Ultrasonic beam path determination and targeting

Abstract

To provide ultrasonic beam path determination and targeting.SOLUTION: A target region is irradiated with a therapy beam upon determination or confirmation of at least a partial clear path with respect to some or all of the following factors: (1) the presence of non-soft tissue regions within a therapy beam path (bone or bone-like structures, gas-filled cavities, and so forth); (2) partial "lift-off" of a probe head; and (3) sufficiency of acoustic coupling.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The subject matter disclosed herein relates to identifying, targeting, and / or administering energy (e.g., neuromodulating energy) to a region of interest in a subject to produce a targeted physiological result. In particular, the disclosed techniques can be useful for precisely delivering a known dose to a targeted region. [Background technology]

[0002] Neuromodulation has been used to treat a variety of clinical conditions. However, targeting specific tissues with neuromodulation can be challenging. For example, the precise focus of neuromodulation energy can vary based on an individual patient's anatomy. A particular patient may have variations in organ size and location relative to other patients based on height, weight, age, sex, clinical status, etc., and these variations can affect targeting and dose delivery when using various neuromodulation techniques.

[0003] Other common challenges to delivering accurate ultrasound treatment at a prescribed dose in neuromodulation using ultrasound devices include poor acoustic coupling between the treatment probe and the patient, "lift-off" of portions of the probe from the patient, or the presence of acoustic reflectors or absorbers (e.g., bony structures such as ribs, intestinal gas, etc.) in the treatment beam path. These factors can result in an inaccurate dose or patient discomfort. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Patent Application Publication No. 2010 / 0069753 Summary of the Invention

[0005] The disclosed embodiments are not intended to limit the scope of the claimed subject matter, but rather, these embodiments are intended only to provide a brief summary of possible embodiments. Indeed, the disclosure may encompass a variety of forms that may be similar to or different from the embodiments set forth below.

[0006] In one embodiment, an ultrasonic therapy delivery system is provided. According to this embodiment, the ultrasonic therapy delivery system includes an energy application device configured to deliver ultrasonic energy to a target region within a subject, the energy application device including one or more transducers configured to emit an imaging beam and a therapy beam, and a controller. The controller is configured to perform operations including: activating some or all of the one or more transducers to emit an imaging beam; receiving image data generated in response to the imaging beam; determining whether all or a portion of the target region is present in the image data scanned by the imaging beam; determining, in response to determining that at least a portion of the target region is present in the image data, whether a therapy beam can be applied to the target region to administer all or a portion of a therapeutic dose of ultrasound energy to the target region; and, in response to determining that a therapy beam can be emitted to the target region to administer the therapeutic dose, activating some or all of the one or more transducers to emit the therapy beam and administer all or a portion of the therapeutic dose to the target region.

[0007] In another embodiment, a method for delivering ultrasound therapeutic energy is provided. According to the method, image data of a subject is acquired using an ultrasound imaging beam. A determination is made as to whether all or a portion of a target region for treatment is present in the image data. In response to determining that at least a portion of the target region is present in the image data, a determination is made as to whether an ultrasound therapy beam can be applied to the target region to provide all or a portion of a therapeutic dose of ultrasound energy to the target region. A path of the ultrasound therapy beam at least partially overlaps a path of the ultrasound imaging beam within the subject. In response to determining that an ultrasound therapy beam can be applied to the target region to provide a therapy dose, one or more transducers are activated to emit the ultrasound therapy beam to provide all or a portion of the therapeutic dose to the target region of the subject.

[0008] These and other features, aspects, and advantages of the present invention will be better understood from the following detailed description when read in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a schematic diagram of a routing and therapy delivery system according to an embodiment of the present disclosure. [Figure 2] FIG. 1 is a block diagram of a routing and therapy delivery system according to an embodiment of the present disclosure. [Figure 3] 1 illustrates one embodiment of a static transducer arrangement for use in an ultrasound probe, in accordance with aspects of the present disclosure. [Figure 4] 1 illustrates a further embodiment of a static transducer arrangement for use in an ultrasound probe, according to aspects of the present disclosure. [Figure 5] 10 illustrates an additional embodiment of a static transducer arrangement for use in an ultrasound probe, according to aspects of the present disclosure. [Figure 6] 1 illustrates another embodiment of a static transducer arrangement for use in an ultrasound probe, in accordance with aspects of the present disclosure. [Figure 7] 7 illustrates an example of the transducer arrangement of FIG. 6 emitting a focused treatment beam according to an embodiment of the present disclosure. [Figure 8] 7 illustrates an example of the transducer arrangement of FIG. 6 emitting a focused treatment beam and an imaging beam that encompasses the treatment beam, according to an embodiment of the present disclosure. [Figure 9] 1 illustrates one embodiment of a dynamic transducer arrangement for use in an ultrasound probe, in accordance with aspects of the present disclosure. [Figure 10] 1 illustrates a further embodiment of a dynamic transducer arrangement for use in an ultrasound probe, according to aspects of the present disclosure. [Figure 11] 10 illustrates an additional embodiment of a dynamic transducer arrangement for use in an ultrasound probe, in accordance with aspects of the present disclosure. [Figure 12] 1 illustrates another embodiment of a dynamic transducer arrangement for use in an ultrasound probe, in accordance with aspects of the present disclosure. [Figure 13] 1 illustrates a further embodiment of a dynamic transducer arrangement for use in an ultrasound probe, according to aspects of the present disclosure. [Figure 14] 10 illustrates an additional embodiment of a dynamic transducer arrangement for use in an ultrasound probe, in accordance with aspects of the present disclosure. [Figure 15] 1 illustrates one embodiment of a transducer arrangement for use in an ultrasound probe and subjected to external motion, in accordance with aspects of the present disclosure. [Figure 16] 1 shows a diagram of an ultrasound probe head including an arrangement of peripheral sensors according to aspects of the present disclosure. [Figure 17] 1 illustrates a process flow for detecting a cavitation event according to an aspect of the present disclosure. [Figure 18] 1 illustrates a process flow for making routing decisions and applying therapy according to aspects of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0010] One or more specific embodiments are described below. In an effort to provide a concise description of these embodiments, not all features of an actual implementation are described herein. It should be understood that the development of such an actual implementation, like any engineering or design project, involves numerous implementation-specific decisions that will vary from implementation to implementation in order to achieve the developer's particular goals, including compliance with system-related and business-related constraints. Moreover, it should be understood that such a development effort may be complex and time-consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill in the art having the benefit of this disclosure.

[0011] The examples or illustrations provided herein are not to be considered restrictions on, limits to, or express definitions of any terms or terms with which they are used. Instead, these examples or illustrations are described with respect to various specific embodiments and are to be considered exemplary only. Those skilled in the art will understand that any term or term with which these examples or illustrations are used encompasses other embodiments, whether or not provided therewith or elsewhere in this specification, and that all such embodiments are intended to be included within the scope of that term or term. Language designating such non-limiting examples and illustrations includes, but is not limited to, the following: "for example," "exemplary," "for example," "including," "in particular embodiments," "in some embodiments," and "in one embodiment."

