Histotripsy system and related methods including user interface and workflow for treatment planning and treatment.

Abstract

A system and method comprising an ultrasound imaging transducer, an ultrasound therapeutic transducer, a robotic arm configured to orient the ultrasound imaging transducer and the ultrasound therapeutic transducer around a patient, a display connected to the imaging transducer, and a memory for storing instructions, wherein when an instruction is executed by a processor, the system receives an ultrasound image from the imaging transducer, presents the ultrasound image, receives input to change the shape of the contour line, presents the contour line, receives input to the size of the margin around the treatment area, presents the margin, determines the endpoints where the X, Y, and Z axes bisect the contour line in the XZ and YZ planes, drives the ultrasound therapeutic transducer to the location where the focus of the ultrasound therapeutic transducer is at the endpoint, and determines whether the resistance to movement exceeds a threshold.

Description

Technical Field

[0001] Priority Claim

[0001] This patent application claims the priority of U.S. Provisional Patent Application No. 63 / 497,277, entitled "HISTOTRIPSY SET-UP AND PLANNING SYSTEMS AND METHODS", filed on April 20, 2023, the entire disclosure of which is incorporated herein by reference.

[0002] Incorporation by Reference

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

[0003]

[0003] The present disclosure relates to a histotripsy system configured to create acoustic cavitation, methods, devices, and procedures for minimally invasive and non-invasive treatment of healthy, diseased, and / or damaged tissue. The histotripsy systems and methods described herein may include transducers, drive electronics, a positioning system including a robot, an imaging system, a patient coupling system, and integrated treatment planning and control software for providing comprehensive treatment procedures and therapies for a patient's soft and / or hard tissue. Specifically, organs or structures within the abdominal cavity (e.g., liver, kidney, spleen, pancreas, stomach, large intestine, small intestine), pelvic and reproductive tissues / organs (e.g., prostate, uterus), lungs, brain, esophagus, muscles, soft tissues such as tendons / ligaments, hard tissues such as bone, external tissues such as dermis / skin, as well as tissue on and / or partially within the skin surface, implants, and medical devices are envisioned to be used with histotripsy treatment and therapy.

Background Art

[0004]

[0004] Histotripsy or pulsed ultrasound cavitation therapy is a technique in which very short, powerful bursts of acoustic energy induce controlled cavitation (microbubble formation) within a focal volume. The active expansion and collapse of these microbubbles mechanically homogenizes the cellular and tissue structures within the focal volume. This is a very different end result from the coagulation-necrotic properties of thermal ablation. In order to act within the non-thermal histotripsy range, the acoustic energy must be delivered in the form of high-amplitude, very short acoustic pulses, typically with a low duty cycle.

[0005]

[0005] Compared to conventional focused ultrasound techniques, histotripsy has significant advantages. Specifically, 1) the destructive process at the focal point is mechanical rather than thermal; 2) cavitation appears bright on the ultrasound image, thereby confirming proper targeting and localization of the treatment; 3) the treated tissue appears generally, though not necessarily, darker (less echogenic) on the ultrasound image, allowing the operator to see what has been treated; and 4) histotripsy causes destruction in a controlled and precise manner. It is important to emphasize that, unlike thermal ablation techniques such as microwave, radiofrequency, high-intensity focused ultrasound (HIFU), cryo, or radiation, histotripsy relies on the mechanical action of cavitation for tissue destruction and does not rely on thermal, cold, or ionizing energy. Despite these obvious advantages, improvements to the method and system are always desired. [Overview of the Initiative] [Means for solving the problem]

[0006]

[0006] One aspect of the present disclosure relates to a histotripsy system comprising an ultrasound imaging probe and an ultrasound therapeutic transducer coupled to the ultrasound imaging probe. The histotripsy system also includes a robotic arm configured to align the orientation of an ultrasound imaging probe and an ultrasound therapeutic transducer around a patient, a display operably connected to the imaging probe, and a memory for storing instructions. When instructions are executed by a processor operably connected to the memory, the system receives a live ultrasound image from the ultrasound imaging probe, presents the live ultrasound image on the display's user interface, receives input via the user interface to modify the shape of the treatment contour around the treatment area in the live ultrasound image, presents contour lines representing the treatment contour on the ultrasound image in the user interface, receives input via the user interface to the size of the margin around the treatment area, presents margin lines representing the margin on the ultrasound image in the user interface, determines the investigation points where the X, Y, and Z axes bisect the margin lines in the XZ and YZ planes, receives input to drive the ultrasound therapeutic transducer to a location where its focus is at one of the investigation points, and determines whether the resistance to movement of the ultrasound therapeutic transducer exceeds a threshold. Other embodiments of this aspect include corresponding computer systems, apparatuses, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.

[0007]

[0007] Implementations of this aspect of the Disclosure may include one or more of the following features: A histotripsy system in which inputs for modifying the shape of the treatment contour around a treatment area are received via a user interface in the XZ and YZ planes of a live ultrasound image. Inputs for driving an ultrasound therapeutic transducer are received via a user interface on a display. Inputs for driving the ultrasound therapeutic transducer are received for each survey point. If it is determined that the resistance to movement of the ultrasound therapeutic transducer does not exceed a threshold while driving to reach all survey points, the planned treatment is accepted and stored in memory. If it is determined that the resistance to movement of the ultrasound therapeutic transducer exceeds a threshold while driving to reach any of the survey points, the instruction stored in memory and executed by the processor causes the user interface to present a mitigation instruction. The histotripsy system further includes presenting representations of contour lines and survey points in separate fields of the user interface. Inputs for driving the therapeutic transducer are received via representations of contour lines and survey points in separate fields of the user interface. An indicator is displayed when the therapeutic transducer moves to a location where the focus coincides with the area of ​​investigation. When the command is executed by the processor, it receives input to the location of the intersection of the muscle and fat layers in the live ultrasound image. When the command is executed by the processor, it triggers the activation of a knob, which, when operated, adjusts a parameter displayed on the indicator on the user interface. The knob adjusts the contour along the x, y, and z axes. The knob adjusts the size of the margin around the contour. The knob adjusts the focus of the therapeutic transducer. Implementations of the described technology may include hardware, methods, or processes, or computer software on a computer-accessible medium, including software, firmware, hardware, or a combination thereof installed on the system that produces an action when in operation or causes the system to perform an action.One or more computer programs can be configured to perform a specific operation or action by including instructions that, when executed by a data processing device, cause the device to perform an action.

[0008]

[0008] Further aspects of the present disclosure relate to a method for planning a histotripsy treatment. The method includes displaying a live ultrasound image on a user interface. The method also includes moving an ultrasound assembly to a mark on the patient from which a treatment area within the patient can be observed in the live ultrasound image; presenting a contour line around the treatment area in the live ultrasound image on the user interface; adjusting the contour line in the live ultrasound image; identifying a survey point where the X, Y, and Y axes intersect the contour line in the XZ and YZ planes; displaying a margin around the contour line; displaying the focus of a therapeutic transducer, from which the therapeutic transducer is a component of the ultrasound assembly; driving the ultrasound assembly so that the focus of the therapeutic transducer coincides with at least one of the survey points; and detecting resistance to the movement of the ultrasound assembly as the ultrasound assembly moves to reach at least one of the survey points. Other embodiments of this aspect include corresponding computer systems, apparatuses, and computer programs recorded on one or more computer storage devices, each configured to perform the methods and system operations described herein.

[0009]

[0009] Implementations of this aspect of the Disclosure may include one or more of the following features: The method further includes comparing resistance to movement with a threshold. The method further includes modifying the shape of the contour around a treatment area in the XZ and YZ planes of a live ultrasound image. An ultrasound assembly is driven by robotic control to each survey point. If it is determined that the resistance to movement of the treatment transducer does not exceed a threshold while being driven to reach each of the survey points, the planned treatment is accepted and stored in memory. The method further includes receiving indications of the location of the intersection of the muscle layer and the fat layer in the live ultrasound image. Implementations of the described techniques may include hardware, methods, or processes, or computer software on a computer-accessible medium, including software, firmware, hardware, or a combination thereof installed on a system that produces an action when in operation or causes the system to perform an action. One or more computer programs may be configured to perform a particular operation or action by including instructions that, when executed by a data processing device, cause the device to perform an action.

[0010]

[0010] In one embodiment, the system includes an ultrasound imaging system, an ultrasound therapeutic transducer coupled to the ultrasound imaging system, a robotic arm configured to position the ultrasound imaging system and the ultrasound therapeutic transducer relative to the patient and the treatment site, a display operably connected to the ultrasound imaging system, and a memory for storing instructions. When an instruction is executed by a processor operably connected to the memory, the system receives a real-time ultrasound image from the ultrasound imaging system, presents the live ultrasound image on the user interface of the display, identifies the target, and, via the user interface, determines the treatment volume in the live ultrasound image. A histotripsy system is provided that receives input to change the shape of the surrounding target contour, presents a target contour line representing the target contour on the ultrasound image in the user interface, receives input to change the size of the margin around the target region via the user interface, presents a margin contour line representing the margin contour on the ultrasound image in the user interface, determines the investigation points where the X, Y, and Z axes bisect the margin line in the XZ and YZ planes, receives input to drive the ultrasound therapeutic transducer to a location where the focal point of the ultrasound therapeutic transducer is at one of the investigation points, and determines whether the resistance to the movement of the ultrasound therapeutic transducer exceeds a threshold.

[0011]

[0011] Depending on the embodiment, input for changing the shape of the treatment contour around the treatment volume is received via the user interface in the XZ and YZ planes of the live ultrasound image.

[0012]

[0012] Depending on the configuration, the input for driving the ultrasonic therapy transducer is received via a user interface in the display.

[0013]

[0013] Depending on the configuration, the input for driving the ultrasonic therapy transducer is received for each investigation point.

[0014]

[0014] Depending on the configuration, if it is determined that the resistance to the movement of the ultrasonic treatment transducer does not exceed a threshold while it is being driven to reach all of the survey points, the planned treatment is accepted and stored in memory.

[0015]

[0015] In one embodiment, if it is determined that the resistance to the movement of the ultrasonic therapy transducer exceeds a threshold while it is being driven to reach any of the survey points, an instruction stored in memory and executed by the processor causes the user interface to present a mitigation instruction.

[0016]

[0016] Depending on the embodiment, the system may include presenting the contour lines and survey points in separate fields of the user interface.

[0017]

[0017] In another embodiment, inputs that drive a therapeutic transducer are received through representations of contours and survey points in separate fields of the user interface.

[0018]

[0018] The histotripsy system of claim 7 further includes an indicator shown on a survey point in a separate field representation of the user interface, the indicator indicating when a therapeutic transducer moves to a location where the focus coincides with the survey point.

[0019]

[0019] In some embodiments, when the instruction is executed by the processor, it receives input of the location of the intersection of the muscle layer and the fat layer in a live ultrasound image.

[0020]

[0020] In another embodiment, when an instruction is executed by the processor, it triggers the activation of a knob, which, when operated, adjusts a parameter displayed on an indicator on the user interface.

[0021]

[0021] Depending on the embodiment, the knob adjusts the contour along the X, Y, and Z axes.

[0022]

[0022] In another aspect, the knob adjusts the size of the margin around the contour.

[0023]

[0023] In some aspects, the knob adjusts the focal location of the treatment transducer.

[0024]

[0024] Displaying a live ultrasound image on a user interface, moving the ultrasound assembly from the live ultrasound image to a mark on the patient where a treatment area within the patient can be observed therefrom, presenting a contour line around the treatment volume in the live ultrasound image on the user interface, adjusting the contour line in the live ultrasound image, identifying interrogation points where the X, Y, and Z axes intersect the contour line in the XZ and YZ planes, displaying a margin around the contour line, displaying the focus of the treatment transducer, where the treatment transducer is a component of the ultrasound assembly, driving the ultrasound assembly so that the focus of the treatment transducer coincides with at least one of the interrogation points, and detecting a resistance to the movement of the ultrasound assembly as it moves to reach at least one interrogation point, a method for planning a histotripsy procedure is provided.

[0025]

[0025] In some aspects, the method includes comparing the resistance to movement to a threshold.

[0026]

[0026] In another aspect, the method includes changing the shape of the contour line around the treatment area in the XZ and YZ planes of the live ultrasound image.

[0027]

[0027] In some aspects, the ultrasound assembly is robotically controlled to each interrogation point.

[0028]

[0028] In one aspect, if it is determined that the resistance to the movement of the treatment transducer does not exceed the threshold during driving to reach each of the interrogation points, the planned treatment is accepted and stored in memory.

[0029]

[0029] In some embodiments, the method includes receiving an indication of the location of the intersection of the muscle layer and the fat layer in the live ultrasound image.

[0030]

[0030] Navigating the treatment transducer to align the focus at the center of the planned treatment volume, activating the histotripsy pulse, raising the voltage associated with the histotripsy pulse until bubble cloud / acoustic cavitation occurs, marking the center of the bubble cloud, and navigating the treatment transducer to a plurality of interrogation points around the planned treatment volume, where at each interrogation point, the voltage associated with the histotripsy pulse is activated and raised until a bubble cloud is generated / formed, and starting an automatic treatment plan, where the treatment transducer is robotically controlled to drive to a plurality of focus locations within the planned treatment volume and the histotripsy pulse is applied at each focus location. A histotripsy treatment method is provided.

[0031]

[0031] In some embodiments, the method includes interpolating the ultrasonic energy required for each focus location based on the voltage applied at each of the interrogation points and at the center of the planned treatment volume.

[0032]

[0032] In one embodiment, the treatment transducer is driven to each focus location in a sequential pattern until all focus locations within the planned treatment volume receive individualized histotripsy pulses.

[0033]

[0033] In another embodiment, it is confirmed that the bubble cloud generated at each interrogation point coincides with the focus of the treatment transducer.

[0034]

[0034] In some embodiments, following completion of the automatic treatment plan, the voltage knob associated with the treatment energy source is deactivated.

[0035]

[0035] In another embodiment, the method includes confirming that all focal locations have received a histotripsy pulse.

[0036]

[0036] Depending on the embodiment, this may include visualizing the planned treatment volume after the completion of the treatment plan in order to confirm complete treatment.

[0037]

[0037] In one embodiment, visualization is performed using an ultrasound imaging probe.

[0038]

[0038] In another embodiment, the first of a plurality of survey points to which the therapeutic transducer is navigated is the -Z survey point.

[0039]

[0039] In one embodiment, the method includes calculating the offset between the center of the bubble cloud and the focus of the therapeutic transducer.

[0040]

[0040] In some embodiments, the method includes using an offset to calibrate the placement of the therapeutic transducer so that it reaches each investigation point.

[0041]

[0041] Depending on the embodiment, the method includes displaying an automated treatment plan on a user interface, the automated treatment plan defining one or more of the volume to be treated, the depth of the plan, and the margins.

[0042]

[0042] In one embodiment, the user interface displays treatment indications at each focal point of the planned treatment volume following the application of histotripsy pulses to the focal points.

[0043]

[0043] Depending on the embodiment, the user interface may display an indication of which focal location of the planned treatment volume is currently receiving a histotripsy pulse.

[0044]

[0044] In one embodiment, the method includes a user interface for displaying an ultrasound image acquired by an ultrasound imaging transducer, wherein the ultrasound image shows at least a portion of the planned treatment volume.

[0045]

[0045] Depending on the configuration, when a histotripsy pulse is applied, the bubble cloud can be seen in an ultrasonic image.

[0046]

[0046] In one embodiment, the method further includes showing one or more of the focus, planned treatment volume, margin, or sound field of the therapeutic transducer on the ultrasound image.

[0047]

[0047] Depending on the configuration, ultrasound imaging is continued throughout the entire automated treatment plan so that the histotripsy pulses for each focal point are visualized.

[0048]

[0048] In one embodiment, the ultrasound image is a fused ultrasound image shown in combination with a preoperative image set.

[0049]

[0049] In some embodiments, the method further includes detecting resistance to movement of a therapeutic transducer and displaying a resistance indicator on a user interface.

[0050]

[0050] A method for fusing images is provided, which includes navigating a composite imaging and therapeutic transducer assembly to a location on a patient that enables visualization of a region of interest; performing an ultrasound sweep using the imaging transducers of the composite imaging and therapeutic transducer assembly to capture a number of ultrasound images; marking registration points in ultrasound images from the ultrasound sweep; marking registration points in images from a preoperative image set; fusing the preoperative image set with the ultrasound images from the ultrasound sweep to form a fused image; reviewing the fused image; accepting the fusion; and displaying a live ultrasound image fused with the preoperative image set on a user interface.

[0051]

[0051] In one embodiment, the method includes verifying that the combined imaging and therapeutic transducer assembly is located substantially in the center of the region of interest in multiple planes.

[0052]

[0052] Depending on the embodiment, the method includes marking a plurality of registration points in the image from the ultrasound sweep and a plurality of registration points in the preoperative image set.

[0053]

[0053] In one embodiment, the method further includes initiating the patient to hold their breath before performing an ultrasonic sweep.

[0054]

[0054] Depending on the embodiment, the method may include adjusting the orientation and position of a combined imaging and therapeutic transducer assembly to optimize visualization of the region of interest by the imaging transducer.

[0055]

[0055] In another embodiment, the method includes rotating the imaging transducer of the composite imaging and therapeutic transducer assembly by 90 degrees to confirm visualization of the region of interest.

[0056]

[0056] Depending on the embodiment, the method may include displaying an ultrasonic image captured during an ultrasonic sweep.

[0057]

[0057] In one embodiment, the method includes editing the ultrasound images captured during the ultrasound sweep.

[0058]

[0058] Depending on the embodiment, the only image remaining after image editing is the image showing the region of interest.

[0059]

[0059] In another embodiment, the registration points placed in the ultrasound image correspond to the registration points in the preoperative image set and are placed on anatomical landmarks that appear in both the ultrasound image and the preoperative image set.

[0060]

[0060] Depending on the embodiment, the method may include determining whether sufficient anatomical landmarks were identified in the ultrasound images and the preoperative image set.

[0061]

[0061] In another embodiment, the system includes locating at least one registration point in a plurality of ultrasound images and at least one registration point in a plurality of images from a set of preoperative images.

[0062]

[0062] Depending on the embodiment, the method may include adjusting the position of the registration point in the ultrasound image or the position of the registration point in the preoperative image set.

[0063]

[0063] Depending on the embodiment, the method includes adjusting the registration of the images from the ultrasound sweep with respect to the preoperative image set by dragging or rotating at least one image from the preoperative image set relative to the images from the ultrasound sweep.

[0064]

[0064] In other embodiments, the method includes verifying the alignment of the patient's biological structures in live ultrasound images and preoperative image sets.

[0065]

[0065] In one embodiment, the method includes rotating the imaging transducer of the combined imaging and therapeutic transducer assembly by 90 degrees in order to verify the alignment.

[0066]

[0066] In another embodiment, the method includes adjusting a displayed live ultrasound image fused with a preoperative image set.

[0067]

[0067] A system configured for use in accordance with the method claims described above is also provided.

[0068]

[0068] A method for planning histotripsy treatment is provided, comprising: firstly, visualizing a target treatment volume using an ultrasound imaging system; displaying a target contour around the treatment volume in an ultrasound image generated by the ultrasound imaging system; adjusting the target contour around the treatment volume in the first plane; confirming that there are substantially no obstructions in the acoustic path of a therapeutic transducer in the first plane; secondly, visualizing a target treatment volume using an ultrasound imaging system; displaying a target contour around the treatment volume in a second ultrasound image generated by the ultrasound imaging system; adjusting the target contour around the treatment volume in the second plane; and confirming that there are substantially no obstructions in the acoustic path of a therapeutic transducer in the second plane.

[0069]

[0069] Depending on the embodiment, the target contour of the first surface and the target contour of the second surface define the volume for treatment.

[0070]

[0070] In another embodiment, the method includes displaying a margin around the treatment volume.

[0071]

[0071] Depending on the embodiment, the method may include defining multiple survey points for the treatment volume.

[0072]

[0072] Depending on the embodiment, the survey point is located at the point where the center of the treatment volume and the three orthogonal axes extending outward from the center of the treatment volume intersect the margin.

[0073]

[0073] In one embodiment, the axes are X, Y, and Z.

[0074]

[0074] In another embodiment, the first surface is the YZ plane.

[0075]

[0075] Depending on the embodiment, the second surface is the XZ plane.

[0076]

[0076] Adjusting the target contour of the first surface adjusts the diameter of the treatment volume along the Y axis and the diameter of the treatment volume along the Z axis.

[0077]

[0077] The method includes confirming that the target contour of the first face is located at the center of the YZ plane and the target contour of the second face is located at the center of the XZ plane.

[0078]

[0078] In one embodiment, the method includes receiving a selection of one of the survey points.

[0079]

[0079] Depending on the embodiment, the method may include robotically controlling the therapeutic transducer to a selected investigation point.

[0080]

[0080] In some embodiments, the method further includes detecting resistance to movement of the therapeutic transducer while it is moving to a selected investigation point.

[0081]

[0081] Depending on the configuration, if the detected resistance value exceeds a threshold, an indicator or threshold is shown.

[0082]

[0082] In another embodiment, the method includes detecting whether the value of the resistance exceeds a second threshold and stopping the robotic movement of the therapeutic transducer.

[0083]

[0083] In one embodiment, the method includes adjusting one of the target contour or margin of the treatment volume or the focus of the treatment transducer and driving to the investigation point.

[0084]

[0084] Depending on the embodiment, the method may include receiving confirmation that all inspection points have been driven to.

[0085]

[0085] In another embodiment, the method includes receiving an indication of the location of the intersection of the muscle layer and the fat layer via a user interface.

[0086]

[0086] In some embodiments, the method includes receiving verification that the therapeutic volume is within the target contour of the first plane and the target contour of the second plane throughout the entire respiratory cycle.

