Alignment control systems and methods for neuromodulation delivery systems

Abstract

The present discussion relates to structures and devices that facilitate application of an ultrasound therapy beam (106) to a target anatomical region in a replicable manner. In certain aspects, an alignment controller (30) can be used to analyze an image generated by an ultrasound transducer. The alignment controller (30) may then send a communication to indicate that an energy application device is positioned to provide treatment to the target region, or if the device needs to be repositioned. Alignment control of the energy application device provides a guided, repeatable aiming of the target anatomical region, even in a non-clinical environment.

Description

Background Art

[0001] The subject matter disclosed herein relates to an alignment control system for targeting and / or dosing an area of ​​interest in a human subject via application of neuromodulatory energy to induce a targeted physiological outcome. Specifically, a system for positioning and orienting an energy application device enables an untrained person to locate an anatomical target to provide treatment to a human subject.

[0002] Neuromodulation has been used to treat a variety of clinical conditions. However, targeting specific tissues via neuromodulation can be challenging. For example, the exact focusing of neuromodulation energy can vary based on individual human subject anatomy. Certain subjects may have variations in organ size or location relative to other subjects based on their height, weight, age, gender, clinical condition, etc., which may affect targeting when using various neuromodulation techniques.

[0003] In the case of neuromodulation using ultrasound devices, other common challenges may be related to the difficulty of repeatedly delivering accurate and consistent ultrasound treatments at prescribed doses in the context of a treatment regimen involving multiple repeated treatments of the treatment area. Further, such treatments may be difficult for minimally trained individuals to administer, necessitating that human subjects enter a clinical setting and / or be treated by a medically trained individual for each treatment session. Therefore, human subjects self-administering treatment or treatment in a home setting is generally not considered feasible for ultrasound-based neuromodulation regimens.

[0004] For example, when a clinician administers conventional ultrasound, the clinician places the probe on the body and manipulates it with all degrees of freedom (DOF) until the probe reaches the target scan plane. In contrast, in a human subject or self-administered home setting, an untrained user has little ability to understand ultrasound images, and even if they do, they have no ability to judiciously manipulate a handheld ultrasound probe to find the target. Such problems make it impractical to self-administer precision targeted ultrasound-based treatments using conventional methods, particularly in a home setting. Summary of the invention

[0005] The embodiments disclosed herein are not intended to limit the scope of the claimed subject matter, but rather these embodiments are intended only to provide a brief overview of possible embodiments. In fact, the present disclosure may include a variety of forms that may be similar to or different from the embodiments described below.

[0006] In one embodiment, a neuromodulation delivery system includes an energy application device and an alignment controller. The alignment controller is configured to perform actions including: receiving image data from the energy application device, wherein the image data includes an image of internal tissue based on a current position and orientation of the energy application device relative to a subject; and determining an alignment score of the energy application device relative to an anatomical target based on the image data. Further, the alignment controller is configured to provide a control signal in response to the alignment score to maintain or change one or both of the current position or orientation of the energy application device.

[0007] In another embodiment, a method includes receiving, via a processor, time-series image data at a current position and orientation relative to a subject from an energy application device, wherein the time-series image data includes images of internal tissue of the subject at the current position and orientation over time; in addition, the method includes determining, via the processor, an alignment score of the energy application device relative to an anatomical target over time based on the image data, and comparing, via the processor, the alignment score within a time interval corresponding to the time-series image data at the current position and orientation with a predicted alignment score for the time interval at one or both of additional positions or orientations; further, the method includes providing a control signal based on the comparison to maintain or change one or both of the position or orientation of the energy application device.

[0008] In another embodiment, a tracking system includes one or more processors and a memory, wherein the one or more processors are configured to execute instructions stored on the memory to perform actions including receiving image data from an energy application device, wherein the image data includes an image of internal tissue based on a current position and orientation of the energy application device relative to a subject. The actions also include receiving target image data, the target image data including an anatomical target and corresponding to the internal tissue of the subject; identifying the anatomical target in an image frame of the image data and tracking the anatomical target in subsequent image data frames of the image data; and determining an alignment score of the energy application device relative to the anatomical target based on the image data. Additionally, the actions include comparing the alignment score to a threshold value relative to the anatomical target; and providing a control signal to maintain or change one or both of the position or orientation of the energy application device based on the comparison of the alignment score to the threshold value. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] These and other features, aspects and advantages of the present invention will be better understood when the following detailed description is read with reference to the accompanying drawings, in which like characters refer to like parts throughout the several views, and in which:

[0010] Figure 1is a block diagram of a neuromodulation delivery system according to an embodiment of the present disclosure;

[0011] Figure 2 According to the embodiments of the present disclosure Figure 1 Schematic diagram of the probe of the neuromodulation delivery system;

[0012] Figure 3 According to the embodiments of the present disclosure Figure 1 A flow chart of a method for controlling alignment of a probe of a neuromodulation delivery system;

[0013] Figure 4 According to the embodiments of the present disclosure, Figure 1 An illustration of a user interface for alignment control of a probe of a neuromodulation delivery system;

[0014] Figure 5 According to the embodiments of the present disclosure Figure 1 A flowchart of a method for delivering a therapeutic dose through a probe of a neuromodulation delivery system;

[0015] Figure 6 According to an embodiment of the present disclosure, Figure 1 An illustration of a user interface of a probe of a neuromodulation delivery system for therapeutic dosing;

[0016] Figure 7 is a schematic diagram of tracking over time using a therapeutic transducer with one-dimensionally adjustable focus in one dimension according to an embodiment of the present disclosure;

[0017] Figure 8 is a timing diagram of portal vein motion within ultrasound image data and inertial measurement unit (IMU) sensor data according to an embodiment of the present disclosure;

[0018] Fig. 9A is a schematic diagram of time-lapse tracking using a fixed two-dimensional imaging transducer and a mechanically oscillating therapeutic transducer with external motion adjustment according to an embodiment of the present disclosure;

[0019] Fig. 9B is a schematic diagram of tracking over time using a fixed two-dimensional imaging transducer and a mechanically oscillating therapy transducer with internal motion regulation according to an embodiment of the present disclosure;

[0020] Fig. 10A is a schematic diagram of tracking over time using a two-dimensional imaging transducer coupled to a therapeutic transducer with external motion modulation according to one embodiment of the present disclosure;

[0021] Fig. 10Bis a schematic diagram of tracking over time using a two-dimensional imaging transducer coupled to a therapeutic transducer with internal motion modulation according to one embodiment of the present disclosure;

[0022] Fig.11 is a schematic diagram of tracking over time using a single linear transducer for imaging and therapy according to one embodiment of the present disclosure;

[0023] Fig. 12A is a schematic diagram of three-dimensional tracking with an azimuth view having active one-dimensional focus according to one embodiment of the present disclosure;

[0024] Fig. 12B is a schematic diagram of three-dimensional tracking with an orthographic view having active one-dimensional focus according to one embodiment of the present disclosure;

[0025] Fig.13 is an illustration of a transducer face including a two-dimensional imaging array and a two-dimensional therapy array according to one embodiment of the present disclosure; and

[0026] Fig.14 is a schematic diagram of an example of a fixed arrangement of two-dimensional dual transducers for imaging and therapy according to an embodiment of the present disclosure. DETAILED DESCRIPTION

[0027] One or more specific embodiments will be described below. In order to provide a concise description of these embodiments, not all features of an actual implementation are described in the specification. It should be understood that in the development of any such actual implementation, as in any engineering or design project, many implementation-specific decisions must be made to achieve the developer's specific goals, such as complying with system-related and business-related constraints that may vary from implementation to implementation. In addition, it should be understood that such development efforts may be complex and time-consuming, but are still routine tasks for design, fabrication, and manufacturing for ordinary technicians who benefit from this disclosure.

[0028] Any example or illustration given herein should not be regarded as the constraint, restriction or clear definition of any one or more terms utilized by it in any way.On the contrary, these examples or illustrations should be regarded as describing about various specific embodiments and are only exemplary.It will be understood by those of ordinary skill in the art that any one or more terms used by these examples or illustrations will cover other embodiments that may or may not be provided together with it or provided elsewhere in this specification, and all such embodiments are intended to be included in the scope of the one or more terms.The language specifying such non-limiting examples and illustrations includes but is not limited to: "for example", "for example", "such as", "such as", "including", "in certain embodiments", "in some embodiments" and "in one embodiment".

[0029] As discussed herein, one problem that may arise with a treatment technique involving multiple sessions of targeted ultrasound neuromodulation (e.g., 1x per day, 3x per week, 1x per week) is the need to provide consistent, correct alignment for each session. In the case of treatment that can be performed by individuals (including human subjects) with little or no medical training in a non-clinical environment (e.g., at home), it is desirable to provide such aiming and alignment guidance in as simple a form as possible. For example, it may be desirable to provide aiming and / or alignment assistance without manual guidance based on a displayed image and / or in the case of removing or minimizing common sources of user error or frustration. In addition, although it is not feasible to "one size fits all methods" due to the large variations in the internal and external anatomical structures of human subjects, it can be further useful to use a type of alignment device suitable for use in a wide range of subject populations. With this in mind, the methods, structures, and techniques described herein include an ultrasound treatment alignment device with customizable elements that guide the user and / or automatically position the treatment device. The system and device are customizable to address larger fluctuations in the entire human subject population, while also being suitable for non-clinical environments (e.g., home use of human subjects).

[0030] A human subject may aim a therapeutic device at an anatomical target within human tissue (e.g., an anatomical target for therapeutic treatment), and the therapeutic device may include alignment controls to place the therapeutic device at a position and orientation that can provide effective treatment to the anatomical target. To account for the uniqueness of each human subject's internal anatomy, the alignment device may include angle and / or orientation adjustments (e.g., pan, tilt, rotation) and configurable depth to nominally direct and focus the therapeutic beam at the internal anatomical target area. Further, in some embodiments, after determining the location of the target within one or more image frames, the system may deliver treatment at the location by electronically steering the therapeutic beam to the anatomical target while applying a therapeutic dose. Alternatively, a therapeutic transducer having appropriate therapeutic transducer characteristics (e.g., power handling, frequency range, geometry, etc.) and / or a probe cover having appropriate probe cover characteristics (e.g., angle adjustment, attenuation adjustment (e.g., standoff height and / or composition), other geometries or features for focusing, shaping, or aiming the beam, etc.) can be selected and employed to direct the therapeutic beam to a determined location when applying a therapeutic dose.