[0012] As discussed herein, one problem that can arise when using image-based techniques to evaluate or guide the application of ultrasound therapeutic energy to a target region within a patient (such as for neuromodulation purposes) is "blind spots," which may correspond to areas of the patient traversed by the treatment beam but not seen by the imaging technique. As used herein, the path of the treatment beam (i.e., the therapy beam path) encompasses objects or structures near the target region as well as the region "from-to-beyond" the target region (i.e., from the transducer to the target region and beyond the target region). For practical purposes, the treatment beam can be envisioned as a cone converging from the transducer to the target region and another cone diverging away from the target region. With regard to blind spots along this path traversed by the treatment beam but not imaged by the imaging beam, these blind spots can lead to treatment modulation "off target" (i.e., affecting or applying energy to patient regions that are not part of the target region) and / or failure to deliver the prescribed dose to the patient. As an example, in the case of a central imaging array and outer treatment arrays applied close to or adjacent to the patient's skin, patient regions near the skin line may not be observed by the imaging arrays but may be traversed by the treatment beam. Such blind spots are problematic in the image-guided therapy context.

[0013] Further challenges in delivering accurate and safe ultrasound treatment using image-guided techniques include poor acoustic coupling between the treatment device and the patient, “lift-off” of portions of the treatment device relative to the patient, and the presence of acoustic reflectors or absorbers in the treatment beam path (e.g., bony structures such as ribs, gas-filled pockets or areas such as intestinal gas). Regarding these factors, poor acoustic coupling may not necessarily appear at the edges of the image, but may manifest as an excessively blurred or dim image, which may be more indicative of a “lift-off” event. Partial “lift-off” is indicated by no image or a dim image along the image edges and can result in heating of the treatment transducer and reduced dose delivery. Acoustic reflection or absorption (e.g., “shadowing”) can occur when the transducer is over a shadow-causing structure (e.g., ribs). These factors can result in inaccurate dosing and / or patient discomfort.

[0014] Furthermore, ultrasound pressure waves generate mechanical forces that are applied to internal tissues. If these mechanical forces become too large, undesired mechanical bioeffects can occur. Ultrasound beams can also heat internal tissues as they absorb the ultrasound energy. Factors such as increased power and effective duty cycle can increase internal heating. Excessive internal heating can result in many undesirable thermal bioeffects. Furthermore, tissue attenuation and acoustic impedance vary across tissue types. For example, bone has attenuation and impedance that are ~15 and ~5 times greater, respectively, than the next highest internal soft tissues. High attenuation can lead to bone heating, and large acoustic impedance differences can result in strong reflections at tissue-bone interfaces, defocusing or redirecting acoustic energy. Furthermore, when internal gas structures are excited by high mechanical forces, they can cavitate, potentially affecting surrounding tissues.

[0015] Because of the issues discussed above, and to ensure accurate dose delivery (and thus effective treatment), it is desirable to know whether there is a “clear” path for the treatment beam path to and beyond the target region. Such path determination or analysis may involve multiple factors (e.g., absence of bone or other dense, acoustically reflective structures, absence of gas-filled cavities, absence of other anatomical structures that are undesirable for receiving some of the ultrasound energy, good acoustic coupling, absence of probe interface “lift-off,” etc.), all of which may or may not be considered in a given path determination. The factor(s) considered depend on considerations such as the treatment protocol, patient anatomy, system geometry, and the given frequency and / or dose. Furthermore, in some embodiments, the path determination or analysis may span acceptable ranges for some or all of the various factors considered, alone or in combination; in such cases, the determination may be a graded or quantified clearance metric rather than a simplistic binary “clear / not clear” determination. In such contexts, the determined degree of "clear" path may in turn be utilized to determine appropriate next steps, such as notifying the user to reposition and / or reorient the energy application device, or electronically manipulating application device elements to utilize the path determination information, e.g., adjusting the power level at which the device is operated, sweeping one or more transducers within the device to adjust the path, selectively activating a subset of available transducers, etc.In practice, the evaluation and use of path determination may be based on, in either a binary or graded form, safety criteria, therapeutic dose criteria (e.g., based on the degree and characteristics of the therapeutic dose that can be applied given the observed clear path measurements, based on predictive analysis, how much dosage energy or power will be delivered to the target area and what the ultrasound beam profile looks like (i.e., where spatially will the energy be delivered? Does the beam look like a normal focused beam, do obstacles cause the energy to defocus into a larger area, or does the beam shift to an unintended location?), and / or efficacy thresholds (e.g., that the dosage that can be applied to the target area along the evaluated path will deliver sufficient dosage or energy to exceed a specified threshold effectiveness, based on what can be delivered given any obstacle(s) and the beam characteristics being evaluated, as well as clinical factors such as the specific target anatomy, patient, and prescription).

[0016] As discussed herein, various factors may be considered as part of path determination or analysis, but in certain embodiments, such determination may include (primarily or as a component) a determination that the target region for treatment is “visible” (i.e., lies within the imaging beam) and therefore accessible to the treatment beam. As an example, an initial aspect of path determination or analysis is whether the target region lies (partially or completely) within the path imaged by the imaging beam. In such situations, the absence of any portion of the target region within the imaging region seen by the imaging beam may preclude evaluation of further factors. That is, if the target region is not visible to the imaging beam, it may be presumed that there is no path for the treatment beam to the target region, and further path consideration may be ignored. In some contexts, an evaluation of whether the target region is visible to the imaging beam may be the only consideration. In other embodiments, additional factors (e.g., “lift-off” events, acoustic coupling) may be evaluated so long as some or all of the target region is visible to the imaging beam. Additionally, the extent (if less than total) of the target area visible to the imaging beam can be compared to a threshold for effectiveness or a therapy dose criterion to determine whether the available pathways are sufficient to apply a therapy beam along the pathway.

[0017] With this in mind, the techniques and approaches discussed herein comprise combinations of physical embodiments and control / analysis schemes that can be employed to provide safe and precise delivery of ultrasound therapy to a target. Indeed, while the presently described techniques and approaches are useful for trained technicians to administer ultrasound therapy treatments to target areas of a patient, these techniques and approaches can also be employed to enable medically untrained individuals, including the patient themselves, to safely administer ultrasound therapy treatments while achieving the desired medical effect without risk of injury.

[0018] To that end, the disclosed beam path analysis and determination techniques can be used in conjunction with an ultrasound therapy system (e.g., a neuromodulation system) configured to deliver ultrasound energy as part of a treatment protocol. By way of example, FIG. 1 is a schematic diagram of a neuromodulation system 10 for achieving a neuromodulatory effect, such as neurotransmitter release and / or activation of synaptic components (e.g., presynaptic cells, postsynaptic cells) in response to the application of energy. The depicted system includes a pulse generator 14 coupled to an energy application device 12 (e.g., an ultrasound transducer). The energy application device 12 is configured to receive, e.g., via a lead or wireless connection, or otherwise generate energy pulses that, in use, are directed to a target region within a subject's internal tissue or organ, resulting in a targeted physiological outcome (e.g., release of neurotransmitters, proteins, etc.).

