatment point along the treatment path until a lesion is formed at that treatment point.

46. The method of claim 43, wherein lesions of at least a subset of treatment points along the treatment path overlap one another.

47. The method of claim 43, wherein the target area includes at least one of a liver, a kidney, a pancreas, a prostate, a thyroid, a lung, a colon, a muscle, a connective tissue, an eye, a heart, an artery, a vein, a nerve, blood, or a brain.

48. An apparatus, comprising: a histotripsy device including: a transducer array configured to emit ultrasound waves to induce boiling histotripsy in a target area of a patient; an interface coupled to and supported by the transducer array, the interface configured to include an acoustic coupling medium that can cool the transducer array andallow for transmission of the ultrasound waves from the transducer array to the patient; and a robotic system operatively coupled to the histotripsy device, the robotic system configured to move the transducer array and the interface to treat the target area.

49. The apparatus of claim 48, wherein the interface is a bladder that is configured to hold a predetermined volume of the acoustic coupling medium.

50. The apparatus of claim 48, wherein the interface includes a coating of a fluid or gel.

51. The apparatus of claim 50, wherein the fluid is a lubricating fluid.

52. The apparatus of claim 48, wherein the interface includes: an inlet configured to receive the acoustic coupling medium; and an outlet configured to allow for escape of the acoustic coupling medium such that additional acoustic coupling medium can be cycled into the interface.

53. The apparatus of claim 48, wherein the acoustic coupling medium includes at least one of deionized water or degassed water.

54. The apparatus of claim 48, wherein the interface is configured to couple to a surface of a skin of the patient under a partial vacuum.

55. The apparatus of claim 48, wherein the transducer array is coated with a hydrophilic coating.

56. The apparatus of claim 48, wherein the target area includes at least one of a liver, a kidney, a pancreas, a prostate, a thyroid, a lung, a colon, a muscle, a connective tissue, an eye, a heart, an artery, a vein, a nerve, blood, or a brain.

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