[0031] In a further example, certain embodiments discussed herein utilize an alignment controller of the system to enable a user to position an energy application device to direct the energy application device to an area where an anatomical target (e.g., an anatomical target predetermined by a clinician) of a human subject is located. The alignment controller may receive sensor data from a plurality of sensors that may monitor the movement of the human subject throughout the respiratory cycle and / or collect image frame data of the internal tissue of the human subject. The alignment controller may send signals to one or more components of the energy application device to steer and / or focus the treatment beam to correspond to the movement of the human subject relative to the anatomical target predefined therefor. This may enable the treatment dose to be accurately delivered during the surface movement of the subject's body and the internal movement caused by the subject's respiratory cycle. The alignment controller may utilize the image data over time to send one or more signals to adjust the position (e.g., two-dimensional plane, three-dimensional position) and orientation (e.g., pan, tilt, rotation) of the treatment beam of the energy application device over time to correspond to the position of the anatomical target in the subject's body. Alignment may be achieved manually, such as by an alignment signal that may be displayed on a display of the device or an electronic device of the subject for the subject to follow to reposition the energy application device. In addition, the alignment can be automatic, such that the alignment controller can send a signal to electronically steer and / or focus the energy application device to a desired position and / or orientation. Upon receiving the signal, the automated controller can automatically adjust the position of the probe module relative to the user (e.g., on or outside the user), adjust the internal position of the probe transducer within the probe housing, or both, to improve alignment with the anatomical target. The automated controller can perform internal and / or external adjustments of the probe module until the alignment meets the aiming and / or threshold alignment.

[0032] With this in mind, Figure 1 Depicted are examples of neuromodulation systems that are configured to deliver neuromodulation energy as part of a treatment regimen and that can be used with alignment and / or positioning devices or structures as discussed herein. Specifically, Figure 1 1 is a schematic diagram of a system 10 for neuromodulation to achieve a neuromodulatory effect, such as neurotransmitter release and / or activation of a synaptic moiety (e.g., presynaptic cell, postsynaptic cell) in response to application of energy. The system 10 includes a pulse generator (as part of a therapy module 12) coupled to an energy application device (depicted as one or more therapy transducers 24 as part of a probe module 14). The energy application device is configured to receive energy pulses, such as via a wire or wireless connection, or otherwise generate energy pulses that, in use, are directed to an anatomical target site of a subject, which in turn results in a targeted physiological outcome.

[0033] In certain embodiments, the energy application device and / or the pulse generator may communicate wirelessly, for example, with a controller, which in turn may provide instructions to the pulse generator. As discussed herein, the energy application device may be an extracorporeal device, for example, operable to apply energy transcutaneously or non-invasively from a location outside the subject's body, and in certain embodiments, may be integrated with the pulse generator and / or controller. In embodiments where the energy application device is an extracorporeal device, the energy application device may be operated by a caregiver or subject and positioned at a point on or above the subject's skin so that energy pulses are delivered transcutaneously to the desired internal tissue. Once positioned to apply energy pulses to an area of ​​interest, the system 10 may initiate neuromodulation of one or more neural pathways to achieve a targeted physiological outcome or clinical efficacy. In some embodiments, the system 10 may be implemented so that some or all of the elements may communicate with each other in a wired or wireless manner.

[0034] The system 10 may include an alignment controller 30 that evaluates characteristics indicative of placement and orientation of the energy application device. Based on such evaluations, the delivery of therapeutic ultrasound energy may be automatically and / or manually altered, adjusted, or manipulated to achieve a prescribed therapeutic outcome. By way of example, when a therapeutic dose is applied, the therapeutic beam may be electronically steered to a target location. Additionally or alternatively, instructions or guidance may be provided to a user via, for example, an audible indicator, a visual indicator, or a tactile indicator to provide guidance regarding placement and / or orientation of the energy application device.

[0035] Energy application equipment as provided herein can provide energy pulses as part of a treatment regimen to apply a prescribed amount of energy according to various adjustment parameters. For example, adjustment parameters can include various stimulation time modes ranging from continuous to intermittent. In the case of intermittent stimulation, energy is delivered at a specific frequency for a period of time during the signal on time. After the signal on time is a period of time without energy delivery, referred to as the signal off time. Adjustment parameters can also include stimulation application frequency and duration. The application frequency can be continuous or delivered in different time periods, such as within a day or a week. In addition, the treatment regimen can specify the time of applying energy in a day or relative to the time of eating or other activities. The treatment duration causing the targeted physiological result can be sustainable for different time periods, including but not limited to from a few minutes to a few hours. In certain embodiments, the treatment duration with a specified stimulation mode can be sustainable for one hour, repeated at intervals such as 72 hours. In certain embodiments, energy can be delivered at a higher frequency (such as every three hours) for a shorter duration, such as 30 minutes. According to adjustment parameters, such as treatment duration, frequency and amplitude, the application of energy can be adjustable to achieve the desired physiological or therapeutic results.

[0036] Considering the foregoing background, the following describes in more detail Figure 1Additional features shown. Specifically, various aspects and components of the specific implementation of system 10 are shown as corresponding to certain functions described above. As described above, Figure 1 The block diagram of shows a treatment module 12 and a probe module 14 that can be used to perform the treatment functions described herein. An imaging module 16 is also shown, but it should be understood that in certain embodiments, such an imaging module 16 may not be present. In such alternative embodiments, the analysis performed on the imaging data can be performed on unreconstructed (i.e., raw) imaging data or on image data that is reconstructed but not displayed. By way of example, the administration and / or control of treatment based on data acquired using an imaging transducer or at an imaging module 16 can be based on a reconstructed image (e.g., features within the reconstructed image data) or based on ultrasound features present in the unreconstructed image data.

[0037] Starting with the probe module 14, in the depicted example, the probe module 14 includes a transducer 20. As used herein, a "transducer" refers to a physical structure of any size and segmentation for converting to and / or from a first energy source (i.e., an electrical energy source, a mechanical energy source, a magnetic energy source, etc.) and ultrasonic energy, wherein the probe module 14 includes a collection of one or more transducers. As described herein, the geometric structure of the collection of transducers may be a linear (one-dimensional) array, an area (two-dimensional) array, or any other suitable geometric structure of any size. At the same time, the imaging and therapeutic transducers described herein may be independent (i.e., separate and independent structures, respectively), partially shared (i.e., partially overlapped between structures for generating therapeutic and imaging ultrasonic energy), or fully shared (i.e., fully overlapped between structures for generating therapeutic and imaging ultrasonic energy). In some contexts, "imaging transducer" or "therapeutic transducer" may be used to refer to a collection of one or more transducers used for associated imaging or therapeutic functions. In other contexts, one may discuss an "imaging beam" or a "therapy beam" generated from a set of one or more transducers, where the sets of transducers used to generate the imaging beam and the therapy beam may be independent, partially shared, or fully shared.

[0038] With this in mind, in the depicted example, the transducer 20 includes both an imaging transducer 22 and a therapeutic transducer 24. In one implementation, the therapeutic transducer 24 may operate at a frequency within 0.2 MHz to 2 MHz (such as 0.5 MHz or 2 MHz). In certain implementations, the probe module 14 and / or the transducer 20 may be selectable or interchangeable to allow the clinician to select an appropriate probe module model or type to best fit the subject or target area background, such as by allowing the clinician to select a probe module 14 and / or transducer 20 with an appropriate nominal depth, axial focus position characteristics, power handling, frequency range, angle adjustment, attenuation adjustment, etc. In addition, in a multi-transducer embodiment, the clinician can customize the probe module 14 by selecting a subset of transducers for activation to enable coherent summing of the therapeutic beam at the target area of ​​the anatomical structure while minimizing interference by obstructing anatomical structures (e.g., ribs, etc.).

[0039] In an alternative embodiment, the transducer 20 may alternatively include a type of transducer capable of operating at both the corresponding imaging frequency and the treatment frequency (e.g., 0.2 MHz to 2 MHz during treatment operation, and 2 MHz to 12 MHz during imaging operation), so that a separate transducer is not provided for each type of corresponding operation. In such embodiments, a single transducer or a single type of transducer may be operated to provide both treatment and imaging type data. This single transducer type approach may be applicable to situations where the target area is shallow and / or high power is not required. In some specific implementations, the probe module 14 and / or the transducer 20 may be selectable or interchangeable to allow the clinician to select an appropriate probe module model or type to best fit the subject or target area background, such as by allowing the clinician to select a probe module 14 and / or transducer 20 with an appropriate nominal depth, axial focus position characteristics, power handling, frequency range, angle adjustment, attenuation adjustment, etc.

[0040] In the depicted example, the probe module 14 includes a microcontroller (MCU) 32 that communicates with a main controller (e.g., a processor) 80 of the treatment module 12; and a field programmable gate array (FPGA) 34 that communicates with the MCU 32 and sensors 40 and / or actuators 50 that may be present and associated with the probe module 14. In this configuration, the MCU 32 and the FPGA 34 can communicate bidirectionally with components of the main controller 80 that coordinate and / or record the operation of various aspects of the probe module 14, or with components directly or indirectly associated with the probe module 14, such as the actuator 50 and / or the sensor 40 (if present). For the sensor 40, various types of sensors may be integrated with the probe module 14, or if they are separate, communicate with the probe module. By way of example, the sensor 40 may include one or more inertial measurement units (IMUs) (which may act as posture sensors), which may include one or more of an accelerometer, a gyroscope, and a magnetometer. As shown in FIG. Figure 1 As shown, one or more sensors 40 (if present) are coupled to the FPGA 34 or otherwise coupled to the hardware controller 98 in a communicative manner. In some embodiments, the main controller 80 may include an alignment controller 30 that determines an alignment score based on the orientation and position of the energy application device and the ability to apply treatment to an anatomical target or region at that orientation and position. In other embodiments, the alignment of the energy application device may be determined via software-implemented functions, firmware-implemented functions, and / or hardware-implemented functions of the alignment controller 30. In addition, the alignment controller 30 may communicate with an automation controller 31 that may automatically adjust the orientation and / or position of the probe 14, the treatment transducer 24, or any other element of the energy application device. It should be understood that although the alignment controller 30 and the automation controller 31 are depicted as being located within the main controller 80, the alignment controller 30 and / or the automation controller 31 may be located at any suitable location within the energy application device (i.e., in some embodiments, they may be implemented as separate controllers and different controllers). In addition, the alignment controller 30 may include any suitable hardware, firmware, and / or software to determine the alignment of the energy application device. One or more controllers depicted within the energy application device (e.g., alignment controller 30, automation controller 31) may be software modules and / or routines executed or implemented by dedicated circuitry on the main controller 80, or may be separated into various hardware blocks (e.g., with additional processing units).

[0041] With respect to the treatment module 12, as previously described, a specific implementation of the treatment module 12 may include a main controller (e.g., a processor) 80, which itself may include or execute various sub-modules or routines, such as may be stored on a memory structure 84. For example, the main controller 80 may include or execute modules or routines that provide functions such as image streaming and remote control, alignment control, artificial intelligence (AI) anatomy recognition and tracking, dose accumulation, user interface, support analysis, system guidance and automation, data logger, etc.