[0019] In certain embodiments, the energy application device 12 and / or the pulse generator 14 may communicate wirelessly with a controller 16, which may, for example, provide instructions to the pulse generator 14. In other embodiments, the energy application device 12 may be an extracorporeal device, e.g., operable to apply energy transdermally or noninvasively from a location outside the subject's body, and in certain embodiments, may be integrated with the pulse generator 14 and / or the controller 16. In embodiments in which the energy application device 12 is extracorporeal, the energy application device 12 may be operated by a caregiver or the patient and positioned at or above the subject's skin so that energy pulses are delivered transdermally to desired internal tissues. Once positioned to apply energy pulses to the desired site, the system 10 can initiate neuromodulation of one or more neural pathways to achieve a targeted physiological result or clinical effect. In some embodiments, the system 10 may be implemented such that some or all of the elements may communicate with each other via wires or wirelessly.

[0020] In certain embodiments, the system 10 may include an assessment device or logic 20 coupled to the controller 16 that evaluates characteristics indicative of whether a clear or sufficient path to the target region exists relative to the placement and orientation of the energy application device 12. As used herein, such path analysis may include some or all of the following: determining sufficient acoustic coupling; determining the absence of "lift-off" where a portion of the probe is not in contact with the patient; and determining the absence or limited presence of blocking anatomical structures or structures (e.g., bone or bone-like structures, gas-filled cavities, etc.) between the probe and the target region. In one embodiment, the assessment device or logic 20 may utilize different frequencies of ultrasonic energy emitted by the same or different transducers of the energy application device 12 to perform treatment and imaging. In other embodiments, the treatment and assessment frequencies of ultrasonic energy may be emitted by different transducers (e.g., an imaging transducer and a treatment transducer) or structures of the energy application device 12. Additionally, non-image sensing modalities (e.g., electrodes, pressure sensors, cavitation sensors, etc.) can also generate data or measurements useful in determining one or more pathway factors being evaluated.

[0021] Based on the path evaluation, the delivery of therapeutic ultrasound energy is automatically altered, modulated, or directed to achieve a predetermined therapeutic result. Additionally or alternatively, instructions or guidance may be provided to the user, such as via audible or visible indicators, to indicate the presence or absence of a sufficiently clear or suitable path for the therapeutic ultrasound energy, or to provide guidance regarding the placement and / or orientation of the energy application device 12 to achieve such a path.

[0022] The system 10 provided in this example can provide energy pulses according to various modulation parameters as part of a treatment protocol for applying an effective amount of energy. For example, modulation parameters can include various stimulation time patterns, ranging from continuous to intermittent. In intermittent stimulation, energy is delivered at a certain frequency for a period of time during a signal-on time. The signal-on time is followed by a period of time during which no energy is delivered, called a signal-off time. Modulation parameters also include the frequency and duration of stimulation application. The application frequency can be continuous or applied over various time periods, for example, within a day or week. Furthermore, the treatment protocol can specify the time of day during which energy is applied, or relative to meals or other activities. Treatment durations to induce a desired physiological result can last for various periods of time, including, but not limited to, from several minutes to several hours. In certain embodiments, treatment durations with a particular stimulation pattern can last from one minute to one hour and can be repeated at regular intervals (e.g., 72-hour intervals). In certain embodiments, energy may be delivered more frequently (e.g., every 2 or 3 hours) for shorter durations (e.g., 1 minute). The application of energy according to modulation parameters such as treatment duration, frequency, and amplitude may be adjustably controlled to achieve desired results.

[0023] FIG. 2 is a block diagram of certain components of one embodiment of system 10. In particular, aspects and components of one embodiment of system 10 are illustrated as modules corresponding to certain functionality described above with respect to energy applicator 12, pulse generator 14, assessment component 20, and / or controller 16. For example, the block diagram of FIG. 2 illustrates a treatment module 40 and a probe module 42 that may be used to perform the functions described herein with respect to FIG. 1. While an imaging module 44 is also illustrated, it will be understood that in certain embodiments, such an imaging module 44 may not be present. In such alternative embodiments, analysis performed on data acquired at what may be understood as imaging frequencies of ultrasound energy may be performed on unreconstructed (i.e., raw) imaging data, without reconstruction into an image or analysis performed on the image. As an example, path determination or analysis as discussed herein using imaging transducer 52 or based on data acquired by imaging module 44 may be based on reconstructed images (e.g., signatures within the reconstructed data) or may be based on ultrasound signatures present in unreconstructed image data.

[0024] Describing first the probe module 42, in the depicted example, the probe module 42 includes a transducer 50. In the depicted example, the transducer 50 includes both an imaging transducer 52 (operating at a certain frequency or frequency range) and a therapy transducer 54 (which may operate at the same frequency as the imaging transducer 52 or at a different frequency range). In one embodiment, the transducer 52 may include 128 imaging transducers and 4 therapy transducers, although other quantities or types of transducers may alternatively be employed. In the simplified case of ultrasound signal transmission, ultrasound may be transmitted and received continuously through an area or defined portion of the imaging transducer array and / or the therapy transducer array.

[0025] In alternative embodiments, transducer 50 may instead be comprised of one or more types of transducers 52 operable at both imaging and therapy frequencies, such that separate transducers are not provided for each type of operation. By way of example, transducer 52 in this context may be configured to operate at the same frequency or frequency range for both imaging and therapy operations, or may be configured to operate at a first frequency range for imaging and a second frequency range for therapy. In such embodiments, a single transducer or transducer type may be operable to both provide therapy and acquire imaging-type data used in determining the clear pathway discussed herein. Such a single transducer type approach may be appropriate when the target region is shallow and / or high power output is not required.

[0026] With respect to the imaging transducer 52 and the therapy transducer 54, in practice, the imaging transducer 52 may operate at a higher frequency and / or have a smaller aperture size relative to the therapy transducer 54. In contrast, the therapy transducer 54 typically operates at a lower frequency (to reduce attenuation) and / or over a larger area (for greater focusing gain) to deliver more power to a deeper target. In one embodiment, the therapy transducer 54 may operate at a frequency between 0.2 MHz and 2 MHz (e.g., 0.5 MHz or 2 MHz). In such an embodiment, the therapy transducer(s) 54 may be constructed from a suitable material, such as a piezoelectric material, such as, but not limited to, PZT-4. In one embodiment, the imaging transducer(s) 52 may operate in a frequency range between 2 MHz and 12 MHz (e.g., 3 MHz to 10 MHz or 5 MHz to 12 MHz). In such an embodiment, the imaging transducer(s) 52 may be constructed from a suitable material such as, but not limited to, a piezoelectric material such as PZT-5.