[0087]

[0087] Depending on the embodiment, the level of the bonding medium in the bonding vessel in which the therapeutic transducer is located is sufficient to ensure ultrasonic coupling at all investigation points. [Brief explanation of the drawing]

[0088] [Figure 1A]

[0088] This figure shows the histripsy system according to the present disclosure. [Figure 1B] This figure shows the histripsy system according to this disclosure. [Figure 2]

[0089] This figure shows a therapeutic and imaging assembly of a histotripsy system according to the present disclosure. [Figure 3A]

[0090] This flowchart outlines the treatment method described in this disclosure. [Figure 3B]

[0091] This flowchart outlines the method for initializing the histotripsy system shown in Figure 1, as disclosed in this information. [Figure 4]

[0092] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 5A] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 5B] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 6] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 7A] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 7B] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 8] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 9] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 10A] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 10B] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 10C] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 11] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 12] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 13] This figure shows a series of user interface images following the steps of the flowchart in Figure 3B, as disclosed herein. [Figure 14]

[0093] This flowchart outlines the setup method for the histotripsy system and binding chamber shown in Figure 1, according to this disclosure. [Figure 15]

[0094] This figure shows a user interface illustrating the details of the initial steps of the method shown in Figure 14 according to this disclosure. [Figure 16]

[0095] This figure shows the coupling chamber and therapeutic and imaging assembly according to the present disclosure. [Figure 17]

[0096] This figure shows a series of user interface images following the steps of the flowchart in Figure 14, as disclosed herein. [Figure 18] This figure shows a series of user interface images following the steps of the flowchart in Figure 14, as disclosed herein. [Figure 19] This figure shows a series of user interface images following the steps of the flowchart in Figure 14, as disclosed herein. [Figure 20] This figure shows a series of user interface images following the steps of the flowchart in Figure 14, as disclosed herein. [Figure 21] This figure shows a series of user interface images following the steps of the flowchart in Figure 14, as disclosed herein. [Figure 22] This figure shows a series of user interface images following the steps of the flowchart in Figure 14, as disclosed herein. [Figure 23]

[0097] This flowchart outlines a method for generating a fused image dataset for display in the user interface of the histotripsy system shown in Figure 1, as disclosed herein. [Figure 24]

[0098] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 25] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 26] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 27] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 28] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 29] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 30] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 31] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 32] This figure shows a series of user interface images following the steps of the flowchart in Figure 23, as disclosed herein. [Figure 33A]

[0099] This flowchart outlines the method for planning histotripsy treatment as described in this disclosure. [Figure 33B] This flowchart outlines the method for planning histotripsy treatment as described in this disclosure. [Figure 34]

[0100] This figure shows a series of user interface images following the steps of the flowcharts in Figures 33A and 33B as disclosed herein. [Figure 35] This figure shows a series of user interface images following the steps of the flowcharts in Figures 33A and 33B as disclosed herein. [Figure 36] This figure shows a series of user interface images following the steps of the flowcharts in Figures 33A and 33B as disclosed herein. [Figure 37]This figure shows a series of user interface images following the steps of the flowcharts in Figures 33A and 33B as disclosed herein. [Figure 38] This figure shows a series of user interface images following the steps of the flowcharts in Figures 33A and 33B as disclosed herein. [Figure 39] This figure shows a series of user interface images following the steps of the flowcharts in Figures 33A and 33B as disclosed herein. [Figure 40] This figure shows a series of user interface images following the steps of the flowcharts in Figures 33A and 33B as disclosed herein. [Figure 41]

[0101] This flowchart outlines the method for performing treatment for histotripsy as disclosed herein. [Figure 42A]

[0102] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 42B]

[0102] This figure shows a series of user interface images following the steps of the flowchart in Figure 41 according to the present disclosure. [Figure 42C]

[0102] This figure shows a series of user interface images following the steps of the flowchart in Figure 41 according to the present disclosure. [Figure 43A] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 43B] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 44] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 45] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 46]This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 47] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 48] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 49A] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 49B] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 49C] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 49D] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 49E] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 49F] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 49G] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 50] This figure shows a series of user interface images following the steps of the flowchart in Figure 41, as disclosed herein. [Figure 51]

[0103] This is a schematic diagram illustrating the histotripsy system as disclosed herein. [Figure 52]

[0104] This figure shows a UI and workflow specifically designed for detecting persistent cavitation. [Figure 53]

[0105] This diagram shows the UI and workflow for initiating aberration correction calibration. [Figure 54]

[0106] This diagram shows the workflow and UI for guiding users through the acquisition of CBCT images of target tissues. [Figure 55A] This diagram shows the workflow and UI for guiding users through the acquisition of CBCT images of target tissues. [Figure 55B] This diagram shows the workflow and UI for guiding users through the acquisition of CBCT images of target tissues. [Figure 56]

[0107] This diagram shows a UI that customizes treatment and setup workflows based on the type of treatment head, imaging type, target organ, and / or room setup. [Modes for carrying out the invention]

[0089]

[0108] This disclosure relates to systems and methods for histotripsy, as well as histotripsy systems. According to this disclosure, one embodiment relates to a system and method for verifying the placement of a treatment head assembly, including a focused ultrasound therapeutic transducer (e.g., a histotripsy therapeutic transducer), located outside the patient, aligned and positioned in a region of interest, including target tissue and a planned treatment volume. In some embodiments, the system is configured to include mechanisms for assisting localization, targeting, and verification that the target tissue is visible within the planned treatment volume under ultrasound imaging before the commencement of the treatment delivery phase of the procedure. In other embodiments, tracking ultrasound imaging can be used to align a secondary imaging modality (e.g., CT, MRI, CBCT, contrast-enhanced ultrasound, etc.) with live ultrasound imaging to further enhance visualization of the region of interest and target tissue. These methods allow the systems described herein to be positioned and configured to minimize or avoid energy interference and absorption by tissues (e.g., bone or intestinal gas), thereby reducing the energy required to initiate or maintain histotripsy treatment, and minimizing damage to pre-lesion and interstitial tissues. Furthermore, to maintain an acceptable level of safety throughout the entire duration of the procedure, forces applied to the patient or treatment assembly are measured, monitored, and (if necessary) addressed. These system mechanisms are designed to ensure the safety of the patient, the system, and system components. In addition, these system mechanisms ensure that the biological structures, organs, and other soft tissues of interest are not moved or altered in an unacceptable manner during the procedure.Furthermore, based on unique and heterogeneous patient-specific treatment scenarios that consider various locations, sizes, and tissue pathways to target tissue locations, as well as patient-specific variables (such as body mass index and biostructure), an in-situ treatment plan is created for the user-defined 3D planned treatment volume. The system then proceeds according to the plan, delivering one or more histotripsy pulse sequences in one or more treatment zones and defined focal locations, ensuring that complete treatment is delivered to the treatment volume, including the user-defined margins, using specific treatment patterns and pathways when delivered.

[0090] Histotripsy

[0109] Histotripsy involves short, high-amplitude focused ultrasound pulses to generate a dense, active “bubble cloud” capable of targeted tissue fragmentation and destruction. Histotripsy can produce controlled tissue erosion when directed at tissue interfaces, including tissue / fluid interfaces, and clear tissue fragmentation and destruction at subcellular levels when bulk tissue is targeted. Unlike other forms of ablation, including thermal and radiation-based modalities, histotripsy does not rely on heat or ionization (high) energy to treat tissue. Instead, histotripsy utilizes acoustic cavitation generated at the focus to mechanically act on tissue structure and, in some cases, to liquefy, suspend, solubilize, and / or destroy tissue into subcellular components.

[0091]

[0110] Histotripsy can be applied in various forms, including: 1) Intrinsic-Threshold Histotripsy, i.e., delivering a pulse with at least one negative / tensile phase sufficient to induce inertial cavitation in a population of medium-specific bubble nuclei. 2) Shock scattering histotripsy, i.e., delivering a pulse with a duration of approximately 3–20 periods. The amplitude of the tensile phase of the pulse is sufficient to induce inertial cavitation in the bubble nuclei in the medium within the focal zone for the duration of the pulse. These nuclei scatter the incident shock wave, which inverts the incident wave to exceed the threshold for intrinsic nucleation and constructively interferes with such an incident wave. 3) Boiling histotripsy, i.e., employing a pulse with a duration of approximately 1–20 milliseconds. The absorption of the shock pulse rapidly heats the medium, thereby lowering the threshold for intrinsic nuclei. When this intrinsic threshold coincides with the peak negative pressure of the incident wave, boiling bubbles are formed at the focal point.

[0092]

[0111] The high pressure generated at the focal point causes a cloud of acoustic cavitation bubbles above a certain threshold, thereby generating localized stress and strain and mechanical yielding within the tissue without significant heat accumulation. At pressure levels where cavitation does not occur, minimal effects are observed on the tissue at the focal point. This cavitation effect is observed only at pressure levels significantly higher than those defining the inertial cavitation threshold in water over similar pulse durations, with peak negative pressures on the order of 10–30 MPa.

[0093]

[0112] Histotripsy can be performed in multiple ways and under different parameters. Histotripsy can be performed completely non-invasively by acoustically coupling a focused ultrasound transducer over the patient's skin and transcutaneously delivering acoustic pulses through the overlying (and intervening) medium and tissue to the focal zone (treatment zone and site). Histotripsy can further be targeted, planned, directed, and observed under direct visualization via ultrasound imaging, assuming that the resulting bubble cloud may appear as a highly dynamic echogenic region on, for example, a B-mode ultrasound image, thereby enabling continuous visualization throughout its use (and associated procedures). Similarly, fragmented tissue being treated will exhibit dynamic changes (typically decreases) in echointensity, which can be used for treatment evaluation, planning, observation, and monitoring.

[0094]

[0113] Generally, in the treatment of histotripsy, an ultrasonic pulse with one or more acoustic periods is applied, and bubble cloud formation depends on pressure release scattering (sometimes exceeding 100 MPa, P+) from the initial sparsely distributed bubbles (or a single bubble) that are released in front of the positive shock wave. This is called the "shock scattering mechanism."

[0095]

[0114] This mechanism relies on one (or a few sparsely distributed) bubbles starting from the initial negative half-period of the pulse at the transducer's focus. Next, a cloud of microbubbles is formed due to backscattering resulting from the pressure release of the high positive peak shock wave front from these sparse initial bubbles. These backscattered high-amplitude rarefied waves exceed the intrinsic threshold, thereby generating a localized, high-density bubble cloud. Then, each subsequent acoustic period induces further cavitation due to backscattering from the bubble cloud surface growing toward the transducer. As a result, an elongated, high-density bubble cloud growing along the acoustic axis in the opposite direction to the ultrasonic propagation is observed by the shock scattering mechanism. This shock scattering process makes bubble cloud formation dependent not only on the peak negative pressure but also on the number of acoustic periods and the amplitude of the positive shock. In the absence of at least one strong shock wave front formed by nonlinear propagation, a high-density bubble cloud does not form when the negative peak half-period falls below the intrinsic threshold.

[0096]

[0115] When ultrasonic pulses of less than two cycles are applied, shock scattering can be minimized, and the formation of a dense bubble cloud depends on the negative half-cycle of the applied ultrasonic pulse that exceeds the "intrinsic threshold" of the medium. This is called the "intrinsic threshold mechanism."

[0097]

[0116] This threshold can range from 26 to 30 MPa for soft tissues with high water content, such as human tissue. Depending on the embodiment, this intrinsic threshold mechanism can be used to clearly define and make more predictable the spatial extent of fracture. A peak negative pressure (P-) not significantly higher than this threshold can produce subwavelength reproducible fracture as small as half the transducer's -6 dB beamwidth.

[0098]

[0117] High-frequency histotripsy pulses result in smaller minimum reproducible fracture sizes, which is advantageous in applications requiring precise fracture induction. However, high-frequency pulses are susceptible to attenuation and aberration, leading to problematic treatments at deeper penetration depths (e.g., deep body ablation) or through highly aberrated media (e.g., transcranial procedures or procedures where the pulse travels through bone). Histotripsy can also be applied as low-frequency "pump" pulses (typically <2 periods and with frequencies between 100 kHz and 1 MHz) and in conjunction with high-frequency "probe" pulses (typically <2 periods and with frequencies greater than 2 MHz or between 2 MHz and 10 MHz), in which case the peak negative pressures of the low-frequency and high-frequency pulses constructively interfere to exceed an intrinsic threshold in the target tissue or medium. Low-frequency pulses, which are more tolerant of attenuation and aberrations, can increase the peak negative pressure (P-) level for the region of interest (ROI), while high-frequency pulses, which offer greater precision, can precisely target a specific location within the ROI and raise the peak negative pressure (P-) above the intrinsic threshold. This technique is sometimes called "dual frequency," "dual beam histotripsy," or "parametric histotripsy."

[0099]

[0118] Additional systems, methods, and parameters for delivering optimized histotripsy using impact scattering, intrinsic thresholds, and various parameters, enabling frequency synthesis and bubble manipulation, including additional means for controlling the histotripsy effect with respect to steering and positioning the focus at the treatment site or within intervening tissue and simultaneously managing tissue effects (e.g., pre-thermal incidental damage), are included herein as part of the systems and methods disclosed herein. Also disclosed, including future anticipated embodiments, are various systems and methods, which may include, but are not limited to, multiple parameters such as frequency, operating frequency, center frequency, pulse repetition frequency, pulse, burst, pulse count, period, pulse length, pulse amplitude, pulse duration, delay, burst repetition frequency, sets of the former, loops of multiple sets, loops of multiple and / or different sets, sets of loops, and various combinations or substitutions thereof, are included herein as part of the disclosure. This further includes the ability to vary these parameters spatially and temporally throughout the treatment and treatment plan.

[0100] Integrated imaging

[0119] The disclosed system may include a variety of imaging modalities that enable the user to visualize, monitor, and collect / use feedback on the patient's biostructure, relevant regions of interest and treatment / procedure sites, and surrounding and intervening tissues, in order to evaluate, plan, perform, and adjust treatment parameters as necessary. Imaging modalities may include a variety of ultrasound, X-ray, CT, MRI, PET, fluoroscopy, optics, contrast or agent-enhanced versions, and / or various combinations thereof. It is further disclosed that a variety of image processing and characterization techniques may also be used to enable enhanced visualization and user decision-making. These may be selected or directed by the user manually or automated by the system. The system may be configured to enable parallel, toggle, overlay, 3D reconstruction, segmentation, registration, multimodal image fusion, image flow, and / or any other method, enabling the user to identify, define, and be notified of various modes of using imaging during a procedure when displayed on a variety of system user interfaces and displays. Examples may include, but are not limited to, the locating, indicating, and characterizing potential treatment sites within, on, and / or surrounding areas of interest, organ systems, organs, or tissues; identifying important structures such as tubes, blood vessels, nerves, ureters, fissures, sacs, tumors, tissue damage / injury / disease, other organs, and connective tissue, and / or one or more interrelated structures (e.g., tumor drainage lymph nodes or vascular structures, or tumors adjacent to or beneath organ sacs).

[0101]

[0120] The system may be configured to include onboard integrated imaging hardware, software, sensors, probes, and wetware, and / or to communicate with and interface with external imaging and image processing systems. The aforementioned components may be incorporated into a component in which probes, imaging arrays, etc., are electrically, mechanically, or electromechanically integrated into the therapeutic transducer. This can partially provide the ability to have geometrically aligned imaging and treatment with the treatment directly in the field of view and, in some cases, coincided with the imaging. In some embodiments, this integration may include a fixed orientation of the imaging function (e.g., imaging probe) in relation to the therapeutic transducer. In other embodiments, the imaging solution may be able to move or adjust its position, including modification of angle, extension (e.g., distance from the therapeutic transducer or patient), rotation (e.g., imaging plane in the example of an ultrasound probe), and / or other parameters, including moving / adjusting while actively performing imaging. The imaging component or probe may be encoded so that its orientation and position relative to the therapeutic transducer and / or other aspects of the system, such as a robot-controllable positioning component, can be determined. Furthermore, the imaging components or probes may be aligned with the robotic system in relation to one or more imaging components or probes to accurately locate / display the focus of the treatment system.

[0102]

[0121] In one embodiment, the system may include an onboard ultrasound system further configured to allow the user to visualize, monitor, and receive feedback on the treatment site via a system display and software, including enabling ultrasound imaging and characterization (and various forms thereof), ultrasound-guided planning, and ultrasound-guided treatment, all in real time. The system may be configured to allow the user to image the patient manually, semi-automatically, or fully automatically (e.g., by hand or using a robot-controlled imager). In some embodiments, the robotic system may sweep the onboard ultrasound system across a target volume (e.g., linear sweeps and / or angled sweeps) to generate volumetric imaging data.

[0103]

[0122] The user may also be able to select, annotate, mark, highlight, and / or contour various regions of interest or treatment areas (on the image) and defined treatment targets, which can be used to command and instruct the system, via the system software, user interface, and display, where to image, test, and treat. Depending on the configuration, the user may use a manual ultrasound probe (e.g., a diagnostic handheld probe) to perform the procedure. In another configuration, the system may use a robotic and / or electromechanical positioning system to perform the procedure as directed and / or automated by the system, or conversely, the system may allow a combination of manual and automated use. The system may also include various settings or modes of display visualization mechanisms (e.g., marks, contours, and / or other overlays), including toggles on and / or off.

[0104]

[0123] The system may further include image registration capabilities, including imaging and image dataset registration, to enable the system to navigate and localize to a patient, including the treatment site (e.g., identification of tumors, vital structures, bone biostructures, biostructures and their features). In one embodiment, the system enables a user to image and identify a region of interest, e.g., the liver, using integrated ultrasound, and to select and mark tumors (or alternative markers) contained within the liver via / displayed in the system software, the system registers the image data to a coordinate system defined by the system, thereby further enabling the system's therapeutic and robotic components to deliver synchronized acoustic cavitation / historipsy to the marked tumor. The system may also include the ability to register various image sets, including those disclosed above, with each other, as well as providing navigation and localization (e.g., a therapeutic transducer to a CT or MRI / ultrasound fusion image, by having the therapeutic transducer and robotic components track to the above image).

[0105]

[0124] The system may also include the ability to operate in a variety of interventions, endoscopic and surgical environments (surgical / laparoscopic towers, visual systems, endoscopic systems and towers, ultrasound-enabled endoscopic ultrasound (flexible and rigid), percutaneous / endoscopic / laparoscopic and minimally invasive navigation systems (e.g., optical, electromagnetic, shape-sensing, ultrasound-enabled, etc.)), including alone and in conjunction with other systems, and these may also operate with or include various optical imaging capabilities (e.g., fiber and / or digital). The disclosed system may be configured to operate with these systems, and in some embodiments may operate in coordination with them, or in other embodiments, all or part of the system may be incorporated into the above systems / platforms (e.g., acoustic cavitation / histtripsy-enabled endoscopic systems or laparoscopic surgical robots). In many of these environments, therapeutic transducers may be used, for example, during or before / after the use of optically guided endoscopes / bronchoscopes, or, as an alternative example, when laparoscopic robots (e.g., intuitive da Vinci multi and single-port systems) are observing / manipulating tissue / treatment sites. Furthermore, these embodiments and examples may include cases where the other systems / platforms described above are used to deliver fluid (locally) to enable the formation of an artificial acoustic window, and the other systems / platforms may not be present under normal circumstances (e.g., fluidizing a segment or lobe of the lung in preparation for acoustic cavitation / histtripsy by non-invasive transthoracic treatment (e.g., the transducer is positioned outside the patient, above / around the patient)). The components disclosed herein may also include all or part of component hardware packaged within other systems (e.g., carts, computing devices, memory, etc.).

[0106]

[0125] The system may also be configured to display real-time visualization of bubble clouds in a spatial-temporal manner, including tissue effect pre- or post-treatment of the results of tissue-bubble cloud interaction, using various parameters as described above and other parameters, in which case the system can dynamically image, visualize, and display bubble clouds and changes to them (e.g., decrease or increase in echo intensity), which may include intensity, shape, size, location, form, persistence, etc. These mechanisms may enable the user to track and follow treatments sequentially in real time within a single integrated procedure and interface / system, and to verify the safety and effectiveness of the treatment on the fly (in contrast to other interventional or surgical modalities that require multiple procedures to achieve the same thing, or where treatment effects cannot be seen in real time (e.g., radiotherapy), or where it is impossible to achieve such a thing (e.g., real-time visualization of local tissue during thermal ablation), or where other procedures require invasive techniques (e.g., incision or puncture) and repetitive imaging in the scanner between procedure steps (e.g., CT or MRI scans)). The components, modalities, mechanisms, and workflows described above, as well as their usage methods, may be implemented in a non-limiting manner by implementing hardware, software, user interfaces, and usage environments, and future improvements, enhancements, and inventions in this art, along with the resulting data and means for analyzing such data, artificial intelligence, or digital health applications and systems, are deemed to be included within the scope of this disclosure.

[0107] software

[0126] The system may include various software applications, mechanisms, and components that enable users to interact with, control, and use the system for a wide range of clinical applications. The software may communicate with and collaborate with one or more components, including, but not limited to, therapeutic, integrated imaging, robotics, and other components, applications, and system accessories.