[0042] As with the probe module 14, in certain embodiments, the treatment module 12 may include a hardware controller 86, which may include its own MCU 88 and FPGA 90. Although the probe module 14 and the treatment module 12 are depicted as separate modules for the purposes of illustration and explanation, in practice, the two modules may actually be one and the same module (i.e., an integral structure or device configured to perform the functions of both the treatment module and the probe module as discussed herein). With this in mind, although discussed separately here, in practice, the hardware controllers 86 and 98 may be implemented as a single hardware controller. In the depicted example, the MCU 88 is depicted as communicating with the main controller 80 and its components and modules. The FPGA 90 communicates with and / or controls other components of the treatment module 12, such as a treatment pulse generator-receiver 92 (depicted as communicating with the treatment transducer 24 of the probe module 14), a safety circuit 94, and / or a power management circuit 96. In practice, the main controller 80, in conjunction with the hardware controllers 86, 98, can control the operation of the treatment module 12 and the probe module 14 to perform the application of treatment according to the processes and structures described herein. In some embodiments, the hardware controllers 86, 98 may not include the MCU 88 and / or the FPGA 90. In addition, the system 10 may include a single hardware controller and / or multiple hardware controllers. That is, the various functions corresponding to the various controllers discussed herein may be combined into a single controller, divided between multiple controllers, or otherwise associated with any number of controllers or arrangements of controllers without changing the various functions discussed herein. That is, the present discussion and examples are intended to illustrate and facilitate explanation, but are not intended to limit the functions discussed to the described components or arrangements of components. Further, any programmable logic device and / or processor may be included in the hardware controllers 86, 98 and / or the hardware controllers 86, 98, and as described above, the main controller 80 may be combined into a single main processor device. In addition, as Figure 1As shown in , one or both of the main controller 80 and / or the hardware controller 86 may communicate with one or more memory structures 84 (e.g., volatile or non-volatile memory, firmware configuration, mass data storage device, etc.). As can be appreciated, code or executable routines for performing operations (e.g., treatment procedures or protocols) may be stored on the memory 84 for use by other components. In addition, one or more configurable parameters (such as system settings, imaging device settings, sensor settings or thresholds, etc.) may be stored in the memory structure 84, for example, by a user who has configured or calibrated the system 10 to provide a given subject with a corresponding treatment regimen. In addition, the memory structure 84 can be used to store data (e.g., image data) acquired or generated as part of the treatment procedure, such as for later readout and evaluation.

[0043] In the depicted example, the imaging module 16 is also depicted as a component of the overall system. Such a module, if present, may control or monitor the operation of the transducer 20 (e.g., the imaging transducer 22) to control the generation, collection, and / or processing (e.g., reconstruction) of imaging data. In the depicted example, the imaging module 16 is also shown in communication with the main controller 80 of the treatment module 12, which may control the operation of the imaging module 16 or respond to feedback and data from the imaging module. As with the probe module 14 and the treatment module 12 discussed above, the imaging module 16 is Figure 1 1 and 12 for ease of illustration and explanation of the functional concepts. However, as in the previous examples, the imaging module 16 may actually be the same module as one or both of the probe module 14 and the treatment module 12 (i.e., an integrated structure or device configured to perform the combined functions of the imaging module and one or both of the treatment module and the probe module as discussed herein).

[0044] In view of the foregoing system description and as background, the present technology relates to an image (or unreconstructed image data) guided ultrasound therapy system. In certain embodiments, an alignment controller 30 within the system 10 may provide an alignment relative to a reference. Figure 1 The energy application devices discussed are used in conjunction with aiming and / or alignment aids.

[0045] Various example embodiments of tracking and alignment methods, collectively referred to herein as tracking devices or structures, are described herein. When used, these tracking devices can facilitate the application of safe and effective ultrasound neuromodulation therapy, including in non-clinical settings and / or when operated by untrained users (e.g., the subjects themselves or other individuals who lack clinical or medical training). Therefore, certain embodiments currently described are designed or configured to be easy to use by end users.

[0046] By way of context, there is a high degree of fluctuation in the subject population in conventional ultrasound scanning. Trained sonographers adapt to such fluctuations in subjects by adjusting the placement of the probe on the body, the probe angle, and the system settings to obtain diagnostic images of the target. As mentioned herein, the tracking method of the present invention helps to avoid such manual operation (thereby facilitating placement and use by untrained individuals) to allow personalized, simple tracking and hands-free operation of the subject area of ​​interest during the treatment session. The energy application device can be attached to the subject using a body-worn fixture, or can be freely manipulated around the subject's body. In other embodiments, the energy application device can initially freely manipulate and / or adjust the position and orientation of the device, and can later be fixed using a body-worn fixture.

[0047] As described in the previous section, the energy application device can be automatically and / or manually manipulated to an anatomical target to treat a subject. The treatment module 12 of the system 10 may include an alignment controller 30 that is capable of analyzing a current treatment region of the energy application device (e.g., an area within the ultrasound image data to which the treatment transducer 24 is capable of delivering treatment) based on ultrasound image data of the subject, and evaluating the alignment of the current treatment region of the probe module 14 relative to the anatomical target for treatment of the subject. Based on such evaluation, the delivery of therapeutic ultrasound energy can be automatically and / or manually changed, adjusted, or manipulated to achieve a prescribed treatment outcome. By way of example, when a therapeutic dose is applied, the treatment beam can be electronically and / or manually manipulated to an anatomical target.

[0048] In view of the above, Figure 2 is a schematic diagram of a probe module 14 of a system 10 according to an embodiment of the present disclosure. The probe 14 (e.g., an energy application device) may include one or more transducers 20 (e.g., a therapy transducer 22, an imaging transducer 24) and one or more position sensors 40 (e.g., an inertial measurement unit (IMU) sensor, an optical tracking sensor). The ultrasound probe module 14 may be placed along a subject's body 100 and may include a transducer 20 that generates one or more images of internal tissues of the subject's body 100 corresponding to anatomical targets 104 (e.g., organs, tissues) for treatment. The probe module 14 may be automatically and / or manually manipulated (e.g., in real time) based on image tracking and analysis of the subject's ultrasound image and a determined treatment region 102 (e.g., an area within the ultrasound image data to which the therapy transducer is capable of delivering therapy) relative to a desired anatomical target 104 of the subject via an alignment controller 30.

[0049] Initially, the alignment controller 30 may receive ultrasound image data (e.g., static image data and / or time-series image data corresponding to the breathing cycle of the subject). In addition, the alignment controller 30 may receive additional data including sensor data 40 (e.g., inertial measurement unit (IMU) data, optical tracker data). The image data received by the alignment controller 30 may include two-dimensional planar image data, three-dimensional volumetric image data, A-line image data, Doppler image data, or other ultrasound-based image data. The alignment controller 30 may receive initial subject data (e.g., image data) related to the anatomical target 104 for the therapeutic dose. The data of the initial subject may be determined based on past subject data, population data, etc. The initial subject data may include ultrasound images and / or other image data of the anatomical structure and tissue of the subject, or population-based image data related to the desired anatomical target 104. The initial subject data may include anatomical targets 104 and / or other subject image data identified by the clinician for therapeutic dosing. In addition, the anatomical target 104 may be determined based on an AI model trained using population data, subject-specific data, or both. The AI ​​model may be anatomically specific, and multiple models may correspond to different anatomical regions. A subject-specific AI model may learn an observation trajectory of the subject's anatomical target 104, or utilize a time-series image to feed forward one or more prior detections of the anatomical target 104 as additional input required to locate the anatomical target 104 in the image frame. The AI ​​model may also track overall cumulative and / or average alignment metrics during a dosing session and use these metrics to feed into a continuous learning algorithm that optimizes the device for the subject to maximize the subject's metrics over time.

[0050] The probe module 14 may be moved relative to the subject's body 100, and the alignment controller 30 may receive ultrasound image data via the imaging transducer 24 of the probe module 14. The imaging transducer 24 may generate image data corresponding to the two-dimensional image plane 108, in an unreconstructed form, or in any other suitable image format. The alignment controller 30 may locate the anatomical target 104 within the received ultrasound image data by comparing the image data with previously acquired image data of the anatomical target 104 and / or previously acquired image data of an anatomical region surrounding the anatomical target 104, wherein the previously acquired image data may be subject-specific image data, population-based image data, or both. The alignment controller 30 may use the image data to extract the location of the anatomical target 104 in the ultrasound image data and locate the image data relative to the anatomical target 104. It should be understood that the ultrasound image data received by the alignment controller may completely include, partially include, or exclude the anatomical target 104, so in some embodiments, the alignment controller 30 may not be able to locate the anatomical target 104 in the image data. Alignment controller 30 may also locate a center point within anatomical target 104 and / or a volume of the subject corresponding to anatomical target 104 .

[0051] Based on the received image data, the alignment controller 30 may determine an alignment score (e.g., a percentage alignment score, an average percentage alignment score, a "yes" or "no" indication of alignment) to indicate the degree of alignment and / or whether the treatment region 102 is aligned with the located anatomical target 104. The alignment score may be calculated based on determining the treatment region of the probe module 14 (e.g., the region within the ultrasound image data to which the therapy transducer is capable of delivering therapy) and determining whether the anatomical target 104 is within an appropriate range of the treatment region 102. The alignment score may also be calculated based on whether the anatomical target 104 is within a contour region 110 (e.g., a specific subject region defined by a clinician associated with the location of the anatomical target) to verify the reliability of the alignment and prevent false positive results caused by inaccurate detection of the anatomical target 104 by the alignment controller 30. It should be understood that the alignment controller 30 can be used to calculate the alignment score based on any appropriate criteria based on the received image data, historical subject data, population-based data, and / or a contour region 110 defined by a clinician in the subject image data.

[0052] In some embodiments, as discussed above, the alignment controller 30 may determine an alignment score for each ultrasound image frame (e.g., a time-series image) captured within a certain period of time. In addition, the cumulative alignment score may be determined based on calculating an average and / or weighted average of the alignment scores for each image frame in a set of time-series image data. The cumulative alignment score may be calculated by averaging the alignment scores for each image frame in the image data collected within a certain period of time (e.g., 5 seconds, 10 seconds, or 15 seconds), and / or determining an average alignment score based on one or more alignment scores of image frames collected within a breathing cycle of the subject.

[0053] The alignment controller 30 may analyze the image data (e.g., time-series image data) and determine whether the alignment score of the energy application device is within a predetermined threshold range (e.g., a percentage alignment range) of the anatomical target 104. The alignment score may correspond to an instantaneous score based on the percentage of coincidence of the anatomical target location identified within the image frame data with the treatment region 102 and / or contour region 110 within the image frame, a cumulative score based on the percentage of alignment over time in the image series frame data (e.g., based on each image of alignment / misalignment in each image frame, based on the percentage of coincidence of the anatomical target with the treatment region and / or contour region in each frame), or a combination of both methods. The predetermined threshold range may correspond to a set threshold for an effective therapeutic dosage form based on subject data. For example, an alignment score corresponding to a predetermined threshold range of 90% to 100% alignment may correspond to 5 minutes of therapeutic dosage form application, while the alignment score is within the predetermined threshold range of 90% to 100% alignment; an alignment score corresponding to a predetermined threshold range of 50% to 80% alignment may correspond to 10 minutes of therapeutic dosage form application, while the alignment score is within the predetermined threshold range of 50% to 80% alignment. The therapeutic dosage form time may be dynamically adjusted based on the alignment score threshold range, so that the therapeutic dosage form application time corresponds to the alignment score over time or is otherwise based on the alignment score over time. It should be understood that any suitable therapeutic dosage form time and / or dosing level may be applied to the subject based on the predetermined threshold range of the alignment score. In addition, the predetermined threshold range may be any suitable range based on a fully or partially predicted dose session time, based on a predicted therapeutic efficacy of the alignment score, or both. In some, the alignment controller 30 may determine whether the current alignment score is greater than one or more predicted alignment scores, and send a control signal for the energy application device to maintain the current position and orientation if the current alignment score is greater than one or more predicted alignment scores. This can evaluate the potential position and orientation of the energy application device relative to the current position of the energy application device in terms of dose effectiveness. The predicted alignment score can be calculated based on one or more potential positions and orientations of the energy application device and compared to the alignment score determined for the current position and orientation of the energy application device. If the alignment score for the current position and orientation of the energy application device is greater than one or more predicted alignment scores, the energy application device may maintain the current position and orientation. If the predicted alignment score is higher than the current alignment score, the alignment controller 30 may send a communication to reposition the energy application device to the predicted orientation and position corresponding to the predicted alignment score.The communication may be instructions displayed to the user to move or otherwise adjust the energy application device, control signals for the user to manually adjust the position and orientation, control signals sent to the automation controller 31 to automatically adjust the position or orientation of the energy application device by electronically manipulating and / or actuating one or more therapy transducers 24 and / or probe modules 14 of the energy application device, or a combination of manual and automatic adjustment methods.