[0027] In the depicted example, the probe module 42 also includes a hardware controller 60, which in the depicted example includes a microcontroller (MCU) 62 in communication with a master controller (e.g., processor) 110 of the treatment module 40, and a field programmable gate array (FPGA) 64 in communication with the MCU 62 and sensors 70 and / or actuators 80 associated with the probe module 42. In this configuration, the MCU 62 and FPGA 64 can be in bidirectional communication with components of the master controller 110 (e.g., data logger 122) to coordinate and / or record operation of aspects of the probe module 42 or components directly or indirectly associated with the probe module 42, such as the actuators 80 and / or sensors 70. While shown as part of the probe module 42 in FIG. 2 , it should be understood that some or all of the actuators 80 and / or sensors 70, if present, may be provided separately from or external to the probe module 42, for example, as separate parts or components. Alternatively, some or all of the actuator 80 and / or sensor 70, if present, are provided within or integral with the probe module 42.

[0028] With respect to the actuator 80, in the depicted example, the actuator may include one or both of a first motor 82 and a second motor 84. One or both of the motors may be configured to move the probe module 42 itself and / or separate aspects of the probe module 42, such as the imaging transducer 52 and / or the therapy transducer 54. The motors 82, 84 may be configured to effectuate movement of the probe module 42, the imaging transducer 52, and / or the therapy transducer 54 in an automated manner, particularly in response to signals from an FPGA 64 provided as part of the hardware controller 60, thereby allowing communications received from the therapy module 40 to control the movement of the respective components. Additionally, as shown in FIG. 2 , in certain embodiments, a manual adjustment mechanism 86 (e.g., a patient-specific manual adjustment), such as a belt, cinch, manual placement interface, or the like, may be provided to allow manual adjustment or movement of the probe module 42 relative to an interface area on the patient.

[0029] With regard to the sensors 70, various types of sensors may be integrated with the probe module 42 or, if separate, may be in communication with the probe module 42. By way of example, the sensors 70 may include one or more of a respiration sensor, a posture and motion sensor, electrodes, pressure sensors, accelerometers, and / or a safety sensor. For example, a respiration sensor may be used to obtain quantitative or qualitative data related to the patient's respiration, thereby identifying periods of respiratory motion, which is useful for identifying times when routing or analysis can or should be performed or therapy can be applied. Similarly, a posture and motion sensor may be used to identify the patient's voluntary or involuntary movement, the patient's position, and the patient's posture or orientation. Such information may also be used to identify when routing or analysis can or should be performed or therapy can be applied. The safety sensor may be calibrated to send a signal when a safety condition or threshold is violated. Thus, signals from this sensor can be used to control (e.g., stop) operation of the probe module 42 until the safety condition is again met. Additionally, as discussed herein, electrodes, pressure sensors, and other such sensors can be employed to determine or analyze certain factors that may contribute to a path analysis or decision routine (e.g., determining the sufficiency of acoustic coupling, determining whether a "lift-off" event has occurred, etc.). Such sensor data can be employed in addition to, or instead of, analyzing image data to determine whether these conditions exist, or if so, to what extent. As shown in FIG. 2, one or more sensors 70, if present, may be communicatively coupled to the FPGA 64 or other hardware controller 60.

[0030] With respect to the treatment module 40, as previously mentioned, an implementation of the treatment module 40 may include a master controller (e.g., processor) 110, which may itself include or execute various sub-modules or routines. In this example, the master processor includes or executes modules or routines that provide the functionality of an image streamer and remote control 112, an artificial intelligence (AI) anatomical recognition and tracking 114, a guided dosing engine 116, a user interface 118, support analytics 120, and a data logger 122, and is shown in this example to be in communication with the MCU 62 or probe module 42.

[0031] Like the probe module, in certain embodiments, the therapy module 40 may include a hardware controller 126 that includes its own MCU 122 and FPGA 124. While depicted as separate modules for purposes of illustration and description, in practice the probe module 42 and therapy module 40 may actually be integrated (i.e., a unitary structure or device configured to perform the functions of both a therapy module and a probe module, as described herein). With this in mind, although discussed separately herein, in practice the hardware controllers 60 and 126 may be implemented as a single hardware controller. In the depicted example, the MCU 122 is depicted in communication with the master controller 110 and its components and modules. The FPGA 124 communicates with and / or controls other components of the therapy module, such as therapy pulser-receivers 130 (depicted in communication with the therapy transducers 54 of the probe module 42), safety circuitry 132, and / or power management circuitry 134.

[0032] During execution, the master controller 110, in conjunction with the hardware controllers 60, 126, can control the operation of the therapy module 40 and the probe module 42 to perform path determination and analysis in addition to applying therapy according to the processes and structures described herein. As an example, the master controller 110, in some embodiments, may be used to perform path determination or analysis as described herein, and may cooperate with the hardware controllers 126, 60 to electronically interleave the imaging and therapeutic ultrasound pulses generated by the transducer 50 to perform dual imaging / therapy functions, and / or control the operation of the transducer 50 and / or the probe module 42 (such as using one or more of the motors 82, 84). In this aspect, the master controller 110 can control ultrasound therapy administration sequences, including gated dosage delivery, based on detection of a suitable or acceptable path. In some embodiments, the master controller 110, such as through module 114, can establish and track an anatomical context used to evaluate a path, such as when moving the imaging transducer(s) 52 within the probe module 42 or relative to the patient's anatomy.

[0033] In the depicted embodiment, the imaging module 44 is also depicted as a component of the overall system. Such a module, if present, may control or monitor the operation of the transducer 50 (e.g., the imaging transducer 52) to control the generation, collection, and / or processing (e.g., reconstruction) of imaging data. In the depicted embodiment, the imaging module 44 is also shown in communication with the master controller 110 of the treatment module 40, particularly the image streamer and remote control sub-module 112, which may control the operation of the imaging module 44 or respond to feedback and data from the imaging module 44. As with the probe module 42 and treatment module 40 described above, the imaging module 44 is depicted in FIG. 2 as a separate module for ease of illustration and explanation of functional concepts. However, as with the previous embodiments, the imaging module 44 may actually be integral with one or both of the probe module 42 and treatment module 40 (i.e., may be a unitary structure or device configured to perform the combined functions of the imaging module and one or both of the treatment module and probe module, as discussed herein).

[0034] With the foregoing system description in mind, in this context, the present technology relates to an image (or non-reconstructed image data) guided ultrasonic therapy system. In certain embodiments, such a system may utilize separate imaging and therapy transducers 52 and 54. Alternatively, in other embodiments, a single transducer or combined transducer may be utilized for both imaging and therapy ultrasound energy applications. In embodiments in which separate imaging and therapy transducers 52 and 54 are employed, the transducers may be optimized for their respective purposes and operationally interleaved by using the imaging transducer 52 to localize an internal anatomical target and the therapy transducer 54 to deliver an ultrasound dose to the target once localized. This process may be repeated until an accumulated dose amount is reached.