[0108]

[0127] Overall, in no particular order, the software provides mechanisms and support for planning procedures, including initializing and setting up the system, maintaining the system, transmitting and importing / exporting / storing data, modifying / operating / configuring / controlling / commanding various settings and parameters by the user, mitigating safety and user-related risks, transducers, robotic arms and drive systems, function generators and amplifier circuits / slaves, test and treatment ultrasound sequencers, transducer steering and positioning (electromechanical and electron beam steering, etc.), support for various configurations of treatment patterns, support for imaging and imaging probes, their manual and electromechanical / robot-controlled movement, and various dimensions within or around the procedure and treatment site (e.g., from one anatomical location to another). It can provide imaging support for measuring / characterizing depth (such as to the depth of the treatment site), pre-treatment evaluation and protocols for measuring / characterizing in-situ treatment site characteristics and conditions (e.g., acoustic cavitation / histtripsy threshold and its heterogeneity), targeting and target registration, calibration, marking / annotation, localization / navigation, registration, guidance, delivery and guidance through workflows, procedure steps, treatment plans and protocols, performed automatically, autonomously, and under direct observation and viewing with real-time imaging displayed by the software, including various views and viewpoints for viewing, communication tools (video, audio, sharing, etc.), troubleshooting, instructions, warnings, alerts, and / or enable communication via various network devices and protocols.Furthermore, the software user interface and the supporting display are expected to include a variety of buttons, commands, icons, graphics, text, etc., enabling the user to interact with the system in a user-friendly and effective manner, and these may be presented in an unlimited number of substitutions, layouts, and designs, and may include multiple displays (e.g., touchscreen monitors and touchpads) and / or may be displayed in similar or different sets of mechanisms for systems that can be networked to one or more external displays or systems (e.g., another robot, navigation system, system tower, console, monitor, touch display, mobile device, tablet, etc.).

[0109]

[0128] The software, as part of a typical system including one or more computer processors, can support various aforementioned function generators (e.g., FPGAs), amplifiers, power supplies, and therapeutic transducers. The software may be configured to allow the user to select, determine, and monitor various parameters and settings for acoustic cavitation / histtripsy, and to stop / start / modify the above parameters and settings as feedback on performance and conditions is observed / received.

[0110]

[0129] The software may be configured to support automatic detection of the transducers, after the user selects from a list or menu of multiple transducers and connects to the system (and verifies appropriate sequence and parameter settings based on the selected application). In other embodiments, the software may update targeting and amplifier settings (e.g., channels) based on a specific transducer selection. The software may also provide transducer recommendations based on pretreatment and planning inputs. Conversely, the software may issue an error message or warning to the user if the selection or parameters of the therapeutic transducer, amplifier, and / or function generator are incorrect and result in a malfunction or failure. This may further include reporting the details and location of the malfunction.

[0111]

[0130] In addition to the above, the software may be configured to allow the user to select treatment sequences and protocols from a list or menu, and to remember selected and / or previously selected sequences and protocols associated with a specific clinical use or patient profile. The associated profile may include any associated patient, procedure, clinical and / or engineering data, which may be used to notify, modify and / or guide current or future treatments or procedures / interventions, whether as decision support (e.g., using serial datasets to build and guide new treatments) or as an active part of the procedure itself.

[0112]

[0131] As part of the plan or during treatment, the software (and in cooperation with other components of the system) may enable the user to evaluate and test acoustic cavitation / histtripsy thresholds at various locations within a user-selected region of interest or a defined treatment area / volume, to determine the minimum cavitation threshold for the entire region or area / volume, and to ensure that treatment parameters are optimized to achieve, maintain, and dynamically control acoustic cavitation / histtripsy. In one embodiment, the system may enable the user to manually evaluate and test threshold parameters at various points. Threshold points may include defined boundaries of the selected region of interest and treatment area / volume, inside the boundaries, and central locations / positions, and the resulting threshold measurements may be reported / displayed to the user and used to update treatment parameters before treatment. In another embodiment, the system may be configured to enable automated threshold measurement and updating enabled by a robotic component, in which case the user may instruct the robot or command the robot to perform the measurements automatically.

[0113]

[0132] The software may also be configured to enable various substitutions for delivering and positioning optimized acoustic cavitation / histtripsy in and through a selected region / volume, in cooperation with a computer processor and one or more function generators, amplifiers, and therapeutic transducers. This may include, but is not limited to, systems configured with fixed / natural focus configurations using various combinations, including purely electromechanical positioning configurations, electron beam steering (with or without electromechanical positioning), electron beam steering to a newly selected fixed focus with further electromechanical positioning, axial (Z-axis) electron beam steering with lateral (X and Y) electromechanical positioning, high-speed axial electron beam steering with lateral electromechanical positioning, high-speed beam steering in 3D space, and dynamically changing one or more acoustic cavitation / histtripsy parameters (e.g., dynamically adjusting amplitude across the treatment region / volume) based on the ability to update therapeutic parameters based on threshold measurements.

[0114] Treatment patterns and routes

[0133] As part of a treatment plan, various treatment patterns and pathways may be used to position bubble clouds at one or more desired focal locations within a target tissue volume. Patterns may include one or more focal locations at specified locations in 2D and 3D space, including, but not limited to, configurable pattern variables, including location, spacing, and / or defined overlap (minimum and / or maximum) of the focal locations. This may further include grouping the focal locations into various desired shapes (e.g., columnar, elliptical, layered, etc.), in which case the shapes may be combined / placed into larger volumes. For example, an ellipsoidal volume consisting of radial layers (of combined focal locations), or, conversely, an ellipsoidal volume consisting of linear columns. Patterns may include non-limiting features and deformations, taking into account the size of the treatment volume, the morphology (size) and location (arrangement of bubble clouds / focal locations) within the treatment volume (centrally located, off-center, or various intercentral arrangements / orientations, etc.).

[0115]

[0134] The "path" can include various techniques for moving and transporting the bubble cloud through a selected or defined pattern. In some embodiments, this may include movement to the next nearest point in the pattern. In other embodiments, it may include movement to a preferred position in the plan at a distance from the current focal point (e.g., only two or more focal points away). Depending on the configuration, the path may include movement to the furthest focal point. The path may be configurable, for example, based on a desired cooling profile.

[0116]

[0135] Depending on the embodiment and system configuration, this may include a linear pattern and a path traversing the spherical treatment volume in a series of axial slices (parallel to the imaging plane) that start from the central slice within the treatment volume and proceed outward in the positive x-dimensional (relative to the transducer array) until the entire +x half of the spherical treatment volume is treated. The treatment then moves to an untreated slice adjacent to the center and treats the remaining half of the spherical volume, in this case proceeding outward in the negative x-dimensional. Within each slice, the treatment may start from the central point and move outward in a spiral.

[0117]

[0136] The "top-down" and "bottom-up" patterns and pathways differ from other linear patterns in that, rather than traversing the treatment volume in axial slices, the robotic system is configured to move the transducer array focus through the treatment volume in a series of lateral slices (i.e., slices perpendicular to the acoustic axis of the treatment transducer). Within each slice, treatment begins at the center and moves spirally outward (similar to how typical linear patterns traverse axial slices). As their names suggest, the "top-down" and "bottom-up" patterns traverse the lateral plane of the sphere, from the top (closest to the transducer) to the farthest (farthest from the transducer), or from the farthest to the top, respectively.

[0118]

[0137] In an alternative configuration, the pattern and pathway may include a fragmented target tissue volume divided into many slices, treated in an alternating order starting from the center of the volume (the numbers below each slice indicate the treatment order). Within each slice, columns are treated alternately (the numbers below each column indicate the treatment order). The columns themselves may be traversed top-down, bottom-up, and / or a combination thereof, depending on the type of treatment, the type of tissue, and the location of the tissue.

[0119]

[0138] Other patterns and paths may correspond to variations of these patterns. In one example, a spherical volume is still traversed in a set of axial slices parallel to the imaging plane, with the progression of treatment within each slice remaining the same. The only difference between these two methods is the order in which the axial slices are treated. Specifically, in one embodiment, the pattern and path treat the axial slices starting from one transverse end of the volume (e.g., the furthest slice in +x dimension) and proceeding through the slices one at a time until reaching the other transverse end of the volume (the furthest slice in -x dimension). In another configuration, the pattern and path increment through the slices in a strategic order chosen to maximize the spatial distribution / distance of consecutive treatment slices. If we define slice 0 as the slice along the central axis of the sphere, 6 as the furthest slice in +x dimension, and -6 as the furthest slice in -x dimension, then in this example, the treatment proceeds through 13 slices containing a 3cm sphere in the order of 0, 4, -2, -5, -1, 6, -3, 5, 1, -6, 3, -4, 2.

[0120]

[0139] In one example of a "spiral in-out" pattern and pathway, treatment is performed by traversing a spherical volume of a series of radial layers outward from the center of the sphere. Within each layer and when moving between layers, points are treated in order of proximity (i.e., the next treated point is the nearest untreated point in the current radial layer, or the nearest point in the next radial layer when moving between layers). Depending on the embodiment, the pattern can move in a spiral or annular motion throughout each layer. Once a given layer is completed, the pattern can move to the next layer, typically the nearest layer in its given direction of progression. The spiral patterns described herein can be treated from the most distal layer to the most proximal layer or vice versa (relative to the transducer).

[0121]

[0140] This also includes crossing patterns and pathway combinations. Specifically, a combination of "spiral in-out" and "bottom-up" is envisioned, in which the most distal layer is treated first, generally in a spiral pattern from the medial treatment point outward. Generally, the transition between layers is from distal to proximal, treating the medial treatment point first within each new layer before moving on to the lateral treatment point.

[0122]

[0141] In other examples, the size of cavitation or bubble cloud at a given focal point can be enlarged or enhanced by a rapid electronic steering technique that rapidly steers at or between multiple points intersecting a given focal point. This technique may be referred to herein as a “bubble saber.” A “bubble saber” or column-shaped tip effector can be implemented by rapidly electronically steering the bubble cloud focal point in any direction (e.g., z-direction, xy-direction in 3D space) through an enhanced volume of a treatment point and a defined steering distance, and optionally repeating this rapid electronic steering multiple times. Depending on the embodiment, this configuration may allow a user to manipulate the bubble saber position via robot and software to treat a defined treatment area. This may include treating tissue for applications that create a treatment surface (across organs and / or biostructures, e.g., fissures, organ segment boundaries and / or desired excision surfaces, etc.). In some cases, this may be enabled as a linear tip effector (z-axis only). In other configurations, including those that enable 3D electronic steering, the tip effector may include non-linear shapes (e.g., arcs).

[0123]

[0142] The "bubble saber" technique can also offer significant thermal advantages by electronically steering the bubble cloud to a position closer than the geometric focus for ablation of shallower targets. The primary thermal advantage of the "bubble saber" technique stems from the electronic steering itself (the use of the lowest possible effective f-number). Another advantage of the "bubble saber" is the reduced effect of motion on local dose and the potential effectiveness of a more parallel treatment strategy (providing some protection to untreated tissue volumes, which move or shift to previously treated areas as a result of treatment in surrounding areas, thereby escaping further treatment). Depending on the embodiment, the "bubble saber" may include a linear tip effector, and depending on the configuration, it may include an arc-shaped or curved tip effector based on the desired treatment plan / plane.

[0124]

[0143] In another embodiment, histotripsy treatment can be applied in a "radial spiral" pattern that minimizes the distance between treatment columns while maintaining "inside-out" breakdown in the tissue. Instead of columns of treatment points arranged in a Cartesian grid of locations, the treatment points in this technique are arranged in radial layers. These layers are then treated from the inside out, with columns within each layer treated sequentially around each ring of the spiral (or alternately laterally if it is necessary to retain the thermal advantage of sequentially treated columns as far apart as possible). This pattern results in a more consistent cloud overlap in three dimensions and minimized distances between sequentially treated columns compared to linear treatment patterns, resulting in a planned ablation volume that more closely matches the ellipsoidal planned contour.

[0125]

[0144] This radial helix technique allows for flexibility in reducing treatment time by effectively eliminating the cooling time required when moving between spatially separated treatment columns. While this pattern does not eliminate the need for cooling time entirely, it offers the flexibility to include or exclude only the amount of cooling time required by the expected thermal load, i.e., the option to proceed faster when thermally acceptable. The radial helix can proceed in either a clockwise or counterclockwise direction.

[0126]

[0145] Planned bubble cloud therapy treats a specified percentage of the target tissue volume. In some cases, it is desirable that the selected pattern completely or nearly completely cover the entire tissue volume. In some embodiments, the pattern may be implemented to cover 90-100% of the target tissue volume. In other examples, it may be desirable to treat only 50% or less of a given volume. The amount or percentage of treatment may depend on the type of tissue, the location of the tissue, etc. The focal point center of each bubble cloud can be dispersed at discrete intervals in X and Y, ignoring any points outside the tissue volume boundary. The point position in Z can also be dynamically adjusted to match the contour of the tissue volume boundary. The spacing between adjacent focal points can be adjusted to determine the amount of overlap between focal points, if any. In one example, the focal point center for each bubble cloud can be dispersed in X and Y in a radial layer, with the radius adjusted to match the target tissue volume boundary. The focal point position in Z can also be dynamically adjusted to match the contour of the target tissue volume boundary.

[0127] Threshold Test

[0146] As described above, the system described herein includes the ability to evaluate and test acoustic cavitation / histtripsy thresholds at various locations within a user-selected region of interest or a defined treatment area / volume, to determine the minimum cavitation threshold throughout the entire region or volume, and to ensure that treatment parameters are optimized to achieve, maintain, and dynamically control acoustic cavitation / histtripsy. During treatment planning or treatment, cavitation threshold test pulses may be sent to multiple locations of interest. The number of test locations of interest may be selected based on the size and / or shape of the treatment area. For example, a spherical treatment area would benefit from at least seven test locations to probe the edges of the spherical volume, and these test locations may include the center of the treatment area or volume, and axial endpoints where the X, Y, and Z axes intersect the boundaries of the treatment area or volume, respectively.

[0128]

[0147] During treatment, the cavitation threshold at each site of interest is evaluated using a series of test pulses at an initial drive voltage and pulse repetition frequency (PRF) to determine if cavitation has formed. The drive voltage can then be incremented, or the PRF can be incremented to the next PRF. PRF can be defined as the number of pulses delivered per second by the system described herein. PRF can be adjusted during treatment depending on the cavitation threshold, tissue type, depth, etc. Cavitation formation (or non-formation) can be observed in real time using imaging, such as ultrasound imaging. Generally, the drive voltage required to generate an active bubble cloud in the tissue decreases as the PRF increases. The cavitation threshold in the tissue may also change as the treatment procedure progresses. Therefore, testing various points of interest within the treatment volume for treatment can be a useful means of evaluating the cavitation threshold and adjusting the PRF or drive voltage of the treatment pulse to optimize treatment at each site being tested. Next, the treatment protocol itself can be adjusted based on the test pulse to use a variable drive voltage or PRF based on the test results, in order to ensure that the optimal amount of energy is delivered to each location in the tissue for histotripsy treatment. Furthermore, the depth at each test site can be measured or determined (manually or automatically by the system) to provide the system with additional information for determining the optimal treatment parameters.

[0129]

[0148] In some embodiments, a test site may be used to determine the maximum amount of energy that can be applied without causing undesirable damage to the test site or surrounding or intervening tissue. For example, the system's drive voltage or PRF can be increased until cavitation is observed under real-time imaging and / or other feedback mechanisms, while determining the cavitation threshold at each test site. In some embodiments, the drive voltage or PRF can be increased until undesirable damage to the test site or cavitation, or thermal damage to another location outside the test site, is observed. This can be used to determine the maximum amount of energy that can be applied to a given test site.

[0130]

[0149] Based on the test protocol and the tested cavitation threshold, an appropriate drive voltage can be selected for each point in the treatment grid. Using the required voltages at the center and six endpoints of the target volume, which act as inputs, the voltages for the remaining points, including the treatment volume, can be interpolated. The drive voltage can then be automatically adjusted by the software as the treatment progresses through the automated treatment volume. In this way, each point is ablated using an amplitude that is sufficient to maintain an effective bubble cloud but not excessive to minimize heat buildup in the acoustic path.

[0131]

[0150] For example, a method for delivering histotripsy therapy to tissue may include delivering histotripsy pulses to tissue at multiple target test sites and imaging the test sites in real time to assess whether cavitation has formed at each test site. If cavitation has not formed at a test site, the driving voltage or PRF of the histotripsy pulse can be adjusted, and the histotripsy pulse with the adjusted parameters can be delivered into the tissue at the test site. Real-time imaging may also be used in this case to assess whether cavitation has formed at each test site. This process can be repeated until a cavitation threshold at each test site is determined, and a high-density map may be created based on various algorithms to extrapolate thresholds across the entire target region / treatment volume of interest, which are specific to the acoustic pathway and target depth. For example, if the cavitation thresholds at a first and second test site are known, the cavitation threshold at a third test site can be extrapolated based on the cavitation thresholds at the first and second test sites. This extrapolation may further be based on the type of tissue, target tissue depth, and acoustic pathway at the third test site.

[0132] Therapeutic pulse sequencing and temperature control

[0151] A given histotripsy treatment or treatment session can be defined in terms of the set number N of pulses delivered over a set total treatment time T. Thus, the total number N of pulses delivered over a total treatment time T (in seconds) is equal to the total treatment time T multiplied by the system's PRF. For example, a system operating with a constant 200 Hz PRF over a total treatment time of 10 minutes (600 seconds) will have a total pulse number N equal to 120,000. The systems and methods described herein may include PRFs of 400 Hz or higher, including PRFs in the range of 400–900 Hz, to induce acoustic cavitation. For example, if a 200 Hz PRF is used, the treatment may be applied over 10 minutes.

[0133]

[0152] This specification provides systems and methods for implementing histotripsy pulse sequences, which have a hypothetical case of N pulses evenly distributed over a treatment time T, having frequent, short cooling periods that favorably enhance the temperature profile generated by histotripsy treatment, resulting in a minimum temperature rise. These pulse sequences can further be characterized in terms of the length of time the treatment is actively delivered to the tissue relative to the length of cooling periods during which the treatment pulse is not delivered to the tissue. For example, a system that delivers treatment pulses at a 400 Hz PRF for 5 minutes, followed by a 5-minute cooling period during which no treatment pulses are delivered (total treatment time of 10 minutes), would have a 1:1 treatment (5 minutes) to cooling (5 minutes) ratio. The PRF can be adjusted to any frequency between 200 and 900 Hz, and as the frequency of the PRF increases, larger and more frequent pauses in energy application may be employed. For example, at a 400 Hz PRF, 2.5 minutes of treatment may be applied, followed by 2.5 minutes of cooling until a total of 10 minutes of treatment is achieved.

[0134]

[0153] Generally, when the therapeutic PRF is doubled and cooling steps are given, the degree of temperature rise depends on the distribution of the cooling steps. A single long cooling step can produce the maximum temperature rise observed with this strategy. Conversely, shorter / more frequent cooling steps approach the case of evenly distributed pulses and produce the minimum temperature rise observed with this strategy. Also, within a given total therapeutic time window, a higher therapeutic-to-cooling time ratio (e.g., 3:1) is generally more favorable than a lower therapeutic-to-cooling time ratio (e.g., 1:3). Essentially, a lower PRF is thermally advantageous for the number of histotripsy pulses delivered within a given time window.

[0135]

[0154] Further details and examples regarding the duration of treatment, PRF, treatment time, cooling time, and other factors are described in detail in WO2021 / 258007, filed on 18 June 2021, entitled "HISTOTRIPSY ACOUSTIC AND PATIENT COUPLING SYSTEMS AND METHODS," which has been assigned to the assignee of the present invention, and its entire contents are incorporated herein by reference.

[0136]

[0155] When histotripsy is used to ablate a target volume larger than the cavitation bubble cloud formed by the system, the cavitation focus of the histotripsy treatment system is moved (mechanically or electronically) within the target volume to ablate the entire target volume. In the context of this disclosure, mechanical movement may include moving the physical position of the treatment head and / or treatment focus by a robotic positioning arm. Electronic movement of the focus, on the other hand, is achieved by electron beam steering of the focus by a transducer array. In some embodiments, the focus can be electronically beam-steering without moving the physical position of the transducer array. In some embodiments, mechanical movement is combined with electron beam steering. This disclosure describes methods, workflows, and techniques for realizing histotripsy treatment.

[0137] Histotripsy system

[0156] Figure 1A shows a robot-controlled histotripsy system 10 according to the present disclosure, specifically a robot-controlled histotripsy system configured for planned and automated treatment of patient tissue. The histotripsy system 10 includes a cart 12 housing a histotripsy signal generator and a control computing device (not shown). A robotic arm 14 extends from the cart 12, and a treatment head 20 including a treatment transducer 18 and an imaging probe 22 (Figure 2) is connected to the distal end of the robotic arm 14. The robotic arm 14 includes an arm interface 16 (Figure 2) that enables connection of the treatment head 20 to the robotic arm 14. A user interface display 24 mounted on the cart 12 is configured to present one or more user interfaces (UIs) and to connect to a control computing device (not shown) to enable the workflows described further herein in relation to Figures 3A to 15 and Figures 17 to 50 below. An ultrasound imaging system 26 is connected to the treatment head 20 and specifically to the imaging probe 22 (Figure 2) to display ultrasound images during all or part of the procedures described below in this specification. The user interface display 24 includes various input points, including physical controls such as knobs or buttons 28 for adjusting the planned treatment volume, contour, target, margin, and depth of focus in the X, Y, and Z directions, as described below; an emergency stop button 30; a voltage knob 32 for adjusting, starting, and stopping the application of voltage to the treatment transducer 18; a trackpad 34 for making selections and operating aspects of the user interface; and a space mouse 36 for driving the robotic arm 14 and the treatment head 20 using the robotic drive mechanism of the robotic arm controller. The UI display 24 may also be a touchscreen device capable of receiving user input to various UI screens displayed on the UI display 24 and to the workflow described herein.User input may include direct input or manipulation via a touchscreen-enabled UI, or it may include physical manipulation of the knob 28 and space mouse 36 interacting with the UI, or a combination of these types of inputs. Other forms of user input may also be acceptable and within the scope of this disclosure, including but not limited to mobile devices such as tablets, smartphones, smartwatches, smart glasses / goggles, and virtual reality (VR) devices or systems.

[0138]

[0157] Figure 1B is another diagram of the histotripsy system 10, including a cart 12, a robotic arm 14, and a treatment head 20. Figure 1B also shows an ultrasound imaging system 26 that may be electrically coupled to the cart 12 to supply ultrasound images to the cart and associated controller / processor. As shown, the cart 12 may include a user interface or display 24, and the ultrasound imaging system 24 may also include a user interface or display 27.