[0054] Additionally, the alignment controller 30 can receive the time series image data and can determine whether the anatomical target 104 position in the time series image is aligned with the treatment area 102 of the energy application device to achieve a desired percentage of the target dosage time, thereby ensuring that the entire treatment dose can be delivered within a threshold time limit (e.g., a time limit determined for an effective treatment dosage). The time series data can represent the target path 112 of the anatomical target 104 over time based on the subject's body movement (e.g., breathing cycle).

[0055] Further, the alignment controller 30 may determine an acceptable relative alignment (e.g., as determined by the mechanical and / or electrical steering and / or focusing capabilities of the therapy beam 106 generated by the therapy transducer 22) based on the collected time-series image data and position data and based on the observed trajectory of the anatomical target 104 compared to the treatment area 102. The alignment controller 30 may determine an observed trajectory of the target path 112 of the anatomical target 104 relative to the subject's body 100 over the subject's breathing cycle, and the alignment controller 30 may determine a percentage of the target alignment based on the observed trajectory. In some embodiments, the learned trajectory may be stored in the memory 84 as a subject-specific trajectory and may be used as an input to an algorithm that aligns the anatomical target 104, tracks the anatomical target 104, or both.

[0056] The alignment controller 30 may send a signal to a display and / or electronic device associated with the subject to indicate that the determined target alignment percentage is within a target alignment threshold for an effective therapeutic formulation (e.g., 70% aligned, 80% aligned, 90% aligned). For example, the treatment module 12 may indicate that the treatment beam 106 is properly aligned to obtain an effective therapeutic formulation by displaying a green light or other indication to a user (e.g., a subject and / or a therapist) on a display of the system 10, and the green light may indicate that no adjustment is required. The energy application device may also display a signal indicating an orientation adjustment of the position and / or orientation to improve alignment with the anatomical target 104. The direction signal may include the degree of freedom (DOF) that the treatment transducer 22 should be repositioned. It should be understood that the signal may correspond to any visual prompt, tactile prompt, auditory prompt, or other guidance prompt displayed to the user. The signal may be a control signal that displays an instruction to the user to move the energy application device (or otherwise notifies the user) to allow the user to manually adjust the position and / or orientation, a control signal that sends a control signal to the automation controller 31 to automatically adjust the position and / or orientation of the energy application device by electronically manipulating and / or actuating one or more treatment transducers 24 and / or probe modules 14 of the energy application device, or a combination of manual and automatic adjustment methods.

[0057] The direction signal may also indicate the user's adjustment of the probe module 14 relative to the subject surface 100. The direction signal may include suggested external and / or internal adjustments to maintain the threshold percentage alignment, and may provide multiple guidance prompts to the user throughout the dosing process. For example, the direction signal may be sent to a user device and / or displayed on a display of the system 10, and may indicate to the user to reposition the probe 14 in an upward direction and / or downward direction relative to the subject's body surface 100. The direction signal may be sent from the alignment controller 30, and may indicate to the subject when the directional movement is completed to align the probe module 14 at a determined desired position by the alignment controller 30, thereby maintaining the threshold percentage alignment for effective therapy treatment. Once the alignment of the device within the threshold of the anatomical target 104 is verified via communication with the alignment controller 30, the therapeutic transducer 22 may generate a focused therapeutic beam 106 to provide treatment to the anatomical target 104 of the subject.

[0058] Additionally, in some embodiments, the directional signal from the alignment controller 30 can be sent to the automated controller 31, which can move the probe module 14 without user input to maximize the alignment criteria provided in the directional signal of the alignment controller 30. Further, in some embodiments, the alignment controller 30 can send the directional signal to the automated controller 31 so that adjustments made by the subject and the automated adjustments can be combined to achieve a threshold percentage alignment of an effective therapeutic dosage form. Upon receiving the signal, the automated controller 31 can automatically adjust the position of the probe module 14 on the user, adjust the internal position of the probe transducer 20, or both, to improve alignment with the anatomical target 104. The automated controller 31 can perform internal and / or external adjustments of the probe module 20 until the alignment reaches the target alignment and / or the threshold alignment.

[0059] For example, the alignment controller 30 may determine that the alignment is below a threshold target alignment and may send a signal to the automated controller 31 to adjust the position and / or orientation of the probe module 14 based on the location of the anatomical target 104 within the image data. The alignment controller 30 may dynamically send adjustments to the position and / or orientation to the automated controller 31 to correspond to the patient's breathing cycle, patient movement, etc. This may ensure automatic target alignment of the probe module 14 so that treatment may be effectively applied.

[0060] In some embodiments, the energy application device may include automatic alignment by visual cues and / or signals output via the alignment controller 30, and by the alignment controller 30 sending one or more signals to the automation controller 31 to adjust the position and / or orientation of the probe module 14. For example, the alignment controller 30 may display a red light, play an audible tone, and / or generate a tactile signal to let the user know whether the energy application device has reached a threshold alignment. The alignment controller 30 may also send a signal to the automation controller 31 to automatically adjust the position and / or orientation of the probe module 14 based on the alignment threshold and the received image of the anatomical target 104. Any combination of manual alignment and / or automatic alignment of the probe module 14 may be implemented to effectively apply a therapeutic dose to the patient throughout the treatment session.

[0061] In addition, the alignment controller 30 may receive sensor data as well as image data to determine the observed trajectory and directional motion resulting in a threshold percentage alignment that produces an effective therapeutic dosage form. The sensor data may correspond to or be generated using an inertial measurement unit (IMU) position sensor, which may include one or more of an accelerometer, a gyroscope, and a magnetometer, an optical tracking sensor, or any other suitable sensor. The alignment controller 30 may receive sensor data including data related to the motion of the subject's body surface relative to time (e.g., a breathing cycle) and the position of the probe 14 over time (e.g., a handheld device). It should be understood that the alignment controller 30 may use any suitable position and / or image data to determine a suitable probe 14 position.

[0062] Considering the foregoing, Figure 3 1 is a flow chart of a method 120 of alignment control of an energy application device according to one embodiment of the present disclosure. An alignment controller 30 of the energy application device may receive image frame data generated via an imaging transducer 24 (e.g., an ultrasound transducer), and may determine, based on the received image data, whether an alignment score of the energy application device exceeds a threshold alignment score for effective therapeutic dose application.

[0063] At block 122, alignment controller 30 receives image frame data generated by one or more imaging transducers 24 of the energy application device. The image frame data may include image frames of internal tissue of the subject relative to the position and orientation of the energy application device and the subject's body surface 100. The image frame data may include time-series data of the position of the subject's internal tissue relative to the energy application device over time. The time-series image frame data may be collected over one or more respiratory cycles of the subject or over any other suitable amount of time associated with the motion of the subject's body surface 100.

[0064] At block 124, the alignment controller 30 determines whether the anatomical target 104 is detected within the image data. The alignment controller 30 may determine whether the anatomical target is detected in one or more frames of the image data. As discussed above, the alignment controller 30 may locate the anatomical target 104 within the received ultrasound image data by comparing the image data with previously acquired image data of the anatomical target 104 and / or previously acquired image data of an anatomical region surrounding the anatomical target 104. The alignment controller 30 may utilize the image data to extract the location of the anatomical target 104 in the ultrasound image data and locate the image data relative to the anatomical target 104. If the alignment controller 30 determines that the anatomical target 104 is not detected within the image data, the alignment controller 30 determines at block 126 that the energy application device is not aligned with the anatomical target 104. Based on the anatomical target 104 not being aligned, the alignment controller 30 updates the alignment score at block 128.

[0065] If the anatomical target 104 is detected within the image data, the alignment controller 30 determines at decision block 130 whether the anatomical target 104 is within the treatment region 102 (e.g., an area within the ultrasound image data to which the therapy transducer is capable of delivering therapy). In some embodiments, the alignment controller 30 may determine whether the anatomical target 104 is within the treatment region 104, and additionally, may also determine whether the anatomical target 104 is within the clinician-defined contour region 110. As discussed above, in some embodiments, the contour region 110 (e.g., a clinician-defined subject-specific region associated with the location of the anatomical target) may be implemented in the treatment decision process and used to prevent false positive results based on inaccurate detection of the anatomical target 104 by the alignment controller 30. If the anatomical target 104 is detected to be within the treatment region 102, the alignment controller 30 determines at block 132 that the current image data is aligned, and the alignment controller 30 updates the alignment score associated with the energy application device position and orientation at block 128. If the alignment controller 30 determines at decision block 130 that the detected anatomical target 104 is not within the contour region 110 and the treatment region 102 , the method 120 returns to block 126 and the alignment controller 30 determines that the current image data is not aligned.

[0066] At box 128, the alignment controller 30 updates the alignment score of the energy application device based on whether the current image is aligned. As discussed above, the alignment controller 30 can determine an alignment score (e.g., a percentage alignment score, an average percentage alignment score, a "yes" or "no" indication of alignment) to indicate the degree of alignment and / or whether the treatment area 102 and the located anatomical target 104 are aligned. The alignment score can be calculated based on determining the treatment area of ​​the probe module 14 (e.g., the area within the ultrasound image data to which the treatment transducer is capable of delivering treatment) and determining whether the anatomical target 104 is within the appropriate range of the treatment area 102. The alignment score can also be calculated based on whether the anatomical target 104 is located within the contour area 110 (e.g., a specific subject area defined by a clinician associated with the location of the anatomical target), thereby verifying the reliability of the alignment and preventing false positive results caused by inaccurate detection of the anatomical target 104 by the alignment controller 30. It should be understood that any suitable criteria can be used to calculate an alignment score using the alignment controller 30 based on the received image data and previous subject data and / or clinician-defined contour areas 110 within the subject image data. In some embodiments, the anatomical target 104 can be located in one or more images over time to determine the trajectory of the anatomical target 104. The observed trajectory can be compared to the beam steering capabilities of the energy application device to calculate a predicted cumulative alignment score on the trajectory that can be used. The cumulative alignment score can correspond to one or more breathing cycles of the subject and can be a time-weighted cumulative alignment score. In addition, in some embodiments, a predicted trajectory of the anatomical target 104 can be calculated.