[0035] Challenges to delivering accurate and safe ultrasound treatments include poor acoustic coupling between the energy applicator and the patient, "lift-off" of portions (e.g., edges or corners) of the applicator from the patient during treatment, the presence of obstacles in the treatment beam path, such as acoustic reflectors or absorbers (i.e., bones or ribs, gas-filled cavities), and / or differences in acoustic properties around the target tissue that aberrate the path of the ultrasound beam and impede or prevent treatment. Such factors can result in inaccurate delivery of the dose and / or interfere with treatment, patient discomfort, or unintended off-target effects. With this in mind, as described herein, certain physical and algorithmic aspects of ultrasound treatment delivery systems have been developed that can be employed to ensure a problem-free path (e.g., absence of bone or bone-like structures, gas-filled pockets or cavities, etc., good acoustic coupling, and no "lift-off") for the treatment beam to propagate from the probe exit face to the target region and beyond, thereby providing accurate administration and patient safety. Furthermore, such techniques can be employed when ultrasound-based treatments are administered by trained technicians or medical personnel, or by untrained personnel, including patients, allowing untrained personnel to effectively deliver a predetermined dose to a target area without risk of injury.

[0036] As an example, in one embodiment, the imaging transducer(s) 52 and the therapy transducer(s) 54 are arranged in an offset or standoff configuration, with the active area of ​​the imaging beam including the active area of ​​the therapy beam at the point of entry into the body (i.e., the interface formed by the skin surface and the probe exit face). Using such a configuration, the above-mentioned problems can be mitigated by analysis of the ultrasound image data or reconstructed images. For example, poor coupling can manifest as abnormally low image quality or missing portions of the image, "lift-off" often results in partially blacked-out portions of the image, and bones in the treatment path are seen as large reflectors in the image that also black out areas behind them. Thus, in some embodiments, the probe is physically configured such that the geometries of the therapy transducer(s) 54 and imaging transducer(s) 52 ensure intersection of the imaging and therapy beams. A processor-executable routine is then employed in an automated manner to identify or otherwise detect some or all of the above-mentioned problematic symptoms in the ultrasound image (or raw image data) to ensure safe and accurate delivery. In some embodiments, one or both of the imaging transducer 52 or therapy transducer 54 may be moved (either by internal or external motion or motor), such as based on signals or control routines generated by associated master control and image analysis routines, to ensure a clear path. In other embodiments, abbreviated ultrasound pulse sequences or alternative sensor data are used to determine one or more criteria for determining a clear path.

[0037] With this in mind, various exemplary embodiments are described herein for using reconstructed or raw image data in conjunction with a therapy beam (e.g., an ultrasound therapy beam) to apply a therapy or treatment, such as neuromodulation therapy. The various exemplary embodiments illustrate different imaging transducer 52 and therapy transducer 54 shapes and orientations, internal and external movement options for the transducer assembly, control schemes that ensure the imaging beam substantially or completely encompasses the full acoustic window of the therapy beam, and algorithmic concepts that analyze image data and / or sensor data to make clear path decisions.

[0038] A first embodiment is characterized as a static transducer configuration, examples of which are shown in Figures 3-5. In certain such implementations, the imaging transducer 52 and therapy transducer 54 reside within a probe that includes a cap 150 (e.g., a sonolucent cap) configured to contact the patient during use. That is, the imaging transducer 52 and therapy transducer 54 are separated from the patient during use by the cap 150 and an internal standoff 152 that separates the transducers from the cap 150. The standoff 152 is sized or dimensioned to ensure coverage of the therapy beam path by the imaging beam after the patient interface (i.e., blind spots are moved within the space encompassed by the cap 150). Because there is no movement of the transducer elements in static configurations, the internal standoff 152 in these and other static transducer configurations may be constructed of a solid or fluid material.

[0039] Three such static transducer examples are shown in Figures 3-5. In these three figures (and subsequent configuration figures), three different views corresponding to each configuration are shown: (1) a top view corresponding to the acoustic window, (2) an azimuth view, and (3) an elevation view rotated 90° relative to the azimuth view.

[0040] 3 depicts a side-by-side transducer configuration in which an array of imaging transducers 52 is arranged in a linearly adjacent configuration with a pair of arrays of therapy transducers 54. The extent of the imaging beam 160 and therapy beam 162 produced in this configuration is illustrated in this example. As shown in this example, in this configuration, due to the offset between the transducers 50 and the patient interface or contact location, there is overlap of the therapy beam 162 with the imaging beam 160 outward from the patient interface (i.e., cap 150). That is, in the direction of propagation of the therapy beam 162 from the cap 150 into the patient's body, the path traversed by the therapy beam 162 is fully encompassed within the imaging beam 160.

[0041] Turning to FIG. 4 , a co-centric transducer configuration is illustrated that provides partial overlap of the treatment beam 162 with the imaging beam 160, working outward from the patient interface (i.e., cap 150). Notably, as seen in the bottom elevation view, the treatment beam 162 is partially outside the range of the imaging beam 160 near the skin surface (i.e., near the cap 150), but is encompassed by the imaging beam 160 at greater depths. Such an approach may be preferable in contexts where routing or evaluation criteria are relaxed to ensure that a substantial proportion (e.g., 70%) of the energy density of the treatment beam 162 is intersected at the skin surface by the imaging beam 160.

[0042] Turning to Figure 5, an embodiment is depicted employing an electronic real-time three-dimensional (e4D) imager (e.g., an array of imaging transducers 52) that can be steered in the XY dimensions to fully intersect the treatment beam 162 in a series of consecutive images. The depicted example shows a co-centric transducer configuration with the e4D image transducer array centrally located, although a side-by-side configuration is also suitable. The steerability of the imaging beam 160 effectively provides full coverage of the range of the treatment beam 162.

[0043] With the foregoing in mind, FIGS. 6-8 depict further examples of static transducer embodiments, in which the imaging transducers 52 may be provided as one or more annular rings around the perimeter of the probe face (i.e., as an annular imaging transducer array). In certain implementations, the array of imaging transducers 52 may be provided as a sparse 2D array that utilizes fewer channels compared to a fully sampled 2D array and supports high-quality volumetric imaging using techniques such as synthetic aperture beamforming. This perimeter imaging array facilitates verification of complete contact between the probe 42 and the skin surface 200, as discussed herein. Within the annular imaging transducer array, annular and circular treatment transducers 54 are concavely arranged (i.e., a multi-element treatment transducer array). This arrangement maximizes the active high-intensity focused ultrasound (HIFU) aperture area and can be seen in the perspective view of FIG. 6.

[0044] 7 depicts this same arrangement, but illustrates the treatment beam 162 produced by the treatment transducer 54. In this depiction, the cone-shaped treatment beam 162 is shown focused to a focal spot 56 that can be used to target a target region. In one embodiment, the treatment transducer 54 can be phased to provide a variable or configurable focal depth, as indicated by the movement arrows associated with the focal spot 56 in FIG. 7.