[0139]

[0158] Figure 1B also shows a fluid cart 29 configured to fill the coupling system / container with an acoustic coupling medium for coupling a therapeutic transducer / treatment head to a patient. For simplicity, the coupling container is not shown in Figure 1B.

[0140]

[0159] The histotripsy system 10 is configured to be used in conjunction with a separate imaging system such as ultrasound, MRI, or cone-beam CT to provide real-time and / or perioperative imaging during histotripsy treatment. As shown in Figures 1A and 1B, the histotripsy system 10 may be configured to be used in conjunction with a separate ultrasound imaging system 26. This separate ultrasound imaging system 26 provides real-time visualization and can be used as needed during patient setup, localization, planning, or any point postoperatively. The separate ultrasound imaging system 26 includes freehand ultrasound and is also connected to a built-in ultrasound imaging probe configured within the treatment head 20. Specifically, the histotripsy system 10 is positioned on a first side of the patient (e.g., the patient's right or left side), as shown in Figure 1B, and the separate ultrasound imaging system 26 is positioned on a second, opposite side of the patient (e.g., the patient's left or right side). It may be preferable for the histotripsy system 10 and the separate ultrasound imaging system 26 to be positioned on opposite sides of the patient for a better surgical workflow.

[0141]

[0160] Figure 2 shows an enlarged view of the treatment head 20, including the treatment transducer 18. The treatment head 20 is configured to interface / connect with the robot arm interface 16 at the distal end of the robot arm 14, and to allow for rapid on / off switching to further enable the use of multiple treatment heads (and treatment configurations) on / with the histotripsy system 10. For example, it is envisioned that different shapes or sizes of treatment heads 20 may be used when targeting treatment volumes and depths within the brain compared to abdominal locations such as the liver or kidneys. Specifically, when a patient is being treated at various locations and depths within the body, rapid connection / disconnection can enable reduced procedure time in the operating room. As described above, the treatment head 20 includes the treatment transducer 18 and a separate ultrasound imaging probe 22. The imaging probe 22 is directly connected to the ultrasound imaging system 26 on a UI display 24 associated with the ultrasound imaging system 26. Furthermore, the ultrasound imaging system 26 is connected to a control computing device in the cart 12 so that the output from the imaging probe 22 can also be viewed on the user interface display 24. The imaging probe 22 is configured to translate (extend) beyond the therapeutic transducer 18 by rotating the dial 38. In Figure 2, the imaging probe 22 is shown in the retracted position. An orientation and rotation tab 40 is operably connected to the imaging probe, allowing for a 90-degree rotation of the imaging probe 22 relative to the therapeutic transducer 18. A handle 42 allows for grasping the treatment head 20 and manual and / or robot-assisted movement. Free-drive buttons 44 are located on the top surface of the handle 42. When at least one of the free-drive buttons 44 is pressed by the user, it substantially disconnects the resistance provided by the motor and gear mechanism of the robot arm 14, but maintains sufficient resistance to prevent the robot arm 14 from falling when the free-drive buttons 44 are pressed.In this way, the handle 42 and the free-drive button 44 enable load-compensated positioning of the treatment head 20 and the robotic arm 14.

[0142]

[0161] Figure 3A provides a broad overview of the steps employed in performing the histotripsy treatment workflow 50. The workflow is primarily guided by a software application running on a control computing device. In one exemplary implementation, the workflow begins with initial setup in step 52, where the software performs self-tests to ensure that key aspects of the histotripsy system 10 are accessible and properly configured for the session. After initial setup, the user must log in in step 54. In step 56, system setup is performed, as described below in more detail with reference to Figures 4-6. Following system setup, a system check is performed in step 58, as described below with reference to Figures 7A-10C. Following the system check, patient registration takes place in step 60, which is described below in more detail with reference to Figures 11-12. Patient registration involves generating a new patient record in step 61 or opening an existing patient record as shown in Figure 13. From the opened or new patient record, a treatment session consisting of localization, planning, and treatment can be initiated. Next, the localization process in step 63 is performed, which involves patient preparation in step 64 and treatment head 20 buoyancy calculation or resistance detection in step 66, as detailed with reference to Figures 14-22. If the fusion skip option 70 is selected following the resistance detection calibration in step 66 (for example, button 503 as shown in Figure 24), the workflow immediately proceeds to the treatment planning step 80. If fusion is desired, the workflow proceeds to the capture of a robotic ultrasound sweep of the patient and specifically the target area in step 72, as detailed with reference to Figures 24-27. Following the ultrasound sweep, initial orientation is performed in step 74 (Figure 28) by identifying markers in the ultrasound images and the preoperative or perioperative image dataset, which may have been selected in the patient registration step in step 60 above, and initial orientation is formed by fusing the ultrasound images from the robotic sweep with those of the preoperative or perioperative images.Once the initial registration is reviewed, adjusted, and accepted as described in step 76 with respect to Figures 28–32, the live ultrasound image is fused with the preoperative or perioperative image in step 78. Next, in step 80, as described in respect to Figures 34–40, the live fused image or simply the live ultrasound image is used to identify the biostructure to be treated, which includes the treatment contour and margins around the treatment contour, and further includes ensuring that the sound field 712 defined by force lines 724 can be used to avoid or take into account treatment through bone, gas portions of the intestine, or other parts of the biostructure that may absorb histotripsy pulses and limit the effect of any part of the treatment. The planning step also requires navigation to the edge regions of the volume to be treated so that the robotic arm 14 and treatment head 20 can be reliably navigated to the desired location in the patient's body without violating a threshold of resistance to movement. Furthermore, planning includes navigating to the highest point in the treatment volume (the most distal to the patient) to ensure that there is sufficient binding medium to complete the treatment. As part of the plan, the user is also required to mark the location of the muscle / fat layer above the target biostructure, which is used as input to the automated treatment algorithm. After the plan is complete, the workflow proceeds to treatment step 82. Treatment 82 includes step 84, where the focus 726 is calibrated to the bubble cloud location, and then, as the robotic arm 14 and treatment transducer 18 navigate to the location on the body, the voltage required to generate a bubble cloud is established at each of several survey points 739 so that the application of its histotripsy energy reliably generates a bubble cloud 1108 at the focus 726, as described in relation to Figures 42-50. Furthermore, it is confirmed that the focus 726 and the bubble cloud are located near the center of the volume defined by each of the treatment contours 728 and margins 732 of the survey points and those survey points 739. Once acceptable, automated treatment in step 86 is performed, in which a series of focus locations are treated individually with histotripsy pulses, as described in relation to Figures 46-50.The volume to be treated consists of multiple such focal locations that may be arranged in an overlapping manner. The robotic arm 14 moves the therapeutic transducer 18 robotically along the outside of the patient (ensuring that the resistance threshold is not violated) until all planned focal locations receive a histotripsy pulse. After all focal locations have received a histotripsy pulse, the treatment may be reviewed using the ultrasound imaging probe 22, either by manually using the free-drive button 44 to drive the robotic arm 14 or by electronically using the space mouse 36. Following the review, the treatment session ends in step 88, or the process returns to step 61 so that a new treatment session may be started. As described above, this is a schematic description of the process, and further details are provided below along with the relevant diagrams.

[0143]

[0162] While the embodiments of workflow 50 have been outlined, each of these embodiments will be described in more detail, starting with Figure 3B. Figure 3B is a flowchart outlining the method 100 for initial setup and configuration of the histotripsy system 10 according to this disclosure. In step 102, after powering on the histotripsy system 10, the software is initialized, which optionally may require the input of login credentials to a computing device housed in the cart 12. After initialization, the software performs a connection check in step 104, and the results are displayed in a callout box 202 (Figure 4) on the user interface 200. As can be seen in Figure 4, the connection check attempts to verify that the robotic arm 14, the control panel (e.g., display 24 and input devices 28-36), the therapeutic generator (not shown but housed in the cart 12), a separate ultrasound system 26, and the treatment head 20 are connected to the computing device (not shown but housed in the cart 12). The connection check also attempts to verify that the robotic arm 14 is in the "standby position". If the ultrasound system 26, control panel, therapeutic generator, or robotic arm 14 is not connected, in step 106 the user connects these devices as needed, and the connection check will update the status accordingly. With respect to the therapeutic head 20, the record of the last calibration is displayed in the speech bubble box 204, in which button 206 enables the start of calibration, and a second button 208 enables the change of therapeutic head 20.

[0144]

[0163] Regardless of whether the treatment head 20 is attached or not, the user is instructed to press and hold the standby position button 210 (Figure 4) in step 108 to signal the robot arm 14 to drive to the standby position. After the robot arm 14 is in the standby position, the next button 212 becomes available, and when selected, the user interface 200 changes to display the system setup screen on the UI 200, as shown in Figure 5A. The system setup screen provides instructions for attaching the treatment head 20 (if necessary) in step 110, connecting the I / O cable 45 from the treatment head 20 to the robot arm 14, supplying information on the position and orientation of the imaging probe 22 (if necessary), and checking the treatment transducer 18 for cracks or other defects.

[0145]

[0164] The selected treatment head (and associated identification data) may be relayed to the histotripsy system via a hardware / software interface or may include built-in configuration information (and files) as input. Specifically, a memory board in the transducer ZIF connector communicates with a ZIF board in the generator. Other forms of cables and wireless communication may also be used to share information between various system components. Information may be exchanged between the transducer and the generator. System information that may be exchanged between the treatment head / therapeutic transducer and the rest of the system (e.g., generator) may include, but are not limited to, the model number, serial number, number of transducer elements, depth of field / focal length, thermal offset coefficient, detailed specifications of the therapeutic transducer including element timing calibration, indication of application (anatomical site, organ, disease, etc.), software page to call, details of use case (e.g., ultrasound-guided or CBCT-guided), payload, different treatment sequences, bubble cloud location, imaging plane calibration matrix, expected bubble cloud size, workflow details including expected voltage and total runtime for obtaining bubble cloud in water performance, and / or maintenance-related data including system check calibration data (if calibrated within the last 24 hours / historical calibration data), manufacturing date, and time until service. The treatment head connection may also include the connection of a ZIF cable to the cart / generator and other I / O connections to one or more robotic arm configurations and / or imaging systems (ultrasound, X-ray, etc.).

[0146]

[0165] After completion, following the selection of the Next button 214, the UI200 displays the screen shown in Figure 5B, on which the user is prompted to select the serial number of the connected treatment head from the drop-down list 213. Once the serial number is selected, the date and time of the last valid calibration, which is part of the system check, is displayed, and the Next button 215 becomes available. This information is also available in the treatment head menu 217 in the upper right corner of the screen. Following the selection of the Next button 215, the UI200 displays the screen shown in Figure 6, on which the user is prompted to confirm that the ultrasound imaging system 26 is outputting a signal to the computing device on the cart 12, so that the signal from the imaging probe 22 is displayed on the UI200 in step 112. Text on panel 216 may be used to instruct the user to confirm that the imaging settings of the ultrasound imaging system 26 are optimized for use with the histotripsy system 10.

[0147]

[0166] Following the selection of the Setup Complete button 218, the workflow proceeds to the system check phase (e.g., step 58 in Figure 3), and the UI 200 displays the screen shown in Figure 7A. The histotripsy system 10, and specifically the treatment head 20, requires one calibration within a 24-hour period, but multiple procedures are often planned within a given day, and the treatment head 20 may have already been calibrated and mounted on the robotic arm 14, as indicated by the callout box 202. If a system check has been performed within the last 24 hours, the results are still valid, and there is an option to “skip system check” and proceed directly to the patient registration phase (e.g., step 60 in Figure 3). Depending on the environment, a system check may be performed at the start of each day, before any histotripsy treatment procedure. A system check may also be performed if the location of the histotripsy system is physically moved to a new or different location, for example, from one operating room to a different operating room.

[0148]

[0167] If a system check is required, step 114 is performed, where the UI200 displays instructions to fully extend the imaging probe 22 and rotate the imaging probe 22 to the +X position. The actual position and orientation of the imaging probe 22 relative to the therapeutic transducer 18 is constantly calculated using signals transmitted via the I / O cable, which are interpretable by the software. After the imaging probe 22 has been moved to the required position as indicated by the imaging probe orientation and position indicator 219, the confirm button 220 is selected. When button 220 is selected, the software compares the actual position and orientation signals to the expected signal range, and if the actual signals are within the expected range, the workflow proceeds to the screen shown in Figure 7B of the UI200. The workflow then requires the imaging probe 22 to be rotated back to the -Y position and retracted into the therapeutic transducer 18, which may be referred to herein as the “home position”. In this case as well, when the confirm button 221 is selected, the software compares the actual position and orientation signals to the expected signal range, and if the actual signals are within the expected range, the workflow proceeds.

[0149]

[0168] Following the selection of the confirmation button 221 in UI200 in Figure 7B, the workflow proceeds to UI200 shown in Figure 8, where instructions are displayed in panel 216 to fill the fluid container with the ultrasonic medium and to submerge the treatment head 20 into the fluid container to the minimum fill line in step 116. When the treatment head 20 is submerged in the ultrasonic medium, an ultrasonic image will appear on UI200 as shown in Figure 9. The fluid container may optionally circulate the ultrasonic medium to remove / reduce gas and regulate temperature before submerging the treatment head.

[0150]

[0169] As shown in Figure 9, a resistance indicator 222 is displayed as a boundary at the bottom of the UI 200, which indicates the resistance to movement the treatment head 20 experiences when it is pressed into the ultrasonic medium, although at this point in the process the resistance has not been calibrated to take into account the buoyancy of the treatment head itself. Details of that calibration process, which is performed before treatment, are described below. The resistance indicator 222 is a safety mechanism for the navigation of the treatment head, for the precise positioning of the treatment within the patient, and for other aspects of this disclosure. The resistance indicator 222 may be indicated as a color indicator such as yellow, orange, or red, corresponding to a preset value that can be read as “low,” “medium,” or “high” resistance in the UI. Other resistance indicators are also included in the scope of this disclosure and may be presented to the user on the UI or elsewhere on the console or cart. Alternatively, the resistance indicator may be an auditory, tactile, or other visual indicator to the user.

[0151]

[0170] Following the selection of the Next button 224 in Figure 9, Method 100 initiates a calibration process for the therapeutic transducer 18. This calibration process is intended to align an indicator to the location of the therapeutic focus (e.g., the center of the bubble cloud) formed by the therapeutic transducer 18. As shown in Figure 10A, the user is instructed to activate the therapeutic output in step 118 by selecting button 226, and then to press the voltage knob 32. The therapeutic output is then increased by turning the voltage knob 32 until the bubble cloud 228 is visualized. The bubble cloud 228 may be visualized when the voltage knob is at approximately 18-24% in the case of degassed water (e.g., an ultrasonic coupling medium). In step 120, the trackpad 34 is used to mark the center of the bubble cloud 228 by indicator 230. This visualization may be accompanied by the user detecting an audible signal (e.g., frequency or volume) within a given range that indicates the formation of the bubble cloud. As can be seen by comparing Figure 9 with Figures 10A to 10C, the voltage indicator 232 is lit and rises to indicate 21% and 22%. After the bubble cloud 228 is marked by the indicator 230, the offset distance, specifically the distance the indicator 230 needed to be moved to be centered on the bubble cloud 228, is displayed on the panel 216 in the UI 200, as shown in Figure 10B. The voltage knob 32 may be pressed again to stop the treatment output in step 121. As shown in Figure 10C, if all values ​​are within an acceptable range and the treatment output is stopped, the confirm button 238 can be selected in step 122, completing the setup and calibration workflow; otherwise, the method can proceed to step 124, where the treatment head 20 is removed from the ultrasonic medium, then return to step 110, where the treatment transducer 18 is inspected, and the method is repeated. Alternatively, method 100 may return to step 118, restarting the voltage knob 32 and making a new attempt to mark the center of the bubble cloud 228 within the offset limit.Naturally, if calibration has been completed within the last 24 hours, one or more steps of the setup and calibration steps may be omitted without departing from the scope of this disclosure.

[0152] Patient registration and patient records

[0171] Following setup and system checks, the UI200 proceeds to the screens shown in Figures 11 and 12, allowing the user to select one or more image recordings of a patient. These image files, which may be ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), cone-beam CT (CBCT), and / or positron emission tomography (PET-CT) images, may be imported from an electronic medical record (EMR) database, PACS system, USB drive, cloud-based information or storage system, or stored in memory associated with the computing device of cart 12. Depending on the embodiment, for example, in the case of a procedure performed by a fixed room or mobile CBCT imaging system, the imaging system may function as a DICOM node for a histotripsy system, enabling direct transfer of images and data between both systems for the use of preoperative, perioperative, and postoperative images. Depending on the system, these images / data may be used to enable multimodal imaging localization and targeting, or conversely, perioperative identification of treatment site or treatment tissue effect, and / or postoperative verification of treatment effectiveness. By navigating the UI200 and inserting a patient ID or name in Figure 11, image files may be displayed as shown in Figure 12. These image files may then be displayed and / or used in the fusion process described herein so as to assist in guiding the application of treatment to the patient by the therapeutic transducer 18, as outlined below, during histotripsy treatment. Even if fusion is not performed, previously acquired images may be displayed in one or more areas of the UI described herein to assist in guiding the user to the appropriate location or application of the appropriate treatment. As shown in Figure 11, this import process may be skipped entirely. In this case, the user is given the option to enter new patient details to create a new patient record or to open an existing patient record.Depending on the embodiment and system configuration, the image files displayed on the system may include, but are not limited to, a variety of mechanisms, including organs, tissues and / or disease classifications, pre-planned treatment plan overlays, simulated treatment head pose markings, and / or other computer vision-enabled mechanisms to assist in the treatment planning stage.

[0153]

[0172] Following the selection of an image file and the selection of the Next button 240 or the Import Skip button 242, the UI 300 (Figure 13) is displayed on the user interface display 24. If an image file was selected, the reference image is displayed in the viewer as shown in Figure 13 by fields 302 and 304, and the reference image can be adjusted to display different imaging orientations or planes (e.g., axial, sagittal, coronal, and other projections) selected by button 305. The file name and other information of the selected reference image are displayed in a separate panel 306. The file name represents a patient record file under which any records of treatments applied to the patient will be stored for later review and evaluation. In addition, a live ultrasound image may be displayed in field 308 by selecting button 310. Button 312 can be selected to start or add a treatment session.

[0154] Localization

[0173] Figure 14 shows Method 400 detailing the steps taken to prepare the patient and the Histotripsy System 10 equipment for a treatment session, starting in step 402 by selecting the Add Session button 312 in Figure 13. Following the selection of the Add Session button, UI 300 updates panel 306 to display instructions as shown in Figure 15. Among these instructions is to use the ultrasound imaging system 26 and its ultrasound imaging probe (e.g., freehand) to capture the ultrasound image displayed in field 308 in step 406. The image captured (freehand) by the ultrasound imaging probe separate from the ultrasound imaging probe 22 incorporated into the treatment head 20 is displayed in field 308 on both the display associated with the ultrasound imaging system 26 and the UI display 24. The imaging in steps 404 and 406 ensures that the treatment site, which may have been identified in the preoperative images, is still the treatment site of interest and has not changed or been altered between the time of the patient's initial diagnostic scan and the day of the procedure. The instructions further in step 408 to optionally mark the location on the patient where the ultrasound probe of the ultrasound imaging system 26 will be placed, or where the lesion or tumor of interest is located within the patient's body wall cavity, so that the treatment area (e.g., lesion or tumor) can be visualized in the ultrasound image. To assist in the localization and imaging of the lesion so that the patient can be marked, the user can refer to the images displayed in fields 302 and 304. This marking further indicates the point where the treatment head 20 and / or coupling assembly 46 will be first positioned so that the imaging probe 22 can be used to visualize the treatment area. Therefore, the positioning of this mark should ensure that the optimal route for the application of histotripsy treatment is first identified. It may be advantageous to reduce the application of ultrasound energy through hard tissue, areas of intestinal gas, or other features that may affect the application of ultrasound energy to the treatment area.Once the visualization is complete, selecting the "Next" button 314 advances the workflow and displays the UI 300 as shown in Figure 17.

[0155]

[0174] Figure 16 shows the treatment head 20 as it is being used to plan and apply treatment to a patient. The treatment head 20 is inserted into a binding medium contained in a binding assembly 46, which enables acoustic coupling of the treatment transducer 18 with the patient. The binding assembly 46 includes a conformal, flexible barrier film or membrane 48 that allows the binding medium to be contained within the binding assembly 46 in a state that enables proper ultrasonic coupling between the treatment transducer 18 (and imaging probe 22) and the patient, according to the patient's shape and biostructure. Bed rail clamps (not shown) are fixed to the side of the treatment bed and also support the binding assembly 46. Naturally, when filled with 12-25 liters of binding medium, the binding assembly becomes quite heavy and requires support to minimize impact on the patient while still allowing sufficient coupling.

[0156]

[0175] As shown in Figure 17, panel 306 is updated to provide instructions for assembling the bed rail clamp and binding assembly 46 and for positioning it over the patient. The instructions also provide guidance for filling the binding medium into the binding assembly 46 and for eliminating air pockets between the film or membrane 48 and the patient. For example, specifically, the patient needs to have body hair removed from intervening external tissues (e.g., the abdomen) so that the number of hair follicles in contact with the air pockets is minimized. Selecting the Next button 316 advances the workflow to Figures 18 and 19, where buttons 318 and 320 change the image displayed in field 302 so that it shows an image 322 of the histotripsy system 10 in one of two different patient orientations or room setups in step 412. This selection of orientation is employed to provide orientation information that is taken up by the robotic arm 14 and software to drive the robotic arm 14 to perform image capture by the imaging probe 22 and the application of treatment by the therapeutic transducer 18. One aspect of this orientation is defining which is the Y+ direction and which is the Y- direction, as can be seen by comparing Figures 18 and 19. After selecting either button 318 or 320 to define the orientation of the histotripsy system 10 and other setup aspects such as locking the cart 12 or bed, or setting the bed height, the next button 324 can be selected. Alternatively, the patient orientation may be selected later during the localization phase of the histotripsy setup.