[0067] At decision box 134, the alignment controller 30 determines whether the updated alignment score meets a predetermined threshold range. As discussed above, the predetermined threshold range may correspond to a set threshold for an effective therapeutic dosage form based on the subject data. For example, an alignment score corresponding to a predetermined threshold range of 90% to 100% alignment may correspond to 5 minutes of therapeutic dosage form application, while the alignment score is within the predetermined threshold range of 90% to 100% alignment; an alignment score corresponding to a predetermined threshold range of 50% to 80% alignment may correspond to 10 minutes of therapeutic dosage form application, while the alignment score is within the predetermined threshold range of 50% to 80% alignment. The therapeutic dosage form time may be dynamically adjusted based on the alignment score threshold range, so that the therapeutic dosage form application time corresponds to the alignment score over time or is otherwise based on the alignment score over time. It should be understood that any suitable therapeutic dosage form time and / or dosing level may be applied to the subject based on the predetermined threshold range of the alignment score. In addition, the predetermined threshold range may be any suitable range based on a fully or partially predicted dose session time, based on a predicted therapeutic efficacy of the alignment score, or both. If the alignment controller 30 determines that the updated alignment score is not within the predetermined threshold range, the alignment controller 30 generates a control signal for realignment at box 136. The control signal for realignment may be sent based on the alignment score being outside the predetermined threshold range for more than a certain number of seconds (e.g., 5 seconds, 10 seconds) or a certain number of image frames (e.g., 1, 5, 10). The method 120 may then continue to determine the alignment score, and when the alignment score is within the predetermined threshold range, the energy application device may start or resume tracking and / or dosing.

[0068] The control signal may be sent to an additional controller and / or module within the main controller 80, which may determine the adjustment required to improve the alignment score. The automation controller 31 controller may then send a communication to a user device or interface, which displays instructions on how to adjust the energy application device to improve the alignment score. It should be understood that any suitable control signal may be displayed and / or used to indicate the adjustment of the energy application device. In addition, the control signal may enable the energy application device to be automatically manipulated and / or repositioned to a position more suitable for effective treatment dosing. The control signal may also indicate the adjustment of the position and orientation of the probe module 14 to align with the anatomical predicted trajectory of the target path 112. The control signal may include an adjustment to the position and orientation of the probe module 14, which enables the alignment score to reach, exceed and / or maximize a predetermined threshold range determined for the anatomical target 104. In some embodiments, the trajectory of the target path 112 may be stored in the memory of the system 10 as a subject-specific trajectory.

[0069] If the alignment controller 30 determines that the alignment score does meet the predetermined threshold range, the alignment controller 30 determines whether the user of the energy application is ready to begin dosing at decision block 138. The alignment controller 30 may receive a signal from the user that the user is ready to begin dosing. If the alignment controller 30 receives a signal from the user that the user is ready to begin dosing, the alignment controller may begin the dosing workflow at block 140. Additionally, if a therapeutic dosage form session has already begun, the alignment controller 30 may send a signal to the energy application device to maintain the therapeutic dosage form, and accordingly maintain the position or orientation of the energy application device.

[0070] If the alignment controller 30 does not receive notification that the user is ready to begin dosing, the method 120 returns to block 122 and continues to receive ultrasound image data of the subject's tissue. It should be understood that any suitable method for alignment calculation may be used to calculate the alignment score and the predetermined threshold alignment. It should be understood that the method 120 may be implemented using any of the alignment score determination values ​​described above.

[0071] The method 120 for alignment can be used in conjunction with an application that can help the user guide the alignment via the application's user interface. With this in mind, Figure 4 According to the embodiments of the present disclosure, Figure 1 14. An illustration of a user interface 150 for alignment control of a probe of a neuromodulation delivery system of FIG. 14. During alignment control of an energy application device, a user may be guided by an application including the user interface 150. The user interface 150 may display an ultrasound image generated by the imaging transducer 22 of the probe module 14. The user interface 150 may also display an alignment score visualization 152 that includes a current alignment score of the probe module 14 and also includes a target alignment score metric 154 and an optimal alignment score metric 156.

[0072] At the start of a dosing session, a user may open an application on a user device associated with the energy application device, and the application may display a user interface 150 that displays updated ultrasound image data generated by the imaging transducer 22 of the energy application device. If the alignment controller 30 detects an anatomical target within the image data, the user interface 150 may also display a box outline around the anatomical target 104, and may also display an outline that depicts a clinician-predefined outline area 110 that may additionally be used to determine alignment with the determined location of the anatomical target 104 within the image data. The user interface 150 may be updated over time based on real-time imaging data generated by the imaging transducer 22 and analyzed by the alignment controller 30. The user interface 150 may also display an alignment score visualization 152 that may include a progress bar corresponding to the percent alignment score calculated by the alignment controller 30. The alignment score visualization 152 may also include a target alignment score 154 for a satisfactory dosage form. The target alignment score 154 may be predefined by the application based on the subject data and the population data to treat the condition of the subject. The target alignment score 154 may also be the same as a predetermined threshold for an effective therapeutic dosage form. Additionally, the alignment score visualization 152 may include a marker at an optimal alignment score 156 that is set at the best alignment score achieved in the dosing session.

[0073] Further, the energy application device may guide the user based on the image displayed on the user interface 150 and whether the anatomical target 104 is located within the contour area 110 overlaid on the currently displayed image. The user interface 150 may also provide updates based on control signals generated by the alignment controller 30 to reposition and / or adjust the orientation and / or position of the energy application device based on the determined alignment score.

[0074] Considering the foregoing, Figure 5 1 is a flow chart of a method 160 of delivering a therapeutic dose via a probe module 14 of a neuromodulation delivery system 10 (e.g., system) according to an embodiment of the present disclosure. An alignment controller 30 of an energy application device may receive image frame data generated via an imaging transducer 24 (e.g., an ultrasound transducer), and may determine, based on the received image data, whether a determined alignment score of the energy application device exceeds a threshold alignment for effective therapeutic dose application, and may then initiate dosing and monitor alignment throughout a dosing session.

[0075] At block 162, alignment controller 30 receives image frame data generated by one or more imaging transducers 24 of the energy application device. The image frame data may include image frames of internal tissue of the subject relative to the position and orientation of the energy application device and the subject's body surface 100. The image frame data may include time-series data of the position of the subject's internal tissue relative to the energy application device over time. The time-series image frame data may be collected over one or more respiratory cycles of the subject or over any other suitable amount of time associated with the motion of the subject's body surface 100.

[0076] At decision block 164, the alignment controller 30 determines whether the anatomical target 104 is detected within the image data. The alignment controller 30 may determine whether the anatomical target 104 is detected in one or more frames of the image data. As discussed above, the alignment controller 30 may locate the anatomical target 104 within the received ultrasound image data by comparing the image data to previously acquired image data of the anatomical target 104 and / or previously acquired image data of an anatomical region surrounding the anatomical target 104. The location of the anatomical target 104 may be determined based on subject-specific image data and / or based on population-based image data corresponding to the anatomical region surrounding the anatomical target 104. The alignment controller 30 may utilize the image data to extract the location of the anatomical target 104 in the ultrasound image data and locate the image data relative to the anatomical target 104. If the alignment controller 30 determines that the anatomical target 104 is not detected within the image data, the alignment controller 30 determines at block 168 that the energy application device is not aligned with the anatomical target 104. Based on the anatomical target 104 being misaligned, the alignment controller 30 updates the alignment score at block 170 .

[0077] At box 172, the alignment controller 30 sends a control signal to disable treatment in response to the treatment dose alignment misalignment. At decision box 174, the alignment controller 30 determines whether the alignment score meets one or more realignment criteria. The realignment criteria may include a numerical threshold for the alignment score, a threshold percentage of target alignment over time for the alignment score, or any other suitable numerical and / or time-related alignment criteria. For example, if the alignment score is 20% below a predetermined alignment score threshold, the realignment criteria may be met and the alignment controller 30 may send a signal to trigger realignment. In another example, if the alignment score is determined to be less than a predetermined threshold range for more than 5 consecutive seconds, the alignment controller 30 may send a signal to trigger realignment.

[0078] For example, the alignment score during the session may still be above a predetermined threshold range, and the dosing session may continue. If the alignment score does not meet the realignment criteria, the method 160 returns to block 162 and receives current image data. If the alignment score meets the realignment criteria, the alignment controller 30 may return to the alignment workflow at block 176.

[0079] Returning to block 164, if the anatomical target 104 is detected within the image data, the alignment controller 30 determines at decision block 178 whether the anatomical target 104 is located within the treatment region 102 (e.g., an area within the ultrasound image data to which the therapy transducer is capable of delivering therapy). As discussed above, the contour region 110 (e.g., a clinician-defined subject-specific region associated with the location of the anatomical target) may also be used in conjunction with the treatment region 102 to verify the reliability of the alignment and prevent false positive results based on inaccurate detection of the anatomical target 104 by the alignment controller 30. If the anatomical target 104 is detected to be within the contour region 110 and / or the treatment region 102, the alignment controller 30 determines at block 180 that the current image data is aligned, and the alignment controller 30 updates the alignment score associated with the energy application device position and orientation at block 182. If the alignment controller 30 determines at decision block 178 that the detected anatomical target 104 is not within the contour region 110 and / or the treatment region 102 , the method 120 returns to block 168 and the alignment controller 30 determines that the current image data is not aligned.

[0080] At box 182, the alignment controller 30 updates the alignment score of the energy application device based on the image alignment. As discussed above, the alignment controller 30 may determine an alignment score (e.g., a percentage alignment score, an average percentage alignment score, a "yes" or "no" indication of alignment) to indicate the degree of alignment and / or whether the treatment area 102 is aligned with the located anatomical target 104. In addition, the alignment score may correspond to one or more alignment criteria, which may include one or more alignment scores associated with a threshold alignment score for a yes and / or no indication of alignment. The alignment criteria may also correspond to a combination of an alignment score and one or more checklist items associated with probe alignment. The checklist may be used as an alignment criterion in conjunction with the alignment score to determine a yes and / or no indication of alignment.

[0081] The alignment score may be calculated based on determining the treatment region of the probe module 14 (e.g., the region within the ultrasound image data to which the therapy transducer is capable of delivering therapy) and determining whether the anatomical target 104 is within an appropriate range of the treatment region 102. The alignment score may also be calculated based on whether the anatomical target 104 is within the contour region 110 and the treatment region 102 (e.g., a clinician-defined specific subject region associated with the location of the anatomical target), thereby verifying the reliability of the alignment and preventing false positive results due to inaccurate detection of the anatomical target 104 by the alignment controller 30. It should be understood that any suitable criteria can be used to calculate the alignment score using the alignment controller 30 based on the received image data and previous subject data and / or the clinician-defined contour region 110 within the subject image data.