[0045] 8, both the treatment beam 162 and the image beam 160 are shown together to provide further context and to illustrate that the range of the image beam 160 exceeds the range of the treatment beam 162. Additionally, because an annular imaging transducer array is disposed around the periphery of the patient-contacting surface of the probe and, in the illustrated embodiment, due to the convex (i.e., dome-shaped) patient-contacting surface, probe "lift-off" events can be detected using the imaging transducer array. That is, in the absence of complete contact, lift-off artifacts may be observed in the acquired image data, and a warning or treatment halt may be initiated.

[0046] While Figures 3-8 depict static transducer arrangements, other embodiments are contemplated in which either or both of the imaging transducer 52 or the therapy transducer 54 move during operation (i.e., dynamic transducer arrangements). For example, Figures 9-13 depict examples of what may be characterized as "dynamic" transducer configurations in which either or both of the imaging transducer 52 or the therapy transducer 54 move during operation. As an example, Figures 9 and 10 depict an example in which the imaging transducer 52 and the therapy transducer 54 are provided as a rectangular array (encoded by a rectangular acoustic window 180) that moves in and out of position for operation. Due to the movement of the transducer elements, the internal standoffs 152 of these and other dynamic transducer configurations may be filled with fluid.

[0047] With this in mind, FIG. 9 illustrates an example in which the array of imaging transducers 52 and therapy transducers 54 are alternately moved into operating positions by an internal pendulum (having pendulum arms 182), essentially swinging the imaging transducers 52 and therapy transducers 54 back and forth so that one set of transducers is in an operating position (i.e., within the acoustic window 180) while the other set is not. Similarly, FIG. 10 illustrates another embodiment in which a linear or rotational motion stage is employed (indicated by linear motion arm 184) to move the imaging transducers 52 and therapy transducers 54 between operating positions such that only one set of transducers is in an operating position (i.e., within the acoustic window 180) at a time. As shown in both embodiments, the image beam 160 fully encompasses the therapy beam 162 from both the azimuthal and elevation perspectives.

[0048] Another dynamic transducer configuration is depicted in FIG. 11. In this example, the array of therapy transducers 54 is provided as a fixed annular array with a rotatable array of imaging transducers 52 positioned in the empty central region of the ring structure. The imaging transducer array 52 in this example is configured to at least partially rotate about an axis during operation to sweep the image beam 160 to cover the entire range of the therapy beam 162 during the image sweep. By way of example, in one embodiment, the array of transducers 52 can rotate or oscillate (depicted by the motion arrow 186) ±90° about a central axis through the ring structure formed by the array of therapy transducers 54. In this manner, each sweep of the image beam 160 generated by the imaging transducer 52 encompasses the range of the therapy beam 162 in both azimuth and elevation.

[0049] Figures 12 and 13 depict two additional generally annular therapy transducer arrays for use in dynamic transducer configurations. In these embodiments, the therapy transducer array structure is elliptical, as opposed to circular (although a circular array structure may alternatively be employed), but retains a central aperture within which the array of imaging transducers 52 is positioned. In contrast to the embodiment of Figure 11, in which the array of imaging transducers 52 rotates within a plane defined by the annular array of therapy transducers 54, in these embodiments the array of imaging transducers 52 is tilted relative to the plane formed by the therapy transducers 54 (depicted by motion arrows 188) so as to sweep in elevation during operation. The embodiments of Figures 12 and 13 differ in whether the array of therapy transducers 54 is tilted (Figure 13) or not (Figure 12) with the imaging transducer array.

[0050] For example, turning to Figure 12, in this embodiment, the array of therapy transducers 54 is fixed (i.e., does not rotate) relative to the central tiltable array of imaging transducers 52 so that the imaging beam 160 can be tilted (i.e., swept) in elevation during operation. In this example, the maximum tilt angle allows the imaging beam 160 to view the farthest extent that the therapy beam 162 enters the patient, as shown in Figure 12. In this manner, the imaging beam 160 can be swept across the entire active area of ​​the therapy beam 162.

[0051] 13 illustrates a similar arrangement, but the array of therapy transducers 54 and the array of imaging transducers 52 are fixed or bonded so that they move (i.e., tilt) together in the elevation dimension. Simultaneous tilting of the imaging beam 160 and the treatment beam 162 allows the imaging beam 160 to view the entire acoustic window intersected by the treatment beam 162. In this example, the maximum tilt angle allows viewing of the furthest extent to which the treatment beam 162 enters the patient, as shown in FIG. 13.

[0052] In procedures employing this arrangement, the treatment beam 162 can be switched off while the transducers are jointly tilted so that path evaluation can be performed using the imaging beam 160. For example, the controller or control circuitry can sequence the movement (e.g., tilt) of the transducer array to facilitate path determination or analysis. Once the path has been determined and / or confirmed to be acceptable, the controller or control circuitry can re-center the transducer array and turn on the treatment beam 162.

[0053] Turning to FIG. 14 , a further dynamic embodiment is illustrated in a side cross-sectional view. This example depicts the body of the probe 42, which can be attached to a patient, such as by a belt or other attachment device, to secure or position the probe 42 to the patient at a treatment site. In the depicted embodiment, the treatment transducer 54 is moved (e.g., oscillated) internally (i.e., within the probe) to cause movement of the treatment beam 162. However, the imaging transducer 52 is fixed in place, and the imaging beam 160 does not move correspondingly. However, the imaging beam 160 encompasses the range of motion of the treatment beam 162 during use.

[0054] With this embodiment in mind, an example of the use of such a configuration can be provided. In this example, the probe 42 may be roughly aligned to the treatment site, such as within ±2 cm (plus or minus 2 cm) in the X and Y dimensions, using a belt, harness, or other attachment mechanism. The field of view of the imaging beam 160 is wide enough to encompass the range of motion of the treatment beam 162. In one embodiment, the therapy transducer 54 is mechanically controlled within a range of ±15° (plus or minus 15 degrees) in the X dimension and electronically focused within a range of ±4 cm (plus or minus 4 cm) in the Z dimension. Such a range of motion and focusing is suitable for targeting a target region at a depth of 8 cm ±4 cm (plus or minus 4 cm). Such a configuration may be useful to enable coarse placement of the probe 42 with targeting and therapy logic to perform clear path determination and targeting of the target region using the imaging beam 160 and / or to enable automated movement and tracking of a target region subject to internal motion, such as due to respiration and / or cardiac motion.

[0055] In the previous embodiments, mechanisms internal to the probe 42 (e.g., motors 82, 84) are utilized to cause movement within the probe 42 of one or both of the imaging transducer 52 or therapy transducer 54 arrays. The internal movement of the transducer array is used to move or scan the imaging beam 160 over the target area through which the therapy beam 162 passes. Turning to FIG. 15 , in a further alternative, the motion applied to the transducer may instead be an external force (i.e., motion caused by a force applied externally to the probe or probe body itself, as opposed to being applied internally to the transducer array), including user-induced manual movement or an external motor provided on the mounting or mounting structure.