[0157]

[0176] Selecting the Next button 324 advances Method 400 to calibration step 414 as shown in Figure 20. In step 416, the Treatment Head Leveling button 326 can be selected, thereby causing the robot arm 14 to drive the treatment head 20 so that it is in a horizontal position (for example, parallel to the surface of the binding medium in the binding assembly 46). Following the leveling of the treatment head 20, the Next button 328 can be selected, and the workflow advances to Figure 21, where the UI 300 is updated so that panel 306 instructs the treatment head to move until the distal end of the treatment head 20 (distal to the user) is just touching the surface of the binding medium in the binding assembly 46, as shown in the instruction image in panel 306 of Figure 21. The treatment head 20 may be moved using, for example, the space mouse 36 in step 418. During this step, the system 10 can automatically disable the rotation of the robot arm 14 so that the treatment head 20 remains horizontal to the surface of the binding medium. After the treatment head 20 is positioned in step 418 so that its distal end or edge is in contact with the binding medium, you can select the next button 330 and proceed to the workflow shown in Figure 22.

[0158]

[0177] Selecting the Next button 330 at the end of step 418 sets a reference point for the software application to calculate the buoyancy of the treatment head 20. This buoyancy is subtracted from the force measured by the robotic arm to accurately determine the actual force applied to the treatment head 20 throughout the rest of the procedure. As shown in Figure 22, in step 420, the UI 300 updates panel 306 to instruct the UI 300 to submerge the treatment head 20 to a point where at least the surface of the binding medium is above the (marked) minimum fill line on the treatment head 20. As can be seen in Figure 22, a live ultrasound image from the ultrasound probe 22 is displayed in field 308 as the treatment head 20 is submerged in the binding medium. While the treatment head 20 is being driven, in step 422, the buoyancy of the treatment head 20 is detected and subtracted from the measured force applied to the treatment head 20 (e.g., by the robotic arm 14) to calculate the actual force applied to the treatment head 20. Unlike in Figure 9, the resistance indicator does not light up when the treatment head is pushed into the ultrasonic medium because the buoyancy due to the movement of the treatment head into the binding medium is subtracted from the measured force. In step 424, the buoyancy value is stored in the memory associated with the computing device. Method 400 is completed after buoyancy calibration by selecting the "Confirm" button 332.

[0159]

[0178] The buoyancy of the treatment head 20 is used to determine the force applied to the treatment head 20 as a result of contact with the patient through the film or membrane 48. Naturally, force can be applied to the patient by the treatment head 20 by driving the robotic arm 14. Buoyancy is the force that generally opposes the movement of the treatment head toward the patient and must be taken into consideration when calculating the force applied to the patient by the robotic arm. Naturally, the application of force to the patient may move or shift the patient's soft tissue, and in some cases may result in the movement of the treatment volume, lesion or tumor during treatment, leading to image fusion problems as described later. The ultrasound probe 22 may not necessarily contact the membrane 48 and may not apply force to the patient, but in some cases such contact and force application are necessary to ensure that the application of treatment from the treatment transducer 18 reaches the -z distal (from the treatment head 20) portion of the lesion or tumor. As described above, the resistance indicator 222, as shown in Figure 9, provides a visual signal of the resistance to movement the robot arm is subjected to, and in some cases, it can limit further movement of the transducer head or interrupt the application of treatment when a certain threshold is reached. In fact, the measurements and associated calibration values ​​and / or methods can be used to ensure that the system can take into account and deal with various force scenarios during the procedure, some of which may require pausing, ending, and / or resuming various steps of the procedure and / or treatment.

[0160] fusion

[0179] Figure 23 is a flowchart illustrating method 600 for forming a fused image by combining ultrasound images and preoperative or perioperative images for use in planning and performing patient treatment. Following the completion of method 400, after buoyancy is detected and actual force calibration is completed (see Figure 22), an ultrasound 3D volume of the region of interest in which the target to be treated is visualized can be captured. This captured 3D volume can then be fused with preoperative or perioperative images (e.g., MRI, CT, CBCT, X-ray images and / or other appropriate medical imaging) so that the location of the live (2D) ultrasound image can later be spatially determined relative to the preoperative or perioperative image volume. To initiate the fusion process, a user interface (UI) 500, as shown in Figure 24, is displayed on the display 24 of the histotripsy system 10. Note that the fusion skip button 503 can be selected at any point before or during the fusion process to completely skip the process described below and proceed to the planning stage described later without performing the fusion process.

[0161]

[0180] Following instructions on the UI 500, in step 602 the imaging probe 22 is extended from the treatment head 20 so that it extends beyond the treatment transducer 18, and the user can drive the robotic arm 14 and the treatment head 20 to locate the target area or region of interest, for example using a space mouse 36. During this process, a live ultrasound image 502 is acquired and displayed on panel 504 of the UI 500. A reference image selected during this session (see Figures 12 and 13) is displayed on panels 506 and 508, and the view displayed on panels 504, 506, or 508 can be adjusted using button 509. In step 604, the treatment head 20 is positioned to optimize the visualization of the target. In step 606, the treatment head 20 and imaging probe 22 are moved to center the ultrasound image (as displayed on the UI) the region of interest and, specifically, the lesion, if visible. In step 608, the imaging probe 22 is rotated using the orientation tab 40 to examine the region of interest in multiple planes (e.g., sagittal and axial) so that the region of interest, and specifically the lesion, is reliably located near the center of the ultrasound image in multiple planes.

[0162]

[0181] In step 610, the imaging probe is moved to the -Y position as indicated by the imaging probe position indicator 505. Once the imaging probe 22 is positioned in this manner, in step 612, the patient may be instructed to hold their breath to minimize patient movement caused by breathing, and in step 614, the ultrasonic sweep is initiated by the selection of button 507. The breath-holding may be continued for the duration of the ultrasonic sweep, and in some embodiments, the ultrasonic sweep time is shorter than the breath-holding time. During the ultrasonic sweep, as shown in Figure 25, the treatment head 20, driven by the robotic arm 14, is moved along the X axis by approximately 30 degrees in the -X direction and approximately 30 degrees in the +X direction from its starting position. In other embodiments, depending on the imaging probe, patient size and / or orientation, the ultrasonic sweep may be as small as 15 degrees in both the -X and +X directions, or as large as 45 degrees in both the -X and +Y directions. A progress indicator 512 on the UI 500 shows the progress of the sweep, and as described above, the movement of the treatment head 20 during the sweep is along the X axis. In step 616, an ultrasound image is captured at any or more points along the sweep. Multiple ultrasound images may also be associated with a particular point along the sweep, but the data is typically recorded / stored for only one sweep. The sweep may be configured to move in a specific direction (e.g., an arc or rotation of a predetermined distance or degree). In one configuration, the sweep first moves at a -X angle and then at a +X angle, which is typically from the patient's feet toward the patient's head, depending on the patient's orientation relative to the system specified in step 412. This direction may be modified in different embodiments. When the sweep is completed in step 618, the robotic arm 16 and treatment head 20 stop moving, ultrasound imaging stops, and breath-holding also stops. If the movement of the robotic arm 14 and treatment head 20 exceeds a threshold force during the sweep, the sweep automatically stops moving and moves in the opposite direction.For example, if the treatment head 20 comes into contact with another part of the system, such as a part of the coupling assembly 46, while moving at a -X angle, a threshold force is triggered, stopping the movement of the treatment head 20 and reorienting it in the opposite direction (+X angle). Similarly, during a sweep, the user can input a command to stop movement in the current direction using the sweep stop button 510. For example, if the user wants to stop the sweep movement before reaching a -X angle, the user can select the sweep stop button 510, which will stop movement in the -X direction and then start movement in the +X direction. The system can display real-time force monitoring feedback in the system UI, including force notifications by text, color-coded force states, graphics and overlays, and / or other mechanisms. Depending on the embodiment, the system UI may also notify / display to the user the location of the source (e.g., the angle of the transducer housing, the translational ultrasound imaging probe, etc.).

[0163]

[0182] In step 620, the image review panel 514 is displayed on the UI 500 (Figure 26). The image review window 514 allows the user to review all images from the sweep by playing the images as a video. The purpose of reviewing the sweep is to confirm that the region of interest (including anatomical landmarks and structures), and specifically the lesion or histotripsy target, has been fully captured in the sweep. As shown in Figure 26, the image review window 514 also allows trimming or clipping portions of the ultrasound sweep. This may be appropriate if the sweep contains images that did not include the region of interest, or if the user wishes to remove those images for various reasons. Trimming the ultrasound image recording is an optional step 622. In step 624, the image review window 514 also allows the sweep to be repeated by undoing the sweep or by selecting the "Back" button, which returns the method to step 602, allowing the user to repeat the sweep. Panel 504 displays the ultrasound images in a standard planar view of those images, while a second panel 516 displays the ultrasound images collated into a 3D volume from a side view perpendicular to the direction of the sweep. Collation into a 3D volume can be achieved by associating each captured image (or frame) with the robot position and timestamp to form the volume. As shown in Figure 26, the sweep contains 507 images captured during the sweep. By selecting one of the trimming buttons 518 and dragging it along the recording line 520, the ultrasound image associated with that point in the sweep is displayed in panel 504, as shown in Figure 26. In this way, the user can adjust the trimming button 518 to reduce the number of ultrasound images in the sweep. Moving the trimming button 518 along the recording line 520 provides a view of the portion of the sweep that the user wants to trim or remove from the sweep.The purpose of sweep trimming is to remove any ultrasound images that do not contain clear data, such as images taken over interfering biological structures like the intestines, lungs, or ribs, which may prevent the image-based fusion algorithm from optimally integrating the ultrasound image data with preoperative or perioperative images. Therefore, in some cases, the sweep may be taken over and / or between the ribs to enable fusion using transribular and / or rib medial approach. As can be seen in Figure 26, the movement of the trimming button 518 progresses to the 105th image out of 507 captured images. After the trimming button 518 has been used and unwanted ultrasound images (e.g., images 1-104) have been removed, the save recording button 522 can be selected in step 626 to save the selected ultrasound images. Of course, the trimming button 518 does not always need to be used, and the save recording button 522 may be selected without performing any trimming. Also, trimming may be performed or indicated using other on-screen indicators such as progress bars, ellipses, or other visual indicators or pop-up buttons, which are not shown.

[0164]

[0183] If the fusion step is not skipped, after the recording is saved in step 626, the Next button 523 is selected and the workflow proceeds to UI 500 shown in Figure 27. In Figure 27, the ultrasound images are registered to the preoperative reference images. Panel 504 shows the ultrasound image volumes in a standard orientation, and panel 525 shows those same ultrasound image volumes in a sagittal view. Panel 506 shows an axial view of the reference image volume or preoperative image volume, and panel 508 shows a sagittal view of the same preoperative image volume. A slider 524 allows the user to change the image within the volume displayed on each face. Although this specification describes the use of a slider on UI 500, those skilled in the art will see that the display 24 may be a touchscreen or trackpad 34, or other input devices may be used to perform scrolling or manipulation of the images (2D and 3D) as described herein. According to this disclosure, in step 628, the ultrasound image volume of panel 504 and the preoperative image volume of panel 506 are scrolled to identify landmarks or structures (intrinsic and / or extrinsic) that appear in both the ultrasound and preoperative images. These may include blood vessels, conduits, nerves, organ surfaces, organ / tissue structures, layers and / or components, and / or, in the case of extrinsic, various forms of reference markers or devices visible under multiple forms of imaging. The user can scan through various DICOM and ultrasound images on the touchscreen or trackpad to locate anatomical landmarks. Furthermore, the user can zoom in or zoom out of the image screen to assist in locating landmarks. When the user zooms in or zooms out of other views / images, one or more screens on the screen may automatically update / zoom in or zoom out. After such points are identified in each case, the “Registration Point A” button 526 can be selected, and the registration point 528 can be positioned in the appropriate location on the ultrasound image of panel 504 in step 630 and on the preoperative image panel 506 in step 632.The user may optionally scroll through the sagittal images of panels 508 and 525 to confirm the landmarks before or after placing the registration point 528 in the images of panels 504 and 506. If the placement of the registration point 528 is adjusted in either the sagittal plane view 525 or 508, the registration point 528 will be updated in the axial view shown in panels 504 and 506. If sufficient landmarks are not placed for registration in step 634, the method can return to step 628 by selecting the “Registration Point B” button 530, and another registration point 528 may be placed in the ultrasound image and preoperative image volume. This process of identifying landmarks and placing the registration point 528 can be repeated two, three, four, five, six, or more times. In some cases, if fine-tuning of the marker position is desired, basic arrows (not shown) pointing in four orthogonal directions from the registration point 528 may appear on one or more of the panels 504, 506, 508, and 525, thereby enabling fine-tuning of the registration point 528. In certain embodiments, it may be preferable to place the registration points on the same plane (e.g., axial, sagittal, and coronal). Depending on the embodiment, the UI may display the imaging plane along with overlays of the treatment head / treatment sound field force lines / volume and the transducer z-axis (aligned coaxially with the ultrasound imaging probe) to enable contextual viewing of the real-time patient setup, including various forms of 3D patient models and 4D models including motion modeling of organs, targets, and / or tumors in the context of treatment planning.

[0165]

[0184] Naturally, to improve the fixation and / or deformable registration of ultrasound and preoperative images, it may be desirable to place markers as close as possible to the tumor or lesion. This may include the center of the lesion or target, if visible in the ultrasound image or at the boundary of the lesion or tumor, but other locations away from the lesion may also be employed. In one embodiment, these locations are within approximately 5 cm of the lesion or tumor. This proximity helps compensate for the deformation of the patient's soft tissues caused by the placement of the connective assembly (and medium) on the patient's chest. The amount of connective medium is generally about 10-20 liters of fluid, and the weight of any part of this fluid can compress the soft tissues, thereby potentially shifting them from their position at the time of preoperative image capture. By finding markers near the lesion or tumor, and ultimately the target of treatment, the registration in this area is improved and the compressive effect on the connective medium is reduced. In some cases, perioperative imaging (MRI, CT, CBCT, etc.) can be taken with the patient's connective in place so that the deformation of the body caused by the connective itself can be taken into account. In other cases, baseline preoperative imaging of the patient can be obtained at an appropriate setup position for treatment. For example, if the treatment is performed in a positional manner, preoperative / perioperative images may be taken at this position.

[0166]

[0185] If sufficient landmarks or structures are identified in step 634, the fusion button 532 can be selected, and an application stored in the memory of the computing device on the cart 12 fuses the preoperative or perioperative images with the ultrasound images to display the axial view of panel 504 and the sagittal view of panel 506 in Figure 28.

[0167]

[0186] To perform image fusion, various different methods known in the art may be employed. One example of a fusion process may include a process that first includes a step of macroscopically orienting the ultrasound image volume and the preoperative or perioperative image volume based on the patient's orientation to the system, as set out in 412 above. Next, the fusion process may attempt to align marked registration points in both the ultrasound image and the preoperative or perioperative image so that they are spatially within 10 cm of each other. Next, a deformation model may be applied to the preoperative or perioperative image volume to account for compression due to the binding medium being placed on the patient. The ultrasound volume does not require a deformation model because the image acquired by the ultrasound sweep already reflects the deformation that the image receives from the binding medium. Finally, an image-based algorithm is employed to attempt to match the structure between the two image volumes. As a result, the ultrasound image from the ultrasound sweep and the preoperative or perioperative image are registered and finally fused, as shown in Figure 28. In other examples, an automatic registration algorithm may be used as the first fusion step, and the result may be further refined / updated by markers and / or structures as the second step.

[0168]

[0187] Slider 524 allows the user to scroll through the fused images in both panels 504 and 506 and view the fused images (step 638) in order to determine whether the fusion is close enough to allow for planning the treatment volume and treatment plan (described later).

[0169]

[0188] If adjustment may be necessary (affirmed in step 649), there are two options: firstly, the back button 534 can be selected, thereby returning the method to step 628 to move or position the new marker 528 as described above. After adjusting the registration point, selecting the merge button 532 (Figure 27) generates a new merge. Alternatively, if a smaller change is needed, the registration point adjustment button 535 may be selected in Figure 28, which returns to a screen equivalent to Figure 27, but if the merge button 532 is selected following the adjustment, the merge algorithm starts from the previous merge result and modifies it based on the updated registration point.

[0170]

[0189] If the registration point adjustment is insufficient to produce an acceptable fusion, advanced settings (affirmed in step 641) are available via the advanced settings button 536 (Figure 28). When the advanced settings button 536 is selected, the workflow proceeds to Figure 29 and step 642, providing two options for manual alignment of the reference image so that the reference image (preoperative or perioperative image) is aligned with the ultrasound image. By selecting the drag button 538, the preoperative or perioperative image of any selected plane can be dragged to improve alignment with the ultrasound image. Similarly, button 540 allows the user to rotate the reference image (i.e., preoperative or perioperative) to improve alignment of the fused image. To further assist this alignment, a blend mode field 542 is provided. The blend mode field 542 includes a slider 543 for adjusting the opacity of the reference image or preoperative image and a toggle 544 for turning the display of the ultrasound image and registration points 528 on and off. Naturally, turning the display of ultrasound images on and off allows for a more rigorous review of preoperative and / or perioperative images, and similarly, changing the opacity of preoperative images can help reduce features that obscure one image dataset when that image dataset is fused with the other. The toggle 544, which allows switching the display of registration points 528 off, allows images to be adjusted without necessarily considering the location of registration points on the image. Naturally, sliders 543 and toggle 544 can be used in various combinations when the user observes changes in UI 500 as they attempt to adjust the alignment of ultrasound and preoperative images. Image mixing, rotation, and dragging can be repeatedly adjusted and evaluated, including remarking registration points, until the user obtains an acceptable fusion.

[0171]

[0190] Figure 30 shows an additional aspect of the mixed mode field 542, which becomes available when the display of the registration points 528 is switched on, and the registration point deviation limit 545. This user-selectable limit allows a certain level of deviation in the location of the marked registration points in the two fused image datasets. The smaller the deviation, the closer the registration points 528 need to appear in the final fused images; the larger the deviation, the further away the registration points 528 may appear, yet still providing an acceptable fusion of the images. The deviation limit is most useful when the user is very confident or not very confident in the placement of the registration points. In one aspect, a moderate (10 mm) deviation limit is set by default. If the clinician is very confident in the fusion, they may try to improve the fusion by tightening the deviation limit. If the clinician is not confident in the fusion and is not confident that the same landmarks / anatomical sites are actually marked in both image sets, they may try to improve the fusion by loosening the deviation limit.

[0172]

[0191] Once all desired manual alignments are complete and the desired deviations are set, the fusion button 532 can be selected, and the application will again fuse the preoperative or perioperative images with the ultrasound images, taking into account the adjustments made, and then return to step 638 for review of the fusion, where the axial view of panel 504 and the sagittal view of panel 506 are displayed as shown in Figure 28.

[0173]

[0192] If fusion is acceptable (negative in steps 640 and 641), live fusion can be performed by selecting the Next button 537 (Figure 28). In step 646, the preoperative or perioperative image is fused with the live ultrasound image from the ultrasound probe 22 and displayed in panels 504 and 506 in step 646, as shown in Figure 31.

[0174]

[0193] The images shown in Figures 28-30 are static fused images, i.e., static fusions of ultrasound images from a sweep and preoperative images. Since these images are captured using the robotic arm 14, the positions of the treatment head 20 and, specifically, the ultrasound probe 22 from which each image was captured are known and stored in the memory of the computing device. By registering these static images and adjusting the registration point 528, the histotripsy system 10 can later fuse live-streaming ultrasound images at the captured positions with the preoperative images, as shown in Figure 31.

[0175]

[0194] As shown in Figure 31, once live fusion is available, the user can verify that the biological structure is aligned throughout the region of interest (e.g., a lesion or tumor or area of ​​unwanted tissue). This can be done in step 648 by using the space mouse 36 to move / position the robotic arm 14, along with the treatment head 20 and imaging probe, over the region of interest and observing the fusion through this region. Any movement of the treatment head 20 and, together with it, the treatment transducer 18 and imaging probe 22, whether robotically controlled or manual, is accurately represented in conjunction with changes in the view in the preoperative image. As part of this verification, in step 650, the imaging probe 22 can be rotated to confirm anatomical alignment in multiple planes. Referring to panel 506 as shown in Figure 31, the contour 546 of the original ultrasound sweep image volume is projected into the sagittal view. This allows the user to observe whether the imaging plane displayed on panel 504 is within the range of the input data used to generate the fusion into the preoperative image. The fusion is expected to remain most accurate as long as the live ultrasound image remains within the range of the input data. The live fused image can be moved, rotated, and zoomed in or out or panned in or out to verify the alignment of the biological structure. In step 652, if the biological structure is aligned to the region of interest around the tumor or lesion, the confirm button 548 can be selected, the fusion process ends, and the image displayed in UI 500 or subsequent UIs in the workflow (described later) will represent the live fused image. As can be seen in Figure 31, the registration point 528 may no longer be visible in the live fused image. If the fusion is not acceptable to the user, the back button 534 can be selected to return the method to step 638 for further fine-tuning, or the sweep repeat button 550 can be selected to return the method to step 602 to restart the fusion process.

[0176]

[0195] For several reasons, fusion may be unacceptable. Firstly, ultrasound sweep images are acquired during breath-holding when the lung is fully inflated, which may cause some movement of biostructure within the patient. In contrast, live ultrasound images are acquired during normal periodic breathing. Secondly, the registration point may not have been correctly identified in the separate image data, or it may have been selected too far away from the tumor or lesion. Also, a large deviation limit may have been selected, resulting in potential image inconsistencies. Any or all of these, along with other evidence, can cause unacceptable fusion requiring further adjustment or re-sweeping of the ultrasound probe 22.