[0082] At box 184, the alignment controller 30 is capable of delivering a dose to the anatomical target 104. The dose may be delivered based on the alignment score and the predetermined threshold range corresponding to the alignment score. For example, the predetermined threshold range may correspond to a set threshold for an effective therapeutic dosage form based on subject data. For example, an alignment score corresponding to a predetermined threshold range of 90% to 100% alignment may correspond to a 5-minute therapeutic dosage form application, and an alignment score corresponding to a predetermined threshold range of 50% to 80% alignment may correspond to a 10-minute therapeutic dosage form application. It should be understood that any suitable therapeutic dosage form time and / or dosing level may be applied to the subject based on a predetermined threshold range of the alignment score. In addition, the predetermined threshold range may be any suitable range based on a fully or partially predicted dose session time, a predicted therapeutic efficacy based on the alignment score, or both. In some embodiments, the dosing controller may receive information from the alignment controller 30, the information including the determined position of the anatomical region 104, the alignment score, the predetermined threshold range, and the control signal. When the control signal indicates that the anatomical target 104 is aligned and / or the alignment score is within a predetermined threshold range, the dosing controller may send a signal to cause the treatment transducer 24 to begin dosing. The cycle time of locating the anatomical target 104 within the image frame, determining the control signal, and activating the treatment beam to direct the treatment toward the located anatomical target 104 may be less than 500 milliseconds or any other suitable cycle time. In some embodiments, the dosing controller may accumulate a measured or estimated value of the total dose applied to the anatomical target 104 (e.g., number of pulses, dosing time, accumulated dosing energy). The dosing controller may send a signal when the cumulative dosed amount reaches a threshold amount of the dose required for the therapeutic effect. In certain embodiments, the dosing controller may be housed in the main controller 80 of the energy application device.

[0083] At decision block 186, the alignment controller 30 determines whether the desired dosage has been completed. If the alignment controller 30 determines that the desired dosage form has not been delivered, the method 160 returns to block 162. If the alignment controller 30 determines that the desired dosage has been delivered, the alignment controller 30 determines at block 190 that the dosing session is complete and may send a signal to the user device to indicate that dosing is complete.

[0084] Throughout the dosing session, the user may be guided by an application on the user device and / or the display of the energy application device. Figure 6 1 is an illustration of a dosing user interface 200 for dosing a therapy via a probe of a neuromodulation delivery system 10 according to an embodiment of the present disclosure. During dosing using an energy application device, a user may be guided by an application including the dosing user interface 200. The dosing user interface 200 may display an ultrasound image generated by the imaging transducer 22 of the probe module 14. The dosing user interface 200 may also display an alignment score visualization 152 that includes a current alignment score for the probe module 14 and also includes a target alignment score metric 154 and an optimal alignment score metric 156. Additionally, the dosing user interface 200 may display a progress visualization 202 corresponding to the progress of the dosing throughout the dosing session, as well as a display of an estimated remaining dosing time 206 and an elapsed time 204.

[0085] At the start of a dosing session, a user may open an application on a user device associated with the energy application device, and the application may display a dosing user interface 200 that displays updated ultrasound image data generated by the imaging transducer 22 of the energy application device. If the alignment controller 30 detects an anatomical target within the image data, the dosing user interface 200 may also display a box around the anatomical target 104, and may also display an outline indicating an outline area 110 predefined by the clinician, which may additionally be used to determine alignment with the determined location of the anatomical target 104 within the image data. The dosing user interface 200 may be updated over time based on real-time imaging data generated by the imaging transducer 22 and analyzed by the alignment controller 30. The dosing user interface 200 may also display an alignment score visualization 152 that may include a progress bar corresponding to the percentage alignment score calculated by the alignment controller 30. The alignment score visualization 152 may also include a target alignment score 154 for a satisfactory dosage form. The target alignment score 154 may be predefined by the application based on the subject data and the population data to treat the condition of the subject. In addition, the alignment score visualization 152 may include a marker for the best alignment score 156, which is set at the best alignment score achieved during the dosing process. The progress visualization 202 may correspond to the dosing progress throughout the session based on the alignment score and the predefined dosage form time based on the predetermined threshold alignment corresponding to the dosing progress throughout the session. The dosing progress throughout the session may correspond to a number of pulses or total dosage time until the target number of pulses or dosage time is accumulated.

[0086] Further, the energy application device can guide the user based on the image displayed on the user interface 150 and whether the anatomical target 104 is located within the outline area 110 overlaid on the currently displayed image. The user interface 150 can also provide updates based on the control signal generated by the alignment controller 30 to reposition and / or adjust the orientation and / or position of the energy application device based on the determined alignment score. The dosing user interface 200 can also display the time remaining in the dosing session 206.

[0087] In view of the above, Figure 7 is a schematic diagram of tracking over time using a therapy transducer 22 with adjustable focus in one dimension according to an embodiment of the present disclosure. The energy application device can adjust the focus of the therapy transducer 22 over time based on the position of the anatomical target 104 within the image frame generated by the imaging transducer 24. The alignment controller 30 can determine the focus of the therapy transducer 22 for the therapy beam 106 to provide effective treatment to the anatomical target 104 during the treatment session.

[0088] In some embodiments, the therapy transducer 22 can be capable of one-dimensional tracking of the anatomical target 104. For example, the therapy transducer 22 can be pointed in a fixed direction and can have the ability to adjust the focus in one dimension. The focus adjustment can correspond to depth and can be adjusted via electronic focus control, and the therapy beam 106 can be adjusted through the x-axis, y-axis, and angle adjustment axes. The focus of the therapy transducer 22 can also be adjusted via mechanical control.

[0089] The alignment controller 30 can detect when the anatomical target 104 is within the focus range of the therapy transducer 22 and when the therapy beam 106 is aligned with the nominal direction of the anatomical target 104. The system 10 can configure the depth of the therapy transducer 22 and can apply therapy when the anatomical target 104 is within the control range of the therapy transducer 22. The system 10 can not apply therapy or stop applying therapy when alignment with the anatomical target 104 is lost, and can resume applying therapy when alignment at a later point is within the range of the therapy transducer 22.

[0090] For example, at an initial time 210, the alignment controller 30 may determine based on the imaging transducer data 24 that the anatomical target 104 may not be within the focus range of the therapy transducer 22, and the system 10 may not apply therapy. At a second time 212, the alignment controller 30 may detect that the anatomical target 104 is within the focus range of the therapy transducer 22, but needs to be focused to a greater depth. The alignment controller 30 may send a signal to the therapy transducer 22 to increase the depth of the therapy beam 106, and may send a signal to the system 10 to apply therapy so that therapy may be applied to the anatomical target 104 via the therapy transducer 22. At a third time 214, the alignment controller 30 may determine that the anatomical target 104 is within the focus range of the therapy transducer 22, but the depth of the therapy beam 106 may need to be reduced. The alignment controller 30 may then send a signal to the therapy transducer 22 to reduce the depth of the therapy beam 106, and the system 10 may continue to apply therapy. At a fourth time 216, the alignment controller 30 may determine, based on the generated image data, that the depth of the therapy beam 106 must be further reduced to correspond to the current position of the anatomical target 104. The alignment controller 30 may send a signal to the therapy transducer 22 to reduce the depth of the therapy beam 106, and the system 10 will continue to apply therapy. At a fifth time 218, the alignment controller 30 may determine that the anatomical target 104 is not within the focus range of the therapy transducer 22, and may send a control signal to the system 10 to stop the application of therapy. It should be understood that the therapy transducer 22 may adjust the focus in one dimension relative to the detected position of the anatomical target 104.

[0091] In some embodiments, during dosing, the alignment controller 30 may send a signal to cycle the adjustment mode relative to the subject's breathing cycle, and / or may send an updated signal based on the detected subject's breathing cycle throughout the treatment dosing session. The probe module 14 may include one or more IMU sensors that collect IMU data of the subject over time during the dosing session. The IMU sensor may include one or more of an accelerometer, a gyroscope, and a magnetometer, or any combination of suitable sensor types. The IMU data can be used to track the movement of the anatomical target 104 in the subject's body throughout the subject's breathing cycle. The alignment controller 30 can receive the IMU data and determine changes in the position and orientation of the probe module 14 relative to the subject's breathing cycle to provide target dosing throughout the subject's breathing cycle.

[0092] In view of the above, Figure 8 2 is a graphical representation of the correlation of observed motion of the portal vein within an ultrasound image plane with motion of an energy application device based on IMU sensor data according to an embodiment of the present disclosure 220. IMU data 224 may be acquired using a probe module 14 (e.g., attached to an IMU) held on a subject's body surface 100. The probe module 14 may implement a synchronization sequence consisting of rocking the probe module 14 one or more times during the synchronization sequence while the subject completes one or more breathing cycles.

[0093] The graph displays time in seconds on the x-axis and normalized amplitude relative to sensor data on the y-axis. The graph depicts the normalized amplitude of portal vein motion 222 in ultrasound image data over time, and IMU sensor data 224 representing the movement of the probe module 14 over time. The graph depicts a synchronization sequence, a normal breathing cycle of five breaths, and an additional synchronization sequence. The IMU sensor data is compared to the accelerometer output for the probe module 14. The motion of the portal vein 222 is calculated as the pixel distance from the center of the annotated anatomical region 104 for each image frame to the center of the annotated anatomical region 104 on the first frame received. The portal vein motion data 222 and the IMU sensor motion data 224 are time adjusted, cross-correlated to align, remove direct current (DC) offset, and normalized in the displayed graph.

[0094] The figure illustrates the internal anatomical target motion and predicted path of anatomical target 104 using an IMU sensor to track during the subject's respiration. It should be understood that various embodiments may be implemented based on multiple data fusion algorithms, reduced image complexity based sensor tracking, or any other suitable tracking method for monitoring the motion of anatomical target 104 during the subject's respiration. In some embodiments, IMU position sensor 40 may help detect the motion of anatomical target 104 and / or detect the subject's breathing cycle.

[0095] In view of the above, Fig. 9A 1 is a schematic diagram of tracking over time using a fixed two-dimensional imaging transducer 24 and a mechanically oscillating therapy transducer 22 with external motion adjustment according to an embodiment of the present disclosure. In some embodiments, the therapy transducer 22 can be mechanically oscillated (e.g., pivoted in an azimuth plane) via motor control and include axial electronic focusing of the therapy transducer 22. The alignment controller 30 can track the anatomical target 104 within the image plane 108. In addition, the alignment controller 30 can determine when the anatomical target 104 is within the treatment region 102 of the therapy transducer 22 (e.g., the region about which the therapy transducer can pivot to apply therapy). The alignment controller 30 can then send a signal to the therapy probe module 14 to mechanically swing toward the anatomical target 104, and / or can send a signal to electronically adjust the depth of the therapy beam 106 to focus the therapy beam 106 at the depth of the anatomical target 104. The therapy transducer 22 may be located external to the lens 101 of the energy application device, and the therapy transducer 22 may pivot using external motion relative to the lens 101. It should be appreciated that the therapy transducer 22 may adjust focus in one dimension relative to the detected location of the anatomical target 104. The alignment controller 30 may send a signal to cycle this adjustment pattern relative to the subject's breathing cycle, and / or may send updated signals throughout the therapy dosing session.