[0056] In FIG. 15, the depicted structure is similar to that shown in FIG. 13, except that the imaging transducer 52 and therapy transducer 54 arrays are fixed in place within the head of the probe 42. Instead, movement of the transducers 50 relative to the patient is achieved by external movement of the probe 42. That is, the depicted embodiment is essentially a static transducer structure subject to dynamic external motion, which may be provided by external motors within the probe mount and / or by user-guided manual motion. In this embodiment, in elevation views, the imaging transducer 52 and therapy transducer 54 are shown in the context of the head or contact portion of the probe 42. The probe 42 can be translated and / or tilted, for example, by application of external forces or motions to sweep the image beam 160 over the potential treatment region under evaluation, taking into account a clear path. As an example, in one embodiment, the probe 42 can be moved in one or more degrees of freedom relative to the patient's skin 200 so that path analysis or evaluation can be performed before or during application of the treatment beam 162.

[0057] The preceding discussion generally relates to the use of both an imaging transducer 52 and a therapy transducer 54 within an ultrasound probe to provide ultrasound therapy. As previously mentioned, other sensors or sensing arrangements may be employed in certain embodiments to better identify and address specific issues. With this in mind, turning to FIG. 16, a patient-facing surface of an ultrasound probe head including a sensor 70 is shown. In this example, co-centric image transducers 52 and therapy transducer 54 are shown in accordance with certain prior examples for illustrative purposes, but the present discussion may be relevant to other examples, as can be appreciated. Thus, the image and therapy beams generated by the respective transducers may fully or partially overlap in use. The sensor 70 depicted in this example is provided as a ring-shaped sensor around an acoustic window.

[0058] In one embodiment, some or all of the sensors 70 are electrodes and can be used to perform a “lift-off” check and / or an acoustic coupling check. For example, in the context of a “lift-off” check when the sensors 70 are electrodes, the impedance of each electrode can be measured in an open circuit configuration, such as at system startup. The impedance of each electrode may be measured again when the probe is placed in contact with the patient prior to treatment. A check (e.g., a one-to-one check) may then be performed on each electrode to determine whether the impedance of each electrode has dropped significantly within the expected impedance range for full electrode contact or within the expected impedance range. That is, the initial impedance value of each electrode is compared to the post-contact impedance value of each electrode to ensure that the drop in impedance exceeds a threshold determined to indicate full contact. Electrodes may also be checked or compared to ensure they have similar impedance values. A comparison of impedance values ​​indicating poor contact or “lift-off” may result in a warning or instruction to reposition the probe. Conversely, a comparison of impedance values ​​indicating good contact and / or lack of "lift-off" may initiate treatment or contribute to an evaluation of the current path of the treatment beam.

[0059] In another embodiment in which the sensor 70 is an electrode, an acoustic coupling check may be performed. In this example, when the probe is applied to the patient's body prior to treatment, current may be transmitted from one electrode to another across the probe face (i.e., the acoustic aperture). For example, a current excitation pattern may be employed such as from electrode A to electrode E, electrode B to electrode F, electrode C to electrode G, and electrode D to electrode H. For each current excitation pattern, the measured impedance is compared to the range of impedance expected for perfect gel coupling across the acoustic aperture (i.e., the range of impedance values ​​assuming good acoustic coupling and gel application across the aperture). A good degree of acoustic coupling will result in a low impedance value, as the current pattern will not penetrate the body much but will instead flow across the gel layer on the skin surface. Conversely, an impedance value above a predetermined threshold may indicate poor acoustic coupling, requiring the application of more acoustic gel and / or repositioning of the probe. However, if the measured impedance value is below the threshold, acoustic coupling is acceptable and treatment can proceed.

[0060] In further embodiments, sensors 70 may instead be pressure sensors. In such embodiments, the pressure sensors may be used to perform a "lift-off" check. In such embodiments, each pressure sensor is initially calibrated or re-calibrated for a "non-contact" configuration, such as at system startup. The contact force at each pressure sensor may then be measured when the probe is applied to the patient's body prior to the start of a treatment session.

[0061] A check (e.g., a one-to-one sensor check) can then be performed on each pressure sensor to ensure that the contact force measured when the probe is in contact with the patient indicates full contact around the entire perimeter of the acoustic opening. That is, the initial contact force of each pressure sensor is compared to the post-contact force of the respective pressure sensor to ensure that the measured contact force exceeds a threshold determined to indicate full perimeter contact. Contact force measurements indicating poor contact or "lift-off" can result in a warning or indication to reposition the probe. Conversely, contact force measurements indicating good contact and / or no "lift-off" can initiate treatment.

[0062] In further embodiments, the sensor 70 may instead be a passive cavitation detection sensor. In such embodiments, cavitation detection can be used to monitor the occurrence of acoustic cavitation to avoid tissue damage. Acoustic cavitation is the growth and collapse of pre-existing microbubbles under the influence of an ultrasonic field in a liquid. Cavitation has two stages: non-inertial cavitation and inertial cavitation. Non-inertial cavitation is a process in which small bubbles in a liquid are forced to vibrate in the presence of an acoustic field when the strength of the acoustic field is insufficient to cause the bubbles to completely collapse. Inertial cavitation is a process in which bubbles violently collapse due to the inertia of the fluid. These two stages of cavitation can be detected by the cavitation detection sensor. Turning to FIG. 17 , in such an embodiment, the cavitation sensor can be a single-element ultrasonic sensor or one channel of an imaging array with a selected / calibrated frequency range. The cavitation sensor can transmit / receive a single-beam (A-line) ultrasonic signal (step 250). The received A-line signal (e.g., a time-domain signal) 252 can then be processed (step 254). The signal processing procedure can include converting the time-domain signal 252 to a frequency-domain signal 256 by performing a Fourier transform on the A-line signal. The frequency-domain signal 256 can be monitored for the appearance of harmonics, subharmonics, and broadband noise in the frequency-domain signal. The appearance of harmonics and subharmonics can indicate the occurrence of non-inertial cavitation 264. The appearance of broadband noise can indicate the occurrence of inertial cavitation 262.A check (e.g., a one-to-one sensor check) may then be performed on the cavitation detection sensor to ensure that the acoustic field is below the cavitation threshold and it is safe to perform treatment (step 266).

[0063] While the foregoing describes various exemplary structural embodiments and transducer configurations suitable for clear path determination, FIG. 18 depicts a sample process flow illustrating steps involved in using certain of these embodiments. As an example, FIG. 18 relates to steps that may be suitable for performing image-based path evaluation and corresponding therapy delivery. Turning to the illustrated process flow, image data 302 is first acquired (step 300) using the imaging transducer 52 (or associated transducer 50) of each probe structure 42. The image data 302 (either in the form of a reconstructed image or as unreconstructed raw data) may be analyzed (decision block 306) to determine whether all or a portion of the target region is visible or otherwise present in the image data. In practice, this determination 306 may be based on a threshold target region visibility 310 (e.g., percent visibility), which may be specified by the user based on the treatment protocol, patient anatomy or demographics, and so forth. Moreover, in practice, such threshold visibility may be based on a raw percentage (e.g., 50% visibility, 75% visibility, 95% visibility, etc.) based on whether certain protocol-specific features of the target region are visible, based on one or more of the efficacy criteria, which may be a function of percent visibility, the range of treatment energies that can be applied, the duration range over which the treatment protocol is applicable, the particular features of interest within the target region that are visible, etc. In this way, decision 306 effectively determines whether the target region is present within imaging beam 160 (substantially or completely coincident with treatment beam 162) sufficiently to activate treatment beam 162 and perform a treatment session.