[0177]

[0196] Figure 32 shows a further mechanism having a dropdown 552, which is a list of fusion results available for review in step 638. The dropdown 552 allows the clinician to troubleshoot the fusion results by comparing them with different inputs (e.g., adjusting the registration points), or gives the clinician the option to select earlier results to proceed to a live fusion review. In this way, the clinician can perform multiple attempts to perfect the registration and compare the results until an acceptable fusion is obtained.

[0178]

[0197] In other embodiments, DICOM data, including preoperative imaging, may also be modified in various ways, including pre-planning with various classifications (organs, structures, undesirable tissue volumes, etc.), simulated contours and their placement, and / or visualization mechanisms that may be used to indicate targeting and localization, and treatment plans in subsequent workflow steps. In some examples, the treatment plan may be displayed on top of the pre-planning, which may include a representation of contours (described in more detail below) that may have different characteristics from the pre-planning (represented, for example, with different line types, thicknesses, and colors than the "contours").

[0179] plan

[0198] Following the completion of the setup method 400, the workflow described herein, and optionally the fusion process of method 600, the workflow proceeds to the planning phase. In this phase, a clinician can plan one or more histotripsy treatments for a given patient. The workflow also allows the clinician to recall and view previous treatments and / or treatment plans so that additional overlapping or non-overlapping treatments may be planned. The UI 700 switches the indicator 702 from highlighting the “Localize” tab to highlighting the “Plan” tab, and after planning is complete, the “Treatment” tab will be highlighted. These tabs allow the user to understand where they are in the workflow at any point during the procedure. The planning phase is described in relation to the methods shown in the flowcharts of Figures 33A and 33B and the UI 700 shown in Figures 34–40. Figure 34 shows the UI 700 for presentation on display 24 used for planning histotripsy treatments. Unlike most procedures, this planning is performed in situ for the patient at the appropriate location on the patient's surface (e.g., the intervention treatment or operating table), and therefore there is no obvious need to reconcile preoperative images with live ultrasound images (e.g., the procedure may be purely ultrasound-guided). However, as mentioned above, fusion of preoperative or perioperative CT, MRI, PET and / or other image datasets enables the visualization of these images in relation to real-time live ultrasound images.

[0180]

[0199] The UI700 includes several buttons 704 that enable different aspects of the subsequent planning process. These buttons 704 include a “Contour Diameter” button, a “Margin Size” button, and a “Focus” button. In certain embodiments, these buttons 704 may be labeled “Contour Diameter,” “Margin Diameter,” and “Focus Steering.” It should be understood that the contour diameter refers to the contour diameter of the lesion or tumor of interest, which may be up to 3 cm, depending on the embodiment. The margin size or margin diameter provides an additional 0.5 cm around each side of the contour, which can total about 1 cm for a diameter contour. In certain embodiments, various combinations of contour diameter and margin size / diameter may total 4 cm. Selecting one of these buttons allows for planning or adjusting various parameters of the procedure, as described below. It should be further noted that various UI features, including but not limited to contours, margins, focus, and / or indicators / force lines, may be selectively displayed on or removed from the UI at specific points in the user workflow, thereby enabling better visualization of the lesion of interest during planning or treatment.

[0181]

[0200] In Figure 34 and UI700, the live ultrasound image 706 is displayed fused on the corresponding slice 708 of the perioperative or preoperative image (e.g., CT, MRI, or other image) in field 710, based on the fusion method 600 described above. In field 710, the image shows the ultrasound view corresponding to the axial view of the patient in this example. The associated sagittal view of the ultrasound image 706 fused with the perioperative or preoperative image is displayed in field 712. In field 712, an indicator 714 is displayed, which is the contour of the ultrasound sweep used to generate the fusion, intended to indicate whether the image view overlaps with the original fusion data, thereby indicating a more reliable fusion. Field 716 shows a 3D model 718 formed from the preoperative or perioperative image (e.g., CT or MRI image dataset) fused with the live ultrasound image 720. The 3D model 718 is registered with the ultrasound image 720 and displayed as a fused 3D model with the live ultrasound image 720. The live ultrasound image 720 is displayed in the anatomically correct location of the 3D model 718. As the treatment head 20 and specifically the ultrasound probe 22 are moved over the patient, the ultrasound image 720 and its position in the 3D model are updated accordingly. The 3D model 718 also shows the acoustic path volume 722, which is the volume through which the therapeutic ultrasound emitted from the therapeutic transducer 18 passes before reaching the focus where treatment is performed. In fields 710 and 712, a two-dimensional representation of the acoustic path volume 722 is displayed as lines of force 724 ending at the focus 726, indicated by a cross or otherwise shown. The lines of force allow the user to understand / visualize potential obstructions and, furthermore, to minimize (or avoid, if possible) those obstructions. However, it should be understood that in many cases, the target tissue volume may not be completely free of obstructions. By default, the focus 726 is positioned at the farther point in the -Z direction (the deepest part of the patient's body or the part furthest from the surface of the patient's skin) relative to the target 728 and margin 732 contour.The positioning of the crosshair 726 at this location, and the subsequent steps described below, allow the user to confirm that there are no potential obstructions at the deepest point of treatment and / or that the deepest point of treatment required will receive histotripsy treatment. Naturally, if there is no fusion, no fused image is displayed in field 710, and all planning steps as described herein are performed on live ultrasound images, with preoperative or perioperative images optionally displayed in field 712 to assist the user if they were imported during patient registration.

[0182]

[0201] Once the localized portion of the workflow (for example, method 400, which optionally follows method 600 and therefore may or may not involve fusion) is complete, the UI 700 is displayed, and the initial target contour 728 is automatically displayed. The target contour 728 is an initial representation of the shape of the tumor or lesion to be treated. In one embodiment, the default target contour 728 has initial dimensions of 20 mm along each of the X, Y, and Z axes, as indicated by the indicator 730. As will be described later, the values ​​indicated by the indicator 730 can be adjusted by the knob 28, so that the target contour 728 can be adjusted to more closely match the actual shape and size of the tumor or lesion to be treated. Furthermore, if determined by the user, the location of the target contour 728 can be moved to a more appropriate location by using the space mouse 36 and the X, Y, and Z knob 28 functions. A margin indicator 732 is also displayed around the target contour 728, showing the volume of tissue around the target contour 728 that will also be treated, in order to ensure that the lesion or tumor is completely treated. As detailed below, the size of the margin indicator 732 defines the boundary of the target contour 728, which is a set value (e.g., 2 mm, 4 mm, 6 mm) that can be adjusted by the user or system to increase or decrease the margin around the tumor or lesion being treated.

[0183]

[0202] Method 800 begins in step 802, where the treatment head 20 is positioned so that the imaging probe 22 is placed over a rough area of ​​a mark optionally placed over the patient in relation to step 408 of Method 400, using a free-drive button 44 or a space mouse 36 operably connected to a robotic arm 14. As described above, the ultrasound probe 22 captures an ultrasound image for display within the field 710, and the treatment head 20 is moved so that the tumor or lesion to be treated is observable in the live ultrasound image 706. In addition to or instead of this, the tumor or lesion to be treated may be identified using surrounding / proximity anatomical landmarks. For example, this may be particularly useful when direct visualization is at least partially obscured or limited. This may require moving the treatment head 20 around the mark to ensure that there are substantially no obstructions or interferences (e.g., ribs, cartilage, intestines, GI gas, etc.) in the acoustic path volume 722 and lines of force 724 that could affect the energy requirements for bringing the lesion or tumor to treatment.

[0184]

[0203] The UI700 is configured to allow the user to create and view a planned treatment volume. As described above, the planned treatment volume includes a target contour 728 around the tumor or lesion and a margin contour 723 around the target contour 728. Both the margin contour 732 and the target contour 728 are configurable by the user. Also, the default configuration, as shown in Figure 34, may change in size and shape based on the application of the intended use or organ region (e.g., liver, kidney, thyroid, breast, etc.). In addition, both the target contour 728 and the margin contour 732 may have limitations imposed by the system (e.g., minimum or maximum size or eccentricity).

[0185]

[0204] The planned treatment volume can be displayed to the user via UI700 in various ways, including, but not limited to, 2D views of fields 710 and 712 or 3D models of field 716, using real-time or live-streaming imaging data, or pre-acquired preoperative images (CT, MRI, etc.), or perioperative imaging acquired during the procedure fused with real-time imaging data (cone-beam CT, intraoperative CT, etc.). The planned treatment volume can be displayed as graphical features or computer-generated overlays or models, which can further display important planning features or therapeutic transducer-related features, similar to sound field force lines, including geometric focus or focus 726, or a default treatment focus based on predicted aberration / attenuation, and such features may dynamically change position or location based on robot movement or the position of imaging probe 22. Further details of generating the treatment volume and displaying the treatment volume on UI700 are outlined below with Method 800.

[0186]

[0205] Upon entering UI700 (for example, following the acceptance of fusion in step 652), the application automatically selects to illuminate the contour diameter button 704, which is related to the target contour 728 on which the initial planning is performed. The user can optionally select the margin size or focus steering button, which will be described in more detail below. Thus, in step 804, the user confirms that the contour diameter button is highlighted. In step 806, the treatment head 20, with the imaging probe 22 observing the XZ plane (for example, the axial plane of the patient), is moved by driving the robotic arm 14 using the space mouse 36 or a free-drive mechanism until the target contour 728 is centered in the target tumor or lesion in the YZ plane. Note that while the treatment head is moving, the resistance to movement experienced by the robotic arm 14 is constantly observed and displayed, and if the resistance exceeds a predefined threshold, the movement is slowed down, as will be described later. When the target contour 728 is located approximately in the center of the tumor or lesion, the Y and Z dimensions of the default target contour 728 are adjusted using the knobs 28 to change the dimensions of the target contour 728 in the Y and Z dimensions, respectively, and this adjustment is graphically displayed in the indicator 730.

[0187]

[0206] In addition to ensuring that the target contour 728 is centered on the tumor or lesion, sound field force lines 724 are displayed on the UI 700 while the robotic arm 14 and imaging probe 22 are moved. During this movement, the user can use the force lines 724 as a guide to facilitate minimizing intersections with interfering structures (e.g., bone or other tissues) that could negatively impact the performance of the treatment by increasing the energy required to achieve the treatment. Alternatively, the force lines 724 can be used to identify the histotripsy treatment window by knowing if there are any interfering structures. To reduce intersections with interfering structures, the treatment arm menu 733 can be opened, and the type of movement of the robotic arm 14 can be limited to rotation only. Next, the position of the treatment head 20 is rotated using the space mouse 36 while the target contour position 728 is maintained over the tumor or lesion. The target contour position 728 can also be maintained over / in close to anatomical landmarks according to user instructions if direct visualization may be unclear. The confirmation in step 808 that there are no obstacles in the acoustic path may be performed simultaneously with step 806. Alternatively, it may be confirmed here, preferably, that the acoustic path contains obstacles. Specifically, at least the 3D volumetric view shown in field 716 can provide the user with acoustic path information.

[0188]

[0207] In step 810, the imaging probe 22 is rotated 90 degrees as shown with reference to the position indicator 219 in Figure 35 to view the XY imaging plane (e.g., the patient's sagittal plane), and the treatment head 20 and specifically the imaging probe 22 are moved until the target contour 728 is centered on the target tumor or lesion in the XZ plane. In other words, the target contour 728 is evaluated in multiple planes. Those skilled in the art will see that this centering takes into account the movement of the tumor or lesion due to the patient's respiratory cycle, which is generally visible in the sagittal plane. The tumor or lesion is intended to remain within the contour through the movement of the respiratory cycle. To change the dimensions of the target contour 728 in the X and Z dimensions, the X and Z dimensions of the target contour 728 are adjusted using the knobs 28. Again, in step 812, it is confirmed that there are no obstructions to the force lines 724 or that the force lines indicate a preferred treatment window, which may be done concurrently with step 810.

[0189]

[0208] Following steps 810 and 812, in step 813 the imaging probe is rotated 90 degrees back to view the YZ imaging plane (e.g., the axial plane of the patient) to ensure that the target contour 728 remains centered on the target tumor or lesion and that the sound field contains minimal interference structures. If necessary, this process is repeated from steps 806 to 812 until the contour is centered on the tumor or lesion and the sound field is optimized in both or more imaging planes.

[0190]

[0209] Next, in step 814, one of the knobs 28 can be used to adjust the margin size as shown on indicator 730. As shown in Figure 36, the margin is set to 3.4 mm, but this value can be increased or decreased as needed to ensure that a sufficient amount of margin is defined. However, the margin that defines the overall healthy tissue that will be sacrificed to ensure complete treatment is usually made as small as possible, where appropriate, so that as much healthy tissue as possible is spared from treatment.

[0191]

[0210] In step 816, following the selection of the focus button 704 in Figure 37, the focus 726, shown as a crosshair, can be adjusted by moving the crosshair 734 up and down on the focus axis 735 using one of the knobs 28, as indicated by the indicator 730 shown in Figure 37. In step 816, the focus steering is adjusted using one of the knobs 28, as indicated by the indicator 730, to reach the desired depth. As shown in Figure 34, the default focus 726 is positioned at the point furthest in the -Z direction relative to the target contour 728 and margin contour 732 (the deepest point in the patient's body or the point furthest from the patient's skin). Adjustment of the focus 726 may be necessary if the planned treatment volume cannot encompass the distal edge of the target tumor. The planned treatment volume may not be able to encompass the distal edge of the target tumor if moving the treatment head any further would hit the patient's abdomen. Following the focus adjustment, the steps of adjusting the location and size of the target contour 728 and margin contour 732 can be repeated. Depending on the embodiment, the user may choose to change the treatment head to obtain different focal depths. A treatment head with more transducer elements may allow treatment to penetrate deeper into the patient. In another embodiment, if the target lesion or tumor is located in a shallow or shallow part of the body, the user may choose to downsize to a treatment head with fewer transducer elements to reduce the energy applied to the tissue.

[0192]

[0211] After the user is confident that the target contour 728 and margin contour 732 substantially follow the tumor or lesion throughout the entire tumor or lesion, and that the force lines 724 define a substantially unobstructed volume throughout the tumor or lesion (or that a favorable acoustic window with an obstruction is obtained), the user can select the Next button 738 to begin the plan verification step in step 818, or the UI 700 as shown in Figure 38 will be displayed. When the workflow proceeds to plan verification, the application saves the location of the target contour 728 and target margin 732 (i.e., the planned treatment volume) in memory, which may be referred to as "locking" the plan to the target tumor or lesion location. Once the plan is locked, the robotic arm is moved so that the movement of the robotic arm 14 with the treatment head 20 is detached from the location of the plan, so that the contour displayed on the ultrasound image becomes a cross-section of the planned treatment volume calculated by the application based on the robotic arm's current location relative to the location of the saved location of the planned treatment volume. Naturally, the robotic arm 14, driven by the mouse 36, adjusts the position of the ultrasound probe 22 so that the user can observe the entire tumor or lesion and ensure that the entire tumor or lesion is within the target contour 728. This movement of the imaging probe 22 also makes it easier to confirm that the tumor or lesion is within the target contour 728 during the respiratory cycle. If, at any point while moving the imaging probe 22, the tumor or lesion is outside the target contour, the contour can be adjusted using the knob 28.

[0193]

[0212] In some cases, the user may be able to "lock" the contour and treatment plan in the 3D space displayed on the UI, and further, the plan may be robotically controlled to examine adjacent anatomical spaces / locations and / or organs and structures. This step can be used to help evaluate the planning location for procedures using fusion where ultrasound visualization of the tumor itself is difficult, but tissue imaging is sufficient. In this example, the user can use anatomical landmarks or structures in DICOM data (e.g., MRI or CT or CBCT) to verify the tumor and the planning location. In other examples, the user may simply use this mechanism to evaluate the planning parameters and placement in streaming ultrasound. In some cases, where sensitive organs (pancreas) and / or structures (intestines) may be close to the plan, this may allow the user to evaluate the treatment site in more detail and from a larger perspective. Depending on the configuration, with the plan locked, the system may include a mechanism (and graphics and UI inputs) to return to the planning or examination point to allow the system to automatically return and position the plan to a central point (and / or other planning location) at the user's discretion / desire.

[0194]

[0213] After the system has included a locked plan, that locked plan can be stored or linked to a specific treatment protocol (and tumor) or a specific patient. If additional treatment is needed or preferred, the locked plan can be made accessible in the future, thereby allowing the histotripsy system 10 to recall the locked treatment plan after the patient has been positioned for treatment, thereby allowing the robotic arm to be automatically driven in 3D space and the treatment transducer to be positioned and aligned to a center point (or another identified point) within the locked plan. Aligning to a locked plan can omit patient setup steps, including localization steps and specific steps in the planning steps. In some cases, the UI may also be configured to show markings of previous user-selected plan locations, including locations where the user has evaluated possible placements of the treatment plan, including a display of possible crosshair locations (e.g., as the plan center point) for representative possible treatment plans. In one example, the system software may allow the user to evaluate multiple planning locations, in which case the user can mark those locations, the system software may remember the robot's position and orientation, and the user may return to a previous planning location as desired. In another example, this functionality may be configured to allow the evaluation and positioning of multiple treatment plans in relation to each other in 3D space, including allowing the user to superimpose and / or separate treatment plans according to user definitions.

[0195]

[0214] Figure 38 shows a typical diagram of the target contour 740 in the UI 700 adjacent to button 703, which may be called a “plan point or survey point” 739. This allows selection of the center point of the plan and endpoints along the X, Y, and Z axes (e.g., -X, +X, -Y, +Y, -Z, +Z). In one embodiment, this function can be configured to allow the user to instruct the robot to automatically survey various points of the plan, including, for example, the plan endpoints and / or center point, based on the user-selected plan or survey point. In one example, in step 820, the user can select one of the survey points 739 of the target contour graphic 740 in step 820. The actual survey point locations associated with the target contour graphic 740 are defined by the target contour 728 generated in steps 806-812. In one aspect of this disclosure, at least a -Z investigation point 739 must be selected, and in step 822, the move to the point button 742 is pressed during the movement of the treatment head 20, so that the focus 726 of the therapeutic transducer 18 arrives at the -Z position of the target contour 728 set in the previous step. The -Z position is the highest point of the target contour 728 (e.g., vertically from a patient lying horizontally) that will be treated by the therapeutic transducer 18 in subsequent embodiments of the workflow. Verification that the ultrasonic medium is sufficient (i.e., the therapeutic transducer 18 remains submerged and free of bubbles), as described in field 744 on the UI, ensures that good ultrasonic coupling between the therapeutic transducer 18 and the patient is always obtained in subsequent treatment stages. Visual inspection of the therapeutic transducer 18 may be used to confirm that the therapeutic transducer is free of bubbles and remains submerged. In some embodiments, a color indicator on the UI may also provide information regarding the spatial location of the treatment head. In step 824, while moving the therapeutic transducer 18 to the investigation point 739 of the target contour graphic 740, the resistance to movement experienced by the robotic arm is constantly observed.If the resistance to movement is greater than a threshold, in step 826 an indicator may be displayed on the UI 700 (e.g., a yellow, orange, or red color border, see Figure 9), and the movement of the therapeutic transducer 18 and the therapeutic head 20 is slowed down. The resistance is continuously monitored to determine in step 828 whether the resistance exceeds a second threshold. If the resistance exceeds the second threshold, in step 830 the movement of the robotic arm 14 and the therapeutic head 20 may be slowed down, paused, and / or stopped, and in step 832 mitigation measures may be displayed. Furthermore, the UI may display sources and / or interactions that produce force feedback (e.g., locations on the therapeutic head interacting with the patient and / or the coupling frame). Naturally, more thresholds may be adopted without departing from the scope of this disclosure. For example, a first threshold may cause a speed reduction of up to 50% of the normal drive speed, a second threshold a speed reduction of up to 25% of the normal drive speed, and a third threshold may cause the robotic arm 14 to stop driving. However, if in step 828 the resistance remains below the second threshold and the user has not finished moving the treatment head 20, the method proceeds to step 834, where it is determined whether the survey point 739 has been reached. If not, the method returns to step 826 to continue the slowed movement, but if the survey point 739 has been reached, the method proceeds to step 836, where it can also be reached if the resistance to movement in step 822 never exceeds the first threshold. In step 836, a query is made as to whether it is necessary to drive to an additional survey point 739. If affirmative, the method returns to step 820, but if sufficient or all survey points have been driven, the user can select the next button 746.

[0196]

[0215] At any point during plan validation (for example, after the display of mitigation measures), the user may select one of the buttons 704 and adjust the target contour 728, margin contour 732, or focus 726 (as described above for these mechanisms) in step 833, and then resume plan validation as described above without navigating away from the UI 700 shown in Figure 38. The user may feel the need to adjust the plan, for example, based on the observation that part of the tumor or lesion is not within the treatment volume, or because the resistance to movement the treatment head 20 receives is too great for the procedure. As disclosed previously, these steps may include using / returning to a previously saved position / orientation to evaluate alternative techniques.

[0197]

[0216] Furthermore, as shown in Figure 38, the planning location button 736 becomes available at this time. When the planning location button 736 is selected, the knobs 28 can be used to adjust the planning location in the X, Y, and Z axes, and the contour position on the ultrasound image is immediately updated accordingly in the form of one or more image overlays. This is an alternative to using the back button to return to step 804 and begin adjusting the planning location. If the user wants to change the angle or position of the treatment head to further optimize the sound field, the user must select the back button and return to step 804. In some embodiments, the system software may allow the user to lock onto a target location and examine the area around the selected point to evaluate the optimal or preferred acoustic window to the user-selected target. In some examples, this may allow the user to evaluate trade-off decisions when the approach route may include intestinal and rib obstructions and select a preferred approach route around and / or through these structures. In some representative examples, the user may use this mechanism to treat while avoiding the intestines but passing through one or more ribs. In another example, this mechanism may also be used to assess potential physical collisions with the patient and / or the coupling setup, in addition to evaluating the acoustic pathway.