[0096] For example, at an initial time 230, the alignment controller 30 may determine, based on the imaging transducer data 24, that the anatomical target 104 may not be within the treatment region 102 of the therapy transducer 22, and that the system 10 may not apply therapy. The alignment controller 30 may detect at a second time 232 that the anatomical target 104 is within the treatment region 102 of the therapy transducer 22, but adjustment requires that therapy be applied to the anatomical target 104 by pivoting the probe module 14 to the left in the azimuth plane and increasing the depth of the therapy beam 106 using axial electronic focusing. The alignment controller 30 may send a signal to the probe module 14 (e.g., using an actuator within the probe module 14) to pivot to the left and increase the depth of focus, and may send a signal to the system 10 to apply therapy, so that therapy may be applied to the anatomical target 104. At a third time 234, the alignment controller 30 may determine that the anatomical target 104 is within the treatment region 102 of the therapy transducer 22, but adjustment is required to focus the therapy beam 106 by sending a signal to the probe module 14 to pivot right in the azimuth plane to apply therapy to the anatomical target 104. The alignment controller 30 may then send a signal to the probe module 14 to pivot right, and the system 10 will continue therapy. At a fourth time 236, the alignment controller 30 may determine based on the generated image data that the depth at which the therapy beam 106 is focused may need to be further reduced to correspond to the anatomical target 104, and that the probe module 14 may need to pivot right. The alignment controller 30 may send a signal to the therapy transducer 22 to reduce the depth of the therapy beam 106 and cause the probe module 14 to pivot right and the system 10 to maintain therapy application. At a fifth time 238, the alignment controller 30 may determine that the anatomical target 104 is not within the treatment area 102 of the treatment transducer 22, and may send a control signal to the system 10 to stop applying treatment. It should be understood that the treatment transducer 22 may adjust the focus relative to the detected position of the anatomical target 104. The alignment controller 30 may send a signal to cycle the adjustment mode relative to the breathing cycle of the subject, and / or may send an updated signal throughout the treatment dosing session. That is, the alignment controller 30 may send a signal to continuously apply the therapeutic dosage form throughout the treatment session when the alignment score reaches the threshold alignment score. It should be understood that the alignment controller 30 may provide any suitable signal (e.g., "aligned", "misaligned", "tending towards alignment", "tending away from alignment", "in place but not properly oriented", etc.) based on the determined alignment of the energy application device. That is, the signal may be a signal to maintain the position and / or orientation of the energy application device, maintain the therapeutic dosage form, stop the therapeutic dosage form, and / or adjust the position and / or orientation of the energy application device.

[0097] In view of the above, Fig. 9B1 is a schematic diagram of tracking control over time using a fixed two-dimensional imaging transducer 24 and a mechanically oscillating therapy transducer 22 with internal motion adjustment according to one embodiment of the present disclosure. In some embodiments, the therapy transducer 22 can be mechanically oscillated (e.g., pivoted in an azimuth plane) via motor control and include axial electronic focusing of the therapy transducer 22. The alignment controller 30 can track the anatomical target 104 within the image plane 108. In addition, the alignment controller 30 can determine when the anatomical target 104 is within the treatment region 102 of the therapy transducer 22. The alignment controller 30 can then send a signal to the probe module 14 (e.g., an actuator located within the probe module 14) to mechanically oscillate toward the anatomical target 104, and / or can send a signal to electronically adjust the depth of the therapy beam 106 to focus the therapy beam 106 at the depth of the anatomical target 104. The therapy transducer 22 may be located internally of the lens 101 of the energy application device, and the therapy transducer 22 may pivot using internal motion relative to the lens 101. It should be appreciated that the therapy transducer 22 may adjust focus in one dimension relative to the detected location of the anatomical target 104. The alignment controller 30 may send a signal to cycle this adjustment pattern relative to the breathing cycle of the subject, and / or may send updated signals throughout the therapy dosing session.

[0098] As discussed above, the probe module 14 can be automatically and / or mechanically steered or focused over time based on the position of the anatomical target 104 relative to the therapeutic transducer. In a similar manner, the therapeutic transducer 24 can be mechanically swung and / or focused over time 240, 242, 244, 246, 248 using internal motion to achieve alignment with the anatomical target 104.

[0099] In view of the above, Fig. 10A is a schematic diagram of tracking over time using a two-dimensional imaging transducer 24 coupled to a therapeutic transducer 22 with external motion adjustment according to one embodiment of the present disclosure. The energy application device may include a two-dimensional imaging transducer 24 and a therapeutic transducer 22, both of which are fixed relative to each other and mechanically swung via motor control and electronically focused relative to tracking of an anatomical target 104 of a subject. The system 10 may swung the transducer assembly 22, 24 including the imaging transducer 24 and the therapeutic transducer 22 to maintain alignment of the anatomical target 104 throughout the dosing process. The method of motion of the transducer assembly 22, 24 may be located external to the lens 101 of the energy application device. It should be understood that the transducer assembly 22, 24 may adjust the focus relative to the detected position of the anatomical target 104. The alignment controller 30 may send a signal to cycle the adjustment pattern relative to the breathing cycle of the subject, and / or may send an updated signal throughout the therapeutic dosing session.

[0100] For example, at the initial time 250, the alignment controller 30 may determine, based on the imaging transducer data 24, that the anatomical target 104 may not be within the treatment region 102 of the treatment transducer 22, and the system 10 may stop applying treatment. The alignment controller 30 may detect at the second time 252 that the anatomical target 104 is within the treatment region 102 of the treatment transducer 22, but to maintain focus, send a signal to the probe module 14 to pivot left in the azimuth plane and increase the depth of the treatment beam 106 through axial electronic focusing, thereby treating the anatomical target 104. The alignment controller 30 may send a signal to the probe module 14 to pivot left and increase the depth of focus, and may send a signal to the system 10 to apply treatment, so that treatment may be applied to the anatomical target 104. At a third time 254, the alignment controller 30 may determine that the anatomical target 104 is within the treatment region 102 of the therapy transducer 22, and in order to focus the transducer assembly 22, 24, the assembly is pivoted to the right in the azimuth plane to apply therapy to the anatomical target 104. The alignment controller 30 may then send a signal to the probe module 14 to pivot to the right, and the system 10 may continue to apply therapy. At a fourth time 256, the alignment controller 30 may determine based on the generated image data that the depth of the therapy beam 106 must be further reduced to correspond to the location of the anatomical target 104, and the transducer assembly 22, 24 may be pivoted to the right. The alignment controller 30 may send a signal to the probe module 14 to reduce the depth of the therapy beam 106 and pivot to the right, and the system 10 may continue to apply therapy. At a fifth time 258, the alignment controller 30 may determine that the anatomical target 104 is not within the treatment region 102 of the therapy transducer 22, and may send a control signal to the system 10 to stop applying therapy. It should be appreciated that transducer assemblies 22, 24 may adjust focus relative to the detected location of anatomical target 104. Alignment controller 30 may send signals to cycle this adjustment pattern relative to the subject's breathing cycle, and / or may send updated signals throughout a therapy dosing session.

[0101] Fig. 10Bis a schematic diagram of tracking over time using a two-dimensional imaging transducer 24 coupled to a therapeutic transducer 22 with internal motion regulation according to one embodiment of the present disclosure. The energy application device may include a two-dimensional imaging transducer 24 and a therapeutic transducer 22, both of which are fixed relative to each other and mechanically swung via motor control and electronically focused relative to tracking of an anatomical target 104 of a subject. The system 10 may sway the transducer assembly 22, 24 including the imaging transducer 24 and the therapeutic transducer 22 to keep the anatomical target 104 aligned in a fixed direction. The motion method of the transducer assembly 22, 24 may be located inside the lens 101 of the energy application device. As discussed above, the therapeutic transducer may be automatically and / or mechanically steered or focused over time based on the position of the anatomical target 104 relative to the transducer assembly 22, 24. In a similar manner, the transducer assemblies 22 , 24 may be mechanically rocked and / or focused over time 260 , 262 , 264 , 266 , 268 using internal motion to achieve alignment with the anatomical target 104 .

[0102] In view of the above, Fig.11 is a schematic diagram of time-lapse tracking of imaging and therapy using a single linear transducer 200 according to one embodiment of the present disclosure. The energy application device may include an imaging transducer 22 and a therapy transducer 24 combined in a single component (e.g., a linear transducer assembly) 200. In other embodiments, the imaging transducer 22 and the therapy transducer 24 comprising the linear transducer assembly 200 are the same transducer. The liner transducer assembly 200 may include electronically steered beams in an azimuthal plane for both the imaging element and the therapy element of the linear imaging transducer 200. The illustration depicts interleaved imaging and therapy via a single linear transducer 200.

[0103] For example, at an initial time 270, an imaging frame 108 based on the imaging transducer 22 is shown at the initial time. The alignment controller 30 may detect at a second time 272 that the linear transducer beam is within the treatment range of the anatomical target 104 based on the imaging frame 108 at the time 270, and send a signal to electronically steer the beam to the left in the azimuth plane and increase the depth of the treatment beam 106 through axial electronic focusing to treat the anatomical target 104. In some embodiments, the personalized contour 110 region affects the treatment formulation such that when the location of the anatomical target 104 is detected outside the contour region 110, no treatment is applied. In these embodiments, when the location of the region of interest is additionally located within the contour region 110, the treatment beam 106 may be focused and directed to the location of the anatomical target 104.

[0104] Additionally, the alignment controller 30 may send a signal to the linear transducer assembly 200 to steer left and increase the depth of focus, and may send a signal to the system 10 to apply therapy, so that therapy may be applied to the anatomical target 104. At a third time 274, the imaging frame 108 may depict that the anatomical target 104 is within the treatment region 102. At a fourth time 276, the alignment controller 30 may send a signal to focus the linear transducer assembly 200 by electronically steering right in the azimuth plane, so that therapy may be applied to the anatomical target 104. The alignment controller 30 may then send a signal to the linear transducer assembly 200 to steer right, and may send a signal to the system 10 to apply therapy. At a fifth time 278, the alignment controller 30 may receive an imaging frame 108 indicating that the anatomical target 104 is within the treatment region 102. At a sixth time 280, the alignment controller 30 may send a signal to the linear transducer assembly 200 to reduce the depth of the treatment beam 106 and to electronically steer to the right, and the system 10 will continue to apply treatment. At a seventh time 282, the alignment controller 30 may determine that the anatomical target 104 is not located within the treatment area based on the imaging frame data. It should be understood that the linear transducer assembly 200 may adjust the focus relative to the detected location of the anatomical target 104. The alignment controller 30 may send a signal to cycle this adjustment pattern relative to the subject's breathing cycle, and / or may send updated signals throughout the treatment dosing session.

[0105] In view of the above, Fig. 12A is a schematic diagram of a three-dimensional trace with motion depicted about an azimuth axis, and Fig. 12B is a three-dimensional tracking with movement depicted around an elevation axis according to one embodiment of the present disclosure. Fig. 12A and Fig. 12B Together, the alignment and tracking of the three-dimensional target path 106 over time by adjusting the energy application device in both the azimuth and elevation axes are shown. In three-dimensional tracking, the entire probe module 14 can remain fixed to the subject's body surface 100 by internal rotation of the treatment transducer 220 about the elevation and azimuth axes; or, the probe module 14 can be moved relative to the subject's body surface 100 by a gimbal-based (or any other mechanical configuration or linkage) mechanism for externally rotating the treatment transducer 220 about the elevation and azimuth axes. The elevation and azimuth axis rotations are adjusted internally or externally to align and track the anatomical target 104 along the three-dimensional target path 106. In addition, in some embodiments, the treatment transducer 220 can have two-dimensional electronic steering and focusing capabilities about the azimuth axis.