[0064] Referring to various real-world scenarios that may provide further context for such an approach, the spleen and liver are two illustrative examples. With respect to the spleen, the effects of targeted ultrasound-based therapy are generally uniform across the spleen tissue, and accordingly, a lower percentage of visibility (e.g., 50%) may be acceptable and still achieve the desired therapeutic effect. However, to target the spleen, the transducer is typically positioned between the ribs, which may inadvertently fall within the beam path. Furthermore, the pancreas is located close to the spleen, which may result in inadvertent overlap between targeted and non-targeted tissue. Correspondingly, for spleen-based therapy, a higher percentage of safety criteria (e.g., 90%) may be adopted, along with an acceptable lower visibility.

[0065] Conversely, in the liver, the effects of ultrasound therapy are nonhomogeneous across liver tissue. That is, to achieve the desired therapeutic effect, it may be necessary to target specific regions, subregions, or anatomical structures of the liver (e.g., the porta hepatis). As a result, in contrast to the spleen example, a higher percentage of visibility (e.g., 75%) may be specified to achieve the desired therapeutic effect. Furthermore, in contrast to the spleen example, liver access is epigastric (i.e., the transducer may be placed on the skin in the soft tissue of the abdomen below the rib cage), avoiding bone, and off-target energy primarily lands on other lobes of the liver where there is little therapeutic effect, so a lower safety standard may be acceptable. This may allow for a lower or even lower safety standard (e.g., 75% safety standard). Although this lowering of safety standards does not necessarily mean that there are no safety concerns (due to the proximity of the stomach and intestines to the liver), taking into account the expected beam path (i.e., the position of the probe in the abdomen and the anatomical structure of the liver), safety concerns may be somewhat alleviated.

[0066] If the region of interest is not present (or is not sufficiently present) in the imaged region, a remediating action 320 may be performed. Such a remediating action 320 may include providing a notification to a user (e.g., a patient, in certain examples) to reposition and / or reorient the probe structure 42. In response to the notification, the user may translate and / or tilt the probe head until a path is determined to exist that includes the target region and is otherwise determined to be suitable. Alternatively, the remediating action may be performed automatically by the system to electronically adapt the performance of the probe (e.g., electronically sweeping the imaging beam and / or therapy beam to find a path to the target region, internally moving transducer elements (in a dynamic transducer configuration as discussed herein) to find a path, or otherwise automatically adjusting the position and / or operating parameters of the transducer 50 as discussed herein to achieve a path). For example, to the extent that electronic beam steering is possible in the probe 42, the probe 42 can automatically sweep the scannable area using embedded electronic motion control in an attempt to identify target areas and / or satisfy path evaluation criteria.

[0067] If it is determined that a path exists from the probe 42 to the target region, a further determination 330 may be made to ascertain whether other relevant factors or conditions are met for the path under evaluation. By way of example, factors related to safety criteria 334, treatment dose 336, and treatment effect 338 for the path under evaluation may be considered as part of the determination 330. If it is determined that one or more of these factors mean that the treatment beam should not be applied, corrective action 320 is taken, as described above.

[0068] In certain embodiments, the determination 330 can be based in whole or in part on an analysis of the image data 302. The image data 302 may be analyzed using traditional approaches or through machine learning or artificial intelligence approaches. Such analysis may include identifying image or image data regions indicative of structures or regions with relatively high or low density relative to soft tissue (e.g., bone, cartilage, gas-filled cavities) that are present in the path to the target region. Such structures may be associated with acoustic absorption or reflection (e.g., shadowing) of ultrasound energy in both image analysis and treatment delivery. The adequacy of acoustic coupling between the patient and the probe structure 42 may also be a factor in the determination 330, with poor acoustic coupling being determined based on regions or areas in the image data 302 that are excessively blurred or dim relative to image data acquired under conditions of sufficient acoustic coupling. Analysis of the image data 302 may also be performed to determine a “lift-off” condition, which may be indicated by a missing or dim image along the edge of the image data when a portion (e.g., the end) of the probe 42 is not pressed against the patient's skin.

[0069] If it is determined in decision block 330 that the treatment beam 162 can be applied, the transducers 50 (e.g., one or more treatment transducers 52) may be activated to apply the treatment beam 162 targeted to the target region (step 340). The treatment beam 162 may be applied to the target region for a time interval. Once it is determined (decision block 344) that the treatment session is complete (e.g., the prescribed therapy dose has accumulated at the target region), the treatment beam 162 may be turned off, terminating treatment (step 346). Conversely, if treatment is not complete after a set time has elapsed, path evaluation and transducer alignment may be repeated (e.g., after repositioning the probe 42) until treatment is complete. Also, while one order of steps is depicted with respect to FIG. 18 , it should be understood that in practice, the particular order of steps may be performed in a different order.

[0070] In a further aspect of the present technology, therapy transducers and control schemes may be employed that enable selective activation and deactivation of respective subsets of therapy transducers 54 based on the results of the pathway analysis or evaluation. As an example, a subset of therapy transducers 54 that have clear pathways to the target region may be selected for activation based on the pathway analysis, while a correspondingly different subset of therapy transducers 54 that lack clear pathways based on the pathway analysis may be selectively deactivated for a given therapy delivery. In such an embodiment, with respect to the process flow shown in FIG. 18 , the pathway analysis decision at one or both of decision blocks 306 and 330 may be qualified or partial, i.e., a clear pathway may be determined to exist for some, but not all, of the therapy transducers 54. In this embodiment, instead of requiring the user to reposition and / or reorient the probe, a threshold amount or percentage (e.g., 50%, 75%, 85%, 95%, etc.) of the therapy transducers 54 may be determined to have a clear path, and therapy may be delivered by activating only those therapy transducers 54 that have a clear path. Furthermore, in such a scenario, a computer-implemented routine or control scheme may be employed to dynamically adjust the intensity and / or duration of a subset of activated therapy transducers 54 to optimize therapy delivery for a given position and / or orientation of the probe 42. In such circumstances, dynamic adjustments made to the activation and / or operating parameters of the therapy transducers 54 may reduce or eliminate repositioning and / or reorientation of the probe 42.

[0071] As discussed herein, in practice, certain of these considerations may also utilize sensor data 360 (step 362) acquired using one or more sensors 70, such as electrodes, cavitation sensors, pressure sensors, etc., located inside or outside the probe 42. Such sensor data 360 may be utilized in addition to, or in place of, the image data 302 to evaluate certain factors that may be considered in determining whether to proceed with treatment beam application. Furthermore, in some implementations, signals generated by individual elements of the therapy transducer array (i.e., the therapy transducers 54) may be used as part of path determination, such as to identify large reflections or