[0198]

[0217] Naturally, the movement of the treatment head 20 so that the focus 726 is at the +Z survey point 739 is most likely to encounter the most resistance, and therefore, according to one aspect of this disclosure, it is driven to at least the +Z and +Z survey points using steps 820-836. In another aspect, during the treatment phase, all of the survey points 739 are driven to ensure that resistance exceeding a second threshold is never encountered. Also, as described elsewhere in this specification, other protocols may be employed to limit movement in the event of a violation of one or more thresholds.

[0199]

[0218] Following the selection of the Next button 746, the UI 700 displays the image in Figure 39. As shown in Figure 39, in step 838, the user is asked to place marker 748 at the intersection of the body and another location in the ultrasound image 706 displayed in field 710, in this case the intersection of the muscle layer and subcutaneous fat layer of the patient and / or planned location. Following the placement of marker 748, the user may select the Next button 750, and the UI 700 displays the image in Figure 40. In step 840, in order to ensure that the lesion is reliably positioned in relation to the contour according to user preferences and treatment intentions, the imaging probe 22 is rotated to display live ultrasound having the target contour 728, margin 732 and lines of force and the location of the observed tumor or lesion relative to these plans and planes (e.g., axial and sagittal directions), thereby confirming that the target contour 728 margin 732 is aligned with the tumor or lesion in multiple planes throughout the entire respiratory cycle. In one example, this involves ensuring that the tumor and / or target tissue are completely enclosed within the contour to ensure complete tumor / tissue destruction. In a different example, the user may desire a treatment plan that partially treats the tumor / target tissue, including potentially and intentionally leaving the remaining tumor and / or non-tumor tissue adjacent to the treatment. The workflow may continue to include driving the treatment head 20 to the -Z point in the plan to reconfirm that the binding medium level in the binding assembly 46 is sufficient so that the treatment head remains sufficiently submerged in the binding medium at the -Z position. After the treatment head 20 has reached the -Z point, the confirm button 754 becomes available. Optionally, the treatment head 20 may again be driven to any other investigation point or planning point 739 by selecting an investigation point 739 and moving to the target button 742. For example, this can serve to ensure that no issues of force or resistance are encountered with respect to physical collision or interaction with the patient or binding assembly (e.g., verifying that the focus 726 can be operated to the +Z position). The step of placing markers at the intersection of the patient's muscle layer and subcutaneous fat layer may be repeated, for example, when the treatment head 20 changes position.

[0200]

[0219] If, as observed on real-time ultrasound and / or using other imaging data, it is found that the target contour 728 or margin 732 is not aligned with the tumor or lesion at any point throughout the respiratory cycle, the plan adjustment button 752 may be selected, and the method returns to step 804, where the target contour 728 is redefined. However, if the plan has been validated in steps 840 and 842, the confirm plan button 754 can be selected to proceed to treatment.

[0201] Resistance detection

[0220] At various points in the localization, planning, or treatment phases of the procedure, the robotic arm 14 and the treatment head 20 may encounter feedback of resistance and / or increased force to their movement. Due to the aforementioned resistance, force, and possible collisions, the system may be configured to store / record the posture and position of the robotic arm, as well as the treatment plan and / or target location, so that the user can locate and / or return to each posture, position and location if the system encounters resistance and / or force that requires the treatment head to be positioned away from the patient. Also, part of this resistance to movement, at least roughly in the Z direction, is the buoyancy of the treatment head 20, and this buoyancy may be taken into account and / or continuously calculated and subtracted from the resistance measurement, as described in Method 400. During the movement and movement of the robotic arm 14 and the treatment head 20, the histotripsy system 10 monitors the resistance (force acting on the treatment head in the opposite direction of movement) resulting from the physical interaction between the treatment head and the coupling assembly 46 or the patient. Understanding the interaction of resistance and force as the treatment head 20 is moved to each examination point or otherwise moved around the patient ensures that the therapeutic transducer 18 can deliver histotripsy to all parts of the target contour 728 and margin 732 without causing injury or harm to the equipment or the patient. Also, as described elsewhere, pressure applied to the patient through the treatment head 20 may, in some cases, move, shift, or strain / deform the patient's soft tissues. This strain and / or deformation may be problematic when using the fusion application (described above) or the 3D fusion model 718, and may result in a discrepancy between the image and the body.Therefore, in order to ensure that the target contour 728 and margin 732 accurately reflect the tumor or lesion to be treated, and that no distortion occurs in the area of ​​the patient being treated, which could result in incomplete treatment or application of treatment to tissue outside the target contour 728 or margin 732, the force or pressure applied to the patient by the treatment head 20 must be kept below a defined threshold when creating the 3D fusion model and in subsequent treatment planning. Depending on the system embodiment, the fusion model may include various additional sensor inputs to enable tracking of movement, distortion, and / or deformation, and further enable a dynamically deformable registration model that is updated to take such issues into account.

[0202]

[0221] According to this disclosure, an indicator of the magnitude of pressure or force being applied to (or resisting) the patient or resistance to the movement of the treatment head 20 may be displayed on the UI as a resistance indicator 222 (see, for example, UI 200 in Figures 9 and 10). As shown, UI 200 is surrounded by a border or resistance indicator 222 of a different color. As the robotic arm 14 and the treatment head 20 are moved above and / or around the patient, the color of this resistance indicator may change, for example, yellow for low resistance, orange for medium resistance, and red for resistance exceeding a threshold. Thus, the resistance indicator is an indicator of the magnitude of the force that the robotic arm 14 must apply to drive the treatment head 20 to a location over the patient in order to overcome the resistance to the movement of the treatment head provided by the patient's body. Depending on the aspect of this disclosure, based on a predefined threshold or limit, the histotripsy system 10 may enable or disable certain aspects of both the robotic arm's treatment head positioning interface control (e.g., the free drive button 44) and / or the system user interface console, including but not limited to the space mouse 36. Furthermore, the histotripsy system 10 may have specially designed responses and actions when a resistance or force threshold / limit is reached. These may include / have similar or different behaviors based on the force source (e.g., a telescopic treatment head imaging probe or a coupling collision). While the above relating to Method 800 describes only two such responses, specifically slowing down or stopping the drive of the robot arm 14 and treatment head 20, these responses may include, but are not limited to, slowing down, pausing, or reversing the movement of the robot arm 14 and treatment head 20, or may be configured not to alter any histotripsy system-instructed automatic movement or movement of the robot arm (e.g., automatic movement to a planning point).

[0203]

[0222] In one example, the system is configured such that when the detected resistance is low, the automatic movement of the robotic arm 14 and treatment head 20 is not restricted, and user-instructed movement using the free-drive button 44 or space mouse 36 may have its speed reduced in the direction of the resistance. When a moderate resistance is detected, the manual movement speed is further reduced in the direction of the resistance, and automatic movement is not slowed down in this case either. When the resistance limit is reached, manual movement in the direction of the resistance is prevented, and automatic movement can continue as long as a threshold (e.g., a resistance of 50 Newtons) is not reached, at which point a soft emergency stop is initiated and an appropriate corrective action message is displayed on the UI. These restrictions on movement are applied throughout the entire procedure and take into account the pressure exerted on the treatment head 20 due to the patient's respiration and the buoyancy of the treatment head 20. In this way, with buoyancy taken into account and substantially canceled out, the true value of the force exerted on the treatment head 20 or the resistance caused by the patient's biostructure can be evaluated and dealt with accordingly.

[0204] treatment

[0223] Entering the treatment phase of the workflow, the system may be configured with several mechanisms and steps to enable bubble cloud detection, visualization, calibration (locating the bubble cloud in 2D or 3D space of the imaging to account for any focus shift), aberration correction, and threshold determination and setting. These mechanisms and steps may be implemented in various ways to best enable ease of use and user experience. Depending on the example and configuration, the system may guide the user through various steps to initiate treatment in order to determine one or more of the listed mechanisms (e.g., locating the cloud for calibration). In other configurations, the system may automate the steps and require the user to verify / approve the steps (values ​​set by the system). Furthermore, various UI graphics or overlays may be used to display these mechanisms and associated user guide text to support the various steps.

[0205]

[0224] In one system configuration, after the target contour 728 and margin 732 are set and it is verified that the coupling medium is sufficient and the treatment head 20 can be driven to each of the investigation points 739 without exceeding the threshold resistance or force value, the patient can receive treatment, following the selection of the confirmation button 754 in the UI 700 in Figure 40. Figure 42A shows the UI 1100 employed to treat a patient using an ultrasound image 1102 which is displayed and overlaid with the treatment contour 728 and margin 732, force lines 724 and focus 726. The UI 1100 shows that the indicator 702 is lit as the "treatment" indicator. In order to carry out treatment method 1000, before proceeding with the application of continuous treatment via the treatment transducer 18, the location of the patient's (in vivo) bubble cloud must be calibrated and the voltage setting value for driving the treatment transducer 18 must be set.

[0206]

[0225] Method 1000 begins with an in vivo calibration process intended to align the focus indicator 726 to the location of the treatment focus where the bubble cloud will occur. It should be noted that this in vivo calibration step is required in addition to the calibration described in Method 100 due to intrinsic variations in intervening tissue between the treatment head 20 and the tumor, which may slightly deflect the focus in various ways. The calibration in Method 1000 ensures that the bubble cloud initially occurs near the focus 726, but the final offset must be determined uniquely for each patient or tumor location by calibrating the cloud location to the center of the planned treatment volume. To begin, the system automatically moves the treatment head 20 in step 1002 so that the focus 726 is at the center of the planned treatment volume, as shown in Figure 42A. Instructions are given to activate the voltage knob 32 in step 1003 by selecting button 1103 and then pressing the voltage knob 32, as shown in Figure 42A. Next, the treatment output is increased until the bubble cloud 1104 (Figure 42B) is visualized and / or an audible signal is heard by rotating the voltage knob 32. If the bubble cloud is visualized to be offset from the focus 726, the trackpad 34 is used in step 1004 to mark the actual location of the center of the bubble cloud with the crosshair 726. This visualization may be accompanied by the user detecting an audible signal within a predetermined range indicating the formation of the bubble cloud. The treatment output can then be deactivated in step 1005 by pressing the voltage knob 32. After the bubble cloud location has been marked (e.g., with the crosshair 726), the value of the distance the indicator is offset from the center of the planned treatment volume is displayed in field 1106, and the robotic arm 14 automatically and mechanically moves the displayed distance so that the bubble cloud occurs at the center of the planned treatment volume. In the case of a large offset in the Z axis, a notification may be displayed to warn the user of the possible impact on the binding medium level and the acceptability of the resistance threshold.If the user is concerned that the calibration offset may threaten the acceptability of these matters, the user can use the back button 1107 to return to step 840 of method 800 and from there make any necessary adjustments to the planned treatment volume. Optionally, as referred to herein, the system may instruct the user to re-mark the intersection of the patient's muscle layer and subcutaneous fat layer. After the treatment output has stopped, the confirm button 1108 can be selected. Alternatively, method 1000 may return to step 1003 to restart the voltage knob 32 and perform a new attempt to mark the center of the bubble cloud or verify that the cloud appears at the center of the planned treatment volume.

[0207]

[0226] After in vivo calibration, the voltage setting required to generate a bubble cloud at each survey point is evaluated in the order set by the application. As shown in Figure 42C, the first survey point among the survey points 739 (here, the -Z survey point) is designated by the application, and in step 1006, based on the completion of in vivo calibration, the robotic arm 14 navigates the treatment head 20 to position the treatment focus at the designated survey point, which is expected to be aligned with the treatment contour 728 or margin 732 according to the setting represented by the selected survey point 739. In step 1007, the voltage enable button 1103 is selected. In step 1008, the voltage knob 32 is used to increase the drive voltage of the treatment transducer 18 as shown by the indicator 1109 until a bubble cloud 1104 is generated in the ultrasound image 1102. In step 1010, the user visually (or audibly) confirms that the center of the bubble cloud appears at the focal point 726 (shown as a crosshair) at the intersection with the line of force 724, as shown in Figure 43A, where the treatment head 20 has already been navigated to the -Z and survey point 739, at which point the center survey point 739 is located. For each survey point 739, the voltage percentage that is increased by turning the voltage knob 32 to obtain the bubble cloud 1104 is recorded, as shown in the voltage indicator 1109. This process continues through all survey points 739. Figure 43B shows the recorded voltage percentage required to obtain a suitable bubble cloud at the +Y survey point. In one aspect of this disclosure, the final position to which the robotic arm 14 and treatment head 20 are navigated is the +Z position, but any position may be selected without departing from the scope of this disclosure. Alternatively, the application may have a specific sequence through which positions are navigated and through which a complete survey of the treatment volume is performed before the start of treatment.

[0208]

[0227] By rotating the voltage knob 32, the voltage on the indicator 1109 is increased to generate an acceptable bubble cloud 1104, which may be accompanied by the recognition of a clear audible sound generated by the therapeutic transducer 18 in step 1010, and after visual confirmation that the bubble cloud 1104 is located at the center of the focus 726 in step 1012 and that the voltage is acceptable in step 1013, the user can select to move to the next button 1110 in step 1016. If the user is not confident in the selected voltage, the voltage enable button 1103 may be selected again in the optional step 1014, and the voltage may be changed. This process is navigated to all investigation points 739, including the center point, and repeated until a voltage is applied to the tissue until an acceptable bubble cloud 1104 is generated, and the voltage is recorded as shown in Figure 44. In one embodiment, seven investigation points 739 are included, which are +Z, -Z, +Y, -Y, +X, -X, and the center point of the therapeutic volume. These seven survey points represent the outermost boundary or endpoint of the treatment volume, which is illustrated as a sphere. It should be understood that if the treatment volume contains other geometric shapes, a set of survey points, or a specified number of survey points, including the outermost endpoints of the treatment volume, may be required as test pulses. The voltage at each survey point 739 and the center point is stored in memory. These recorded voltage values ​​are used to interpolate the voltage values ​​used at each survey point of the treatment volume, as described above. As will be described in more detail below, the treatment volume consists of multiple separate treatment zones, each adjacent to one or more other treatment zones. By interpolating the voltage required for the formation of the bubble cloud 1004, sufficient voltage can be applied at all points within the volume without requiring a separate test for bubble cloud 1104 formation for each treatment zone. This system process is also referred to above as the threshold test.

[0209]

[0228] After navigating to the survey point 739 and all the centers of the volume defined by the survey point 739, and after the voltage at each location has been recorded, the confirm button 1111 becomes available. When selected, the UI 1100 updates to the details of the treatment volume 1113 shown in Figure 45. These include dimensions along each axis, total volume, minimum plan depth, maximum plan depth, and center point depth of the plan. The estimated treatment time for the treatment volume is also provided / displayed to the user. The estimated treatment time is calculated by the histotripsy system based on parameters including, but not limited to, treatment volume, voltage, cooling time, and focal location overlap. After review, the next button 1114 is selected in step 1020, and the treatment begins. If fusion is employed and the user desires, the ultrasound image 1102 can be replaced with a live fused image 1115 (e.g., live ultrasound fused with preoperative or perioperative images), as shown in Figure 46. Otherwise, the treatment proceeds to a simple live ultrasound image. Treatment begins at the deepest +Z investigation point within the patient. Panel 1116 includes a volume progress indicator 1118. The volume progress indicator 1118 shows the entire volume to be treated 1120 (e.g., the volume defined by the margin 732) and individual treatment zones / focal locations 1122.

[0210]

[0229] Each focal site is a volume of tissue that receives a histotripsy pulse from a therapeutic transducer 18 over a given duration. The energy or histotripsy pulse from the therapeutic transducer 18 bursts cells by cavitation of the tissue when the focal point is at focal site 1122, which is demonstrated by a bubble cloud 1108 and turns the cells into cell-free fragments that will be reabsorbed by the body. Non-thermal ablation of the volume to be treated 1120 is achieved by monitoring the amount of energy directed at a given focal site 1122 and by repeatedly turning the energy application on and off over a specific duration (as described herein). Naturally, the focal sites 1122 may have some overlap in volume to ensure complete treatment of the tissue.

[0211]

[0230] In step 1022, a query is made to determine whether all focal locations have been treated. If negative, the method proceeds to step 1024, in which the robotic arm 14 and the therapeutic transducer 18 move in a spiral manner, starting from the +Z investigation point 739 and proceeding to each consecutive focal location 1122, in the example shown herein. As described above, various different treatment patterns can be employed without departing from the scope of this disclosure. In this way, steps 1020-1024 are repeated until all focal locations 1122 have been treated and the entire resulting volume 1120 to be treated has been treated. The movement of the robotic arm 14 and the therapeutic transducer 18 is controlled by an application stored in a computing device such that, for each consecutive focal location 1122, the therapeutic transducer 18 is positioned on the patient so that the focal point 726 is centered on the focal location 1122, and a bubble cloud 1104 is generated for that particular focal location 1122. The duration of energy application and the period without energy application before moving to the next focal point 1122 are also controlled by the application as described herein.

[0212]

[0231] Figure 46 shows a fluoroscopic view of the volume 1120 to be treated. Figure 47 shows a top view of the volume 1120 to be treated, and Figure 48 shows a profile diagram of the volume to be treated. The view in which the volume to be treated is displayed can be changed by selecting one of the view selection buttons 1124. Figure 49A shows a fluoroscopic view of the progress of treatment as energy is applied to the continuum focal points 1122. Figures 49B to 49G show the continuum progress of treatment as the continuum focal points 1122 are treated until each focal point 1122 of the entire volume to be treated 1120 is treated. Note that if the image fusion process described above is skipped, the live fused image 1115 will not be displayed in Figures 49B to 49G when the application of treatment is shown.

[0213]

[0232] Once all focal points 1122 are treated and the result is positive in step 1022, the UL 1100 proceeds to the display shown in Figure 50. At this point, the user is instructed to deactivate the voltage knob 32 in step 1026. After deactivating the voltage knob 32, the user is instructed in step 1028 to use the robotic arm 14 to move the ultrasound probe 22 and visualize the entire volume to be treated in the ultrasound image. This can be done by using the freehand button 44 to manually move the treatment head 20 or by using the space mouse 36. The user may optionally add a comment in the comment field 1126 in step 1030, or simply select the end treatment session button 1130 in step 1132 and remove the treatment head 20 from the binding medium in step 1132.

[0214]

[0233] The treatment is now complete, but a record of the steps performed, the ultrasound images acquired during the procedure, and the resulting fusions are stored in memory for future analysis.

[0215]

[0234] When future treatments are planned, the system may be configured to recall treatment parameters, including, but not limited to, the posture and position of the robotic arm, the focus location of the treatment head and treatment transducer, bubble cloud offset, voltage threshold / required voltage, target depth, and the planned / treatment location and parameters. These parameters may be useful, for example, when additional treatments are to be performed within the same tumor or lesion, and / or when one or more treatment plans are intended to overlap with and / or be in the vicinity of the initial plan / treatment.

[0216]

[0235] For example, if adjacent treatments may be performed, the histotripsy system may be configured to recall recent treatment / planning parameters and automatically position (treatment head and robotic arm posture) at the start, end, or any treatment point in between (focus location or time reference).

[0217]

[0236] In another example, a histotripsy system is configured to allow the user to recall / move to a robotic posture used in a previous treatment. This would position the treatment head in the same location as before, assuming that the patient and treatment cart have not moved since the previous treatment. However, the user would need to recall the details of the previous treatment plan (XYZ diameters and margins) and then decide how to size and position the subsequent treatment plan. As disclosed previously, depending on the configuration, the system can store this information for recall.

[0218]

[0237] In yet another example, the histotripsy system may be configured to display previous treatment plan contours and plan overlays. Displaying previous treatment plan contours on the screen, along with a recall / navigation function (Option 1), provides the user with visual assistance in planning the overlap of the next treatment. This option also relies on the user considering the overlap of the previous treatment plan and tumor coverage to determine the best next treatment plan.

[0219]

[0238] In another example, the histotripsy system may be configured to plan all overlapping treatments before the first treatment delivery. If the user can identify and mark the tumors to be treated in 3D space, the histotripsy system can create and display recommended multiple treatment plans for the user to see. In some variations of this example, preoperative and perioperative CBCT may be used to enable this functionality.

[0220]

[0239] In another embodiment shown in Figure 52, the UI 1100 may include graphics 5201 to indicate cavitation detection for the user, in addition to “seeing or hearing” the bubble cloud. This may be presented to the user in various ways and locations on the display or UI. In one example, the UI may display a cloud or cavitation status 5202, which may include words such as “cavitation detected” or “cloud detected” to inform the user of the cloud or cavitation status. In a different example, the graphics may show an indicator 5203 for cavitation detection (“cloud”), which may display a color indicator for different statuses of cavitation, including when cavitation is “detected” or “maintained”. In the example in Figure 52, the indicator 5203 is color-coded to indicate “maintained” cavitation, matching the color coding of the cavitation status 5202 on the UI graphics. The indicator 5203 may include an oval or round shape, for example, configured to represent or highlight the contour of the cavitation extent, and may be presented together with a treatment contour 728 and margin 732. Depending on the embodiment, the color coding and / or indicators may differ between “detected” cavitation and “maintained” cavitation. In another example, the indicators may provide real-time feedback (total and / or per transducer channel if graphics of transducer faces and pulse channels are displayed). In these examples, the system and UI may enable this functionality for the user throughout all workflow steps (from system check to treatment), and / or, in another configuration, cavitation detection may be selectively disabled in use cases where it is preferable for the user to visually detect the clouds (e.g., during bubble cloud calibration).