[0106] Adjustments about the azimuth and elevation axes may include electronically controlling the array of therapy transducers 220 and repositioning the therapy transducers 220 based on the position of the anatomical target 104 relative to the energy application device over time using motors internal or external to the system 10. For example, at an initial time 300, the alignment controller 30 may detect based on the imaging data that the anatomical target 104 may not be located within the treatment region 102 of the therapy transducer 220. The alignment controller 30 may detect at a second time 302 that the anatomical target 104 is within the treatment range 102 of the therapy transducer 220, and may send a control signal via motor control to rotate the therapy transducer 220 to the left along the azimuth axis to align with the detected target location 104, and may send a control signal to the system 10 to apply therapy. At a third time 304 , alignment controller 30 may send control signals to rotate therapy transducer 220 right along the azimuth axis and right along the elevation axis via motor control and continue to power on system 10 to provide therapy to anatomical target 104 .

[0107] Further, the gimbal assembly may include imaging in two-dimensional focus with electronic therapy that can adjust the beam focus in two dimensions by slight external tilting motion of the entire probe assembly that follows a signal corresponding to the movement of the subject's body 100 during respiration. In another embodiment, the gimbal assembly may include a swash plate concept drive system that includes a main rotor shaft that enables the sensor to rock in the azimuth plane, and a swash plate with a control rod that can control the tilt and rotation of the sensor 220. In another embodiment, the gimbal may include a parallel mechanism with a ball and universal joint that can move the therapy transducer. It should be understood that any tracking method can be applied to track the subject's anatomical target 104 over time.

[0108] In view of the above, Fig.13 1 is an illustration of a view of the transducer 20 relative to the subject's body surface 100. The transducer 20 may include a two-dimensional imaging array 22 and a two-dimensional treatment array 24. In this embodiment, the two-dimensional imaging array 22 and the two-dimensional treatment array 24 can be steered and / or focused in three dimensions. Specifically, when three-dimensional focusing and steering are used, the image plane is an image volume and the treatment area 102 is a three-dimensional treatment area. Therefore, the target path 112 can be represented in three-dimensional space and the contour area 110 can be represented as a volume. This can enable the treatment beam 106 to be guided and / or focused in three dimensions relative to the treatment area 102 and the contour volume.

[0109] In view of the above, Fig.14is a schematic diagram of a fixed arrangement of an imaging transducer 22 and a therapeutic transducer 24 according to an embodiment of the present disclosure, which can be imaged in a two-dimensional plane and manipulated and / or focused within the two-dimensional plane. The energy application device may include a fixed arrangement of a therapeutic transducer 22, an imaging transducer 24, and one or more position sensors 40 (e.g., an inertial measurement unit (IMU) sensor, an optical tracking sensor). The transducer 20 can be automatically manipulated and / or manually manipulated (e.g., in real time) based on image tracking and analysis of an ultrasound image of the subject and a determined treatment area (e.g., an area within the ultrasound image data to which the therapeutic transducer can deliver therapy) relative to a desired anatomical target 104 of the subject. In some embodiments, two or more planar arrays in a single unit can be mechanically manipulated to increase the therapeutic range of the energy application device. This can help keep the anatomical target 104 within the treatment area 102 of the therapeutic transducer 24, and / or center the anatomical target 104 within the range of the energy application device to provide effective treatment.

[0110] Initially, the alignment controller 30 may receive ultrasound image data (e.g., static image data and / or time-series image data corresponding to the breathing cycle of the subject). In addition, the alignment controller 30 may receive additional data including sensor data 40 (e.g., inertial measurement unit (IMU) data, optical tracker data). The image data received by the alignment controller 30 may include two-dimensional planar image data from the fixed imaging transducer 22. The imaging transducer may be located at the center of the probe module 14 and may be connected to two therapeutic transducers 24 located at either end of the imaging transducer 22.

[0111] The imaging transducer 24 may generate image data corresponding to the two-dimensional image plane 108. The alignment controller 30 may locate the anatomical target 104 within the received ultrasound image data by comparing the image data with previously acquired image data of the anatomical target 104 and / or previously acquired image data of an anatomical region surrounding the anatomical target 104. The alignment controller 30 may utilize the image data to extract the location of the anatomical target 104 in the ultrasound image data and locate the image data relative to the anatomical target 104. It should be understood that the ultrasound image data received by the alignment controller may completely include, partially include, or exclude the anatomical target 104, and thus, in some embodiments, the alignment controller 30 may be unable to locate the anatomical target 104 in the image data. The alignment controller 30 may also locate a center point within the anatomical target 104 and / or a volume of the subject corresponding to the anatomical target 104.

[0112] Based on the received image data, the alignment controller 30 may determine an alignment score (e.g., a percentage alignment score, an average percentage alignment score, a "yes" or "no" indication of alignment) to indicate the degree of alignment and / or whether the treatment region 102 and the located anatomical target 104 are aligned. The alignment score may be calculated based on determining the treatment region of the probe module 14 (e.g., the region within the ultrasound image data to which the therapy transducer is capable of delivering therapy) and determining whether the anatomical target 104 is within an appropriate range of the treatment region 102. The alignment score may also be calculated based on whether the anatomical target 104 is within a contour region 110 (e.g., a specific subject region defined by a clinician associated with the location of the anatomical target) to verify the reliability of the alignment and prevent false positive results caused by inaccurate detection of the anatomical target 104 by the alignment controller 30. It should be understood that any suitable criteria can be used to calculate the alignment score using the alignment controller 30 based on the received image data and previous subject data and / or the clinician-defined contour region 110 within the subject image data. It should be appreciated that two-dimensional tracking does not require external or internal motion, and the geometry and / or frequency range of each therapy transducer 24 and / or imaging transducer 22 may be optimized for the appropriate imaging and / or therapy needs of the subject.

[0113] This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any included methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to fall within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insignificant differences from the literal language of the claims.

Claims

1. A neuromodulatory delivery system, comprising: Energy application equipment; and An alignment controller, wherein the alignment controller is configured to perform actions comprising: receiving image data from the energy application device, wherein the image data includes an image of internal tissue based on a current position and orientation of the energy application device relative to a subject; determining an alignment score of the energy application device relative to an anatomical target based on the image data; A control signal is provided to maintain or change one or both of the current position or orientation of the energy application apparatus in response to the alignment score.

2. A neuromodulation delivery system according to claim 1, wherein the energy application device comprises one or more ultrasound imaging transducers and one or more therapeutic transducers disposed within a housing of the energy application device.

3. A neuromodulation delivery system according to claim 2, wherein the position of the energy application device includes an external position of the energy application device relative to the subject, an imaging transducer, a therapeutic transducer, or a position of both the imaging transducer and the therapeutic transducer within the energy application device.

4. A neuromodulation delivery system according to claim 1, wherein the anatomical target is extracted from the image data by positioning the image data relative to the anatomical target, wherein the image data completely, partially or excludes the anatomical target.

5. The neuromodulation delivery system of claim 4, wherein locating the image data comprises comparing the image data to subject-specific data, population-specific data, or both the subject-specific data and the population-specific data.

6. The neuromodulation delivery system of claim 1, wherein the alignment score comprises a cumulative percentage alignment score comprising an average of a plurality of alignment scores over time.

7. A neuromodulation delivery system according to claim 1, wherein determining the alignment score includes determining that the anatomical target detected in the image frame is located within a treatment area, wherein the treatment area includes a range within which the neuromodulation delivery system is capable of delivering treatment to the anatomical target.

8. A neuromodulation delivery system according to claim 1, wherein the energy application device includes a position sensor configured to generate position data over time and configured to track the position of the energy application device relative to the anatomical target during the subject's breathing cycle.

9. A neuromodulation delivery system according to claim 1, wherein the control signal is sent to an automated controller located within the energy application device, wherein the automated controller electronically adjusts the position, orientation, or both the position and orientation of the energy application device in response to the control signal.

10. The neuromodulation delivery system of claim 1, wherein the control signal comprises a direction signal indicating a direction to move or orient the energy application device to satisfy a threshold range.

11. The neuromodulation delivery system of claim 10, wherein the directional signal comprises depth of field (DOF) data and indicates directional movement within a two-dimensional plane relative to the subject.

12. The neuromodulation delivery system of claim 1, wherein the image data comprises two-dimensional planar data, three-dimensional volumetric data, Doppler data, or any combination thereof.

13. The neuromodulation delivery system of claim 1, wherein the image data comprises timing data.

14. A method comprising: receiving, by a processor, time-series image data from an energy application device at a current position and orientation relative to a subject, wherein the time-series image data includes images of internal tissue of the subject at the current position and orientation over time; determining, via the processor, an alignment score of the energy application device with an anatomical target over time based on the image data; comparing, via the processor, the alignment score for a time interval corresponding to the temporal image data at the current position and orientation with a predicted alignment score for the time interval at one or both of additional positions or orientations; as well as A control signal is provided based on the comparison to maintain or change one or both of the position or orientation of the energy application apparatus.

15. The method of claim 14, wherein the method further comprises receiving temporal image data at additional times, and determining a predicted therapeutic dose session time based on the alignment scores over time corresponding to the temporal image data at the additional times.

16. A method according to claim 14, wherein the time-series image data includes image data during a breathing cycle of the subject, wherein the time-series image data is used to monitor the movement of the subject's internal anatomical structure relative to the current position and orientation of the energy application device during the breathing cycle.

17. A tracking system, the tracking system comprising one or more processors and a memory, wherein the one or more processors are configured to execute instructions stored on the memory to perform actions comprising: receiving image data from an energy application device, wherein the image data includes an image of internal tissue based on a current position and orientation of the energy application device relative to the subject; receiving target image data, the target image data including an anatomical target and corresponding to internal tissue of the subject; identifying the anatomical target in an image frame of the image data and tracking the anatomical target in subsequent frames of the image data; determining an alignment score of the energy application device relative to the anatomical target based on the image data; comparing the alignment score to a threshold relative to the anatomical target; as well as Based on the comparison of the alignment score to the threshold, a control signal is provided to maintain or change one or both of the position or orientation of the energy application apparatus.

18. The tracking system of claim 17, wherein the tracking system receives additional data comprising one or more of respiratory cycle data, position of the energy application device over time, or orientation of the energy application device over time.

19. A tracking system according to claim 17, wherein the control signal includes three-dimensional motion data, wherein the three-dimensional motion data indicates one or both of the position or the orientation of the energy application device, the electronic focus of the treatment beam of the energy application device, or movement of both.

20. The tracking system of claim 17, wherein the control signal comprises two-dimensional motion data, wherein the two-dimensional motion data indicates a lateral direction of motion of the energy application device, an electronic focus of a therapeutic beam capable of being delivered by the energy application device, or both.

Images