[0221]

[0240] Furthermore, as part of the cavitation detection described above, as shown in Figure 53, the UI1100 may also include workflow steps, screens, and / or graphics to guide the user through one or more steps to acquire and receive data (e.g., detection) in order to enable aberration correction. In workflow step 5301 shown in the UI1100, the sustained bubble cloud cavitation is detected by the system (and shown to the user by the UI1100 in Figure 52). To initiate the activation of aberration correction, the user can activate the breath-hold and start acquisition button 5302. This process can adjust the transmission of the ultrasound waveform based on obstacles in the tissue or changing sound velocity to ensure that the cavitation is located at a desired position within the biological structure (e.g., within the treatment volume).

[0222]

[0241] Upon completion of treatment, various forms of procedure and treatment reports may be provided. These reports may include various forms of data, including patient and treatment contextual information (e.g., disease type, size, stage, location), planning parameters (size, location, target and margin contour dimensions in relation to target tissue / tumor, planning depth, planning position), energy setpoints (threshold and / or voltage setpoints across planning points, average voltage, etc.), and treatment details (e.g., time). This may further include UI, video recordings of the UI, or screenshots from the procedure. This information / data may also include any information / data incorporated and / or used for pre-procedure simulations and / or the aforementioned patient registration process. These various reports may be exportable to electronic health records or databases, as well as to local networks, media, and / or other devices.

[0223]

[0242] In some examples, referring to Figure 56, the system and UI1100 may be configured modularly, allowing the user to select one or more workflows based on the procedure application, indication and / or anatomical location 5501 (e.g., abdomen, liver, kidney, pancreas, spleen, upper or lower GI, cardiothorax, lung, breast, thyroid, head and neck, nerve / cranial, spine, etc.), based on the desired imaging 5502 (e.g., ultrasound only, fusion, CBCT, etc.), based on the room setup 5503, and / or based on which treatment head 5504 is selected, and / or to allow skipping a particular workflow step if that particular workflow step has already been completed within an acceptable time (e.g., system check).

[0224] Outline Architecture

[0243] Next, we refer to Figure 51, a schematic diagram of a histotripsy system 1200 configured for use with the methods of the present disclosure, including methods 400 and 600. The system 1200 may include a workstation 1101 (computing device). The workstation 1101 may be housed in a cart 12, as described above, and is connected to an ultrasound imaging device 1015 (e.g., an imaging probe 22) and an ultrasound therapeutic device (e.g., a therapeutic transducer 18). Depending on the embodiment, the system may be connected to an X-ray based imaging system, including a cone-beam CT. The workstation 1001 may include memory 1202, a processor 1204, a display 1206 (e.g., a display 24 showing UI 200, 500, 700, 1100), and an input device 1210. The processor or hardware processor 1204 may include one or more hardware processors. The workstation 1201 may optionally include an input / output module 1212 and a network interface 1208. Depending on the embodiment, this may include streaming and / or connectivity that enables remote access to the system for querying, searching and / or receiving logs or configuration files for maintenance / support and / or for maintaining software or embedded solutions for the system and / or one or more subsystems (such as generators, robotic arms and control systems). Memory 1202 can store application 1218 and image data 1214. Application 1218 may include instructions that can be executed by processor 1204 to perform the methods of this disclosure, including methods 50, 100, 400, 600 and 1000.

[0225]

[0244] Application 1218 may further include a user interface 1216 (e.g., UI200, 500, 700, 1100). Image data may include preoperative CT and MRI scans or other images, ultrasound image data, and 2D or 3D reconstructions derived from the ultrasound image data, including multimodal computer vision and fusion models. Depending on the embodiment, including when connected to a cone-beam CT, the UI may include graphics and instructions to guide the user through setup, import, registration, and navigating to the desired target. Processor 1204 may be coupled with memory 1202, display 1206, input device 1210, output module 1212, network interface 1208, and ultrasound imaging device 1215. Workstation 1201 may be a stationary computing device such as a personal computer, or a portable computing device such as a tablet computer. Workstation 1201 may incorporate multiple computer devices.

[0226]

[0245] For example, Figure 54 shows a UI 1100 that includes a workflow for positioning the CBCT machine 5301 around a patient to acquire CT images of the patient and / or target tissue. This UI may include workflow steps / user inputs 5302-5305, which may include positioning the treatment head of the histotripsy system away from the CBCT bore (5302), acquiring the patient's CBCT scan (5303), importing the scan, and identifying the target tissue (5304-5305).

[0227]

[0246] In Figure 55A, workflow steps 5401-5402 guide the user to identify the center of the target lesion in each view of the imported CT by the target center, as shown in workflow step 5403. The target center 5405 is shown above each of the CT images 5406 as positioned by the user. The user may optionally add anatomical markers to the images, as shown in workflow step 5404.

[0228]

[0247] In Figure 55B, workflow steps 5407-5408 guide the user to move the treatment head to align it with the target center identified in the previous UI diagram. The user can press the "Move to Point" or "Move to Center" button 5409 to align the treatment head with the target center. Optionally, the user can manipulate the space mouse (or hardware input / joystick / mouse) to freely drive the treatment head for positioning if it is necessary to avoid collisions with obstacles or (e.g., the patient or binding vessel).

[0229]

[0248] Memory 1202 may include any non-temporary computer-readable storage medium for storing software, which is executable by the processor 1204 and can control the operation of the workstation 1201, and, depending on the embodiment, can also control the operation of the ultrasound imaging device 1215 and the ultrasound therapeutic device 1218, including data and / or instructions. In embodiments, memory 1202 may include one or more storage devices, such as solid-state storage devices, for example, flash memory chips. Alternatively, or in addition to one or more solid-state storage devices, memory 1202 may include one or more mass storage devices connected to the processor 1204 via a mass storage controller (not shown) and a communication bus (not shown).

[0230]

[0249] The description of computer-readable media included in this specification refers to solid-state storage, but those skilled in the art should understand that a computer-readable storage medium can be any available medium accessible by processor 1204. That is, a computer-readable storage medium can include non-transitory volatile and non-volatile removable and non-removable media implemented by any method or technology for storing information such as computer-readable instructions, data structures, program modules, or other data. For example, a computer-readable storage medium can include RAM, ROM, EPROM, EEPROM, flash memory, or other solid-state memory technologies, CD-ROM, DVD, Blue-Ray, or other optical storage, magnetic cassettes, magnetic tapes, magnetic disk storage, or other magnetic storage devices, or any other medium that can be used to store desired information and is accessible by workstation 1201.

[0231]

[0250] When application 1218 is executed by processor 1204, it can cause user interface 1216 to be presented on display 1206. User interface 1216 can be configured to present various screens to the user, including any of FIGS. 4 to 13, FIGS. 15, FIGS. 17 to 22, FIGS. 24 to 32, FIGS. 34 to 40, FIGS. 42 to 50.

[0232]

[0251] The network interface 1208 may be configured to connect to a network such as a local area network (LAN) consisting of wired and / or wireless networks, a wide area network (WAN), a wireless mobile network, a Bluetooth network, and / or the Internet. The network interface 1208 may be used to connect the workstation 1201 to an imaging device 1215 or a therapeutic device 1217. The network interface 1208 may also be used to receive image data 1214. The input device 1210 may be any device by which a user can interact with the workstation 1201, such as a mouse, keyboard, foot pedal, touchscreen, and / or audio interface. The output module 1212 may include any connection port or bus, such as a parallel port, serial port, Universal Serial Bus (USB), or any other similar connection port known to those skilled in the art. Those skilled in the art will see from the above and by referring to the various figures that certain modifications to the present disclosure can be made without departing from the scope of the present disclosure.

[0233]

[0252] While detailed embodiments are disclosed herein, these embodiments are merely examples of the disclosure, which can be implemented in various forms and manners. Therefore, certain structural and functional details disclosed herein should not be construed as limiting, but rather as the basis for the claims and as a basis for instructing those skilled in the art to employ the disclosure in various ways with virtually any suitable detailed structure. Those skilled in the art will conceive of other modifications within the scope and spirit of the claims appended herein.

Claims

1. Ultrasound imaging system and, An ultrasound therapeutic transducer coupled to the ultrasound imaging system, The ultrasound imaging system and the ultrasound therapeutic transducer are configured to be positioned relative to the patient and the treatment site by a robotic arm, A display operably connected to the aforementioned ultrasound imaging system, Memory for storing instructions, The instruction includes, and when the instruction is executed by a processor operablely connected to the memory, Receiving real-time ultrasound images from the aforementioned ultrasound imaging system, The live ultrasound image is presented on the user interface of the display, Identify the target, Through the user interface, input is received to modify the shape of the target contour around the treatment volume in the live ultrasound image. In the user interface, a target contour line representing the target contour is displayed on the ultrasound image. The user interface receives input for the size of the margin around the target region, In the user interface, margin contour lines representing the margin contour are displayed on the ultrasound image. Determine the survey points where the X, Y, and Z axes bisect the margin lines in the XZ and YZ planes. The ultrasonic therapy transducer receives an input that drives the transducer to a location where its focal point is one of the survey points. A histripsy system for determining whether the resistance to movement of the aforementioned ultrasound therapeutic transducer exceeds a threshold.

2. A histotripsy system according to claim 1, wherein input for changing the shape of the treatment contour around the treatment volume is received via the user interface in the XZ and YZ planes of a live ultrasound image.

3. A histotripsy system according to claim 1, wherein the input for driving the ultrasound therapeutic transducer is received via the user interface of the display.

4. The histotripsy system according to claim 1, wherein the input for driving the ultrasound therapeutic transducer is received for each investigation point.

5. The histotripsy system according to claim 4, wherein if it is determined that the resistance to the movement of the ultrasound therapeutic transducer does not exceed a threshold while it is being driven to reach all of the survey points, the planned treatment is accepted and stored in the memory.

6. The histotripsy system according to claim 4, wherein when it is determined that the resistance to the movement of the ultrasonic therapeutic transducer exceeds a threshold while it is being driven to reach any of the survey points, the instruction stored in memory and executed by the processor causes the user interface to present a mitigation instruction.

7. A histotripsy system according to claim 1, further comprising presenting the contour lines and the representations of the survey points in separate fields of the user interface.

8. A histotripsy system according to claim 7, wherein the input for driving the therapeutic transducer is received via the representation of the contours and survey points in the separate fields of the user interface.

9. The histotripsy system according to claim 7, further comprising an indicator shown on the investigation point of the representation in the separate field on the user interface, wherein the indicator indicates that the therapeutic transducer has moved to a location where the focus coincides with the investigation point.

10. The histotripsy system according to claim 1, wherein when the instruction is executed by the processor, the histotripsy system receives input of the location of the intersection of the muscle layer and the fat layer in the live ultrasound image.

11. A histotripsy system according to claim 1, wherein when the instruction is executed by the processor, it triggers the activation of a knob, and when the knob is operated, it adjusts a parameter displayed on an indicator on the user interface.

12. A histotripsy system according to claim 11, wherein the knob adjusts the contour along the X, Y, and Z axes.

13. The histotripsy system according to claim 11, wherein the knob adjusts the size of the margin around the contour.

14. A histotripsy system according to claim 11, wherein the knob adjusts the focal location of the therapeutic transducer.

15. A method for planning histotripsy treatment, The steps include displaying a live ultrasound image on the user interface, The steps include moving the ultrasound assembly in the live ultrasound image to a mark on the patient from which the treatment area within the patient can be observed, The steps include: displaying contour lines around the treatment volume in the live ultrasound image on the user interface; The steps include adjusting the contour lines in the live ultrasound image, A step of identifying survey points where the X, Y, and Z axes intersect the contour lines in the XZ and YZ planes, The steps include displaying a margin around the aforementioned contour line, A step of displaying the focus of a therapeutic transducer, wherein the therapeutic transducer is a component of the ultrasound assembly; The steps include driving the ultrasound assembly such that the focus of the therapeutic transducer coincides with at least one of the investigation points, The steps include detecting resistance to the movement of the ultrasonic assembly as the ultrasonic assembly moves to reach the at least one inspection point, Methods that include...

16. A method according to claim 15, further comprising the step of comparing the resistance to movement with a threshold.

17. A method according to claim 15, further comprising the step of modifying the shape of the contour line around the treatment area in the XZ plane and the YZ plane of the live ultrasound image.

18. The method according to claim 15, wherein the ultrasonic assembly is driven to each inspection point by robotic control.

19. A method according to claim 18, wherein if it is determined that the resistance to the movement of the therapeutic transducer does not exceed a threshold while it is being driven to reach each of the investigation points, the planned treatment is accepted and stored in memory.

20. A method according to claim 19, further comprising the step of receiving an indication of the location of the intersection of the muscle layer and the fat layer in the live ultrasound image.

21. A treatment method for histotripsy, The steps include navigating the therapeutic transducer to align the focus with the center of the planned treatment volume, Steps to activate a histotripsy pulse, The steps include increasing the voltage associated with the histotripsy pulse until a bubble cloud / acoustic cavitation occurs, The step of marking the center of the aforementioned bubble cloud, A step of navigating the therapeutic transducer to a plurality of survey points around the planned therapeutic volume, wherein at each survey point, the voltage associated with the histotripsy pulse is activated and increased until a bubble cloud is generated / formed, A step of initiating an automated treatment plan, wherein the treatment transducer is robotically driven to a plurality of focal locations within the planned treatment volume, and the histotripsy pulse is applied at each focal location. Methods that include...

22. A method according to claim 21, further comprising the step of interpolating the ultrasonic energy required for each focal point based on the voltage applied at each of the survey points and at the center of the planned treatment volume.

23. The method according to claim 22, wherein the therapeutic transducer is driven to each focal site in a sequential pattern until all focal sites in the planned therapeutic volume receive individualized histotripsy pulses.

24. A method according to claim 21, wherein it is confirmed that the bubble cloud generated at each inspection point coincides with the focus of the therapeutic transducer.

25. A method according to claim 21, further comprising the step of deactivating a voltage knob associated with the source of the therapeutic energy, following the completion of the automated treatment plan.

26. A method according to claim 21, further comprising the step of confirming that all focal locations have received a histotripsy pulse.

27. A method according to claim 26, further comprising the step of visualizing the planned treatment volume after the completion of the treatment plan in order to confirm complete treatment.

28. A method according to claim 27, wherein the visualization is performed using an ultrasonic imaging probe.

29. The method according to claim 21, wherein the first of the plurality of survey points to which the therapeutic transducer is navigated is the -Z survey point.

30. A method according to claim 21, further comprising the step of calculating the offset between the center of the bubble cloud and the focus of the therapeutic transducer.

31. A method according to claim 30, further comprising the step of using the offset to calibrate the placement of the therapeutic transducer so that it reaches each investigation point.

32. A method according to claim 21, further comprising the step of displaying the automated treatment plan on a user interface, wherein the automated treatment plan defines one or more of the volume to be treated, the depth of the plan, and the margins.

33. A method according to claim 21, wherein the user interface displays a treatment indication at each focal location of the planned treatment volume following the application of a histotripsy pulse to the focal locations.

34. A method according to claim 33, wherein the user interface displays an indication of which focal location of the planned treatment volume is currently receiving a histotripsy pulse.

35. The method according to claim 21, further comprising a user interface for displaying an ultrasound image acquired by an ultrasound imaging transducer, wherein the ultrasound image shows at least a portion of the planned treatment volume.

36. A method according to claim 35, wherein when the histotripsy pulse is applied, the bubble cloud can be seen in the ultrasonic image.

37. A method according to claim 35, further comprising the step of showing one or more of the focus, the planned treatment volume, margins, or the sound field of the therapeutic transducer on the ultrasound image.

38. A method according to claim 35, wherein ultrasound imaging is continued throughout the entire automated treatment plan so that visualization of histotripsy pulses for each focal location is visualized.

39. The method according to claim 38, wherein the ultrasound image is a fused ultrasound image shown in combination with a preoperative image set.

40. A method according to claim 21, further comprising the steps of detecting resistance to movement of the therapeutic transducer and displaying an indicator of the resistance on a user interface.

41. A method of fusing images, Steps include navigating the combined imaging and therapeutic transducer assembly to a location on the patient that enables visualization of the region of interest, The steps include performing an ultrasound sweep using the imaging transducer of the composite imaging and therapeutic transducer assembly to capture many ultrasound images, Marking registration points in the ultrasound image obtained from the aforementioned ultrasound sweep, Marking registration points in images from the preoperative image set, The steps include fusing the preoperative image set with the ultrasound image from the ultrasound sweep in order to form a fused image, Steps to review the fused image, Steps to accept fusion, A method comprising the step of displaying a live ultrasound image fused with the preoperative image set on a user interface.

42. A method according to claim 41, further comprising the step of verifying that the composite imaging and therapeutic transducer assembly is located substantially in the center of the region of interest in multiple planes.

43. A method according to claim 41, further comprising the step of marking a plurality of registration points in the image from the ultrasound sweep and a plurality of registration points in the preoperative image set.

44. A method according to claim 41, further comprising the step of initiating the patient to hold their breath before performing the ultrasonic sweep.

45. A method according to claim 41, further comprising the step of adjusting the orientation and position of the combined imaging and therapeutic transducer assembly in order to optimize the visualization of the region of interest by the imaging transducer.

46. A method according to claim 45, further comprising the step of rotating the imaging transducer of the composite imaging and therapeutic transducer assembly by 90 degrees to confirm the visualization of the region of interest.

47. A method according to claim 41, further comprising the step of displaying the ultrasonic image captured during the ultrasonic sweep.

48. A method according to claim 41, further comprising the step of editing the ultrasound image captured during the ultrasound sweep.

49. A method according to claim 48, wherein the image remaining after editing the image is only the image showing the region of interest.

50. A method according to claim 41, wherein the registration point placed in the ultrasound image corresponds to the registration point in the preoperative image set and is placed on an anatomical landmark that appears in both the ultrasound image and the preoperative image set.

51. A method according to claim 50, further comprising the step of determining whether sufficient anatomical landmarks were identified in the ultrasound image and the preoperative image set.

52. A method according to claim 51, further comprising the step of locating at least one registration point in a plurality of ultrasound images and at least one registration point in a plurality of images from the preoperative image set.

53. A method according to claim 41, further comprising the step of adjusting the position of the registration point in the ultrasound image or the position of the registration point in the preoperative image set.

54. A method according to claim 41, further comprising the step of adjusting the registration of the images from the ultrasound sweep with respect to the preoperative image set by dragging or rotating at least one image from the vertical preoperative image set relative to the images from the ultrasound sweep.

55. A method according to claim 41, further comprising the step of verifying the alignment of the patient's biological structures in the live ultrasound image and the preoperative image set.

56. A method according to claim 55, further comprising the step of rotating the imaging transducer of the composite imaging and therapeutic transducer assembly by 90 degrees in order to verify the alignment.

57. A method according to claim 41, further comprising the step of adjusting the displayed live ultrasound image fused with the preoperative image set.

58. A system configured for use according to claim 41.

59. A method for planning the treatment of histotrypsy, In the first aspect, the step is to visualize the target treatment volume using an ultrasound imaging system, The steps include displaying a target contour around the treatment volume in an ultrasound image generated by the ultrasound imaging system, The steps include adjusting the target contour around the treatment volume on the first surface, The first step is to confirm that there are substantially no obstructions in the acoustic path of the therapeutic transducer, In the second aspect, the step of visualizing the target treatment volume using the ultrasound imaging system, A step of displaying the target contour around the treatment volume in a second ultrasound image generated by the ultrasound imaging system, The steps include adjusting the target contour around the treatment volume on the second surface, The second step is to confirm that there are substantially no obstructions in the acoustic path of the therapeutic transducer, Methods that include...

60. A method according to claim 59, wherein the target contour of the first surface and the target contour of the second surface define a volume for treatment.

61. A method according to claim 60, further comprising the step of displaying a margin around the treatment volume.

62. A method according to claim 61, further comprising the step of defining a plurality of survey points of the treatment volume.

63. The method according to claim 62, wherein the inspection point is located at a point where the axis intersects the margin, along the center of the treatment volume and three orthogonal axes extending outward from the center of the treatment volume.

64. The method according to claim 63, wherein the axes are X, Y, and Z.

65. The method according to claim 64, wherein the first surface is a YZ plane.

66. The method according to claim 65, wherein the second surface is the XZ plane.

67. A method according to claim 66, wherein the step of adjusting the target contour of the first surface is to adjust the diameter of the treatment volume along the Y axis and the diameter of the treatment volume along the Z axis.

68. A method according to claim 67, further comprising the step of confirming that the target contour of the first face is located at the center of the YZ plane and the target contour of the second face is located at the center of the XZ plane.

69. A method according to claim 62, further comprising the step of receiving a selection of one of the survey points.

70. A method according to claim 69, further comprising the step of robotically driving the therapeutic transducer to the selected investigation point.

71. A method according to claim 70, further comprising the step of detecting resistance to movement of the therapeutic transducer while it is moving to the selected investigation point.

72. A method according to claim 71, wherein if the detected value of the resistance exceeds a threshold, an indicator or the threshold is shown.

73. A method according to claim 72, further comprising the steps of detecting whether the value of the resistance exceeds a second threshold, and stopping the robotic controlled movement of the therapeutic transducer.

74. A method according to claim 73, further comprising the steps of adjusting the target contour or margin of the treatment volume or the focus of the treatment transducer, and driving to the investigation point.

75. A method according to claim 71, further comprising the step of receiving confirmation that all inspection points have been driven.

76. A method according to claim 75, further comprising the step of receiving an indication of the location of the intersection of the muscle layer and the fat layer via a user interface.

77. A method according to claim 75, further comprising the step of receiving verification that the therapeutic volume is within the target contour of the first surface and the target contour of the second surface throughout the entire respiratory cycle.

78. A method according to claim 75, wherein the level of the bonding medium in the bonding vessel in which the therapeutic transducer is located is sufficient to ensure ultrasonic bonding at all investigation points.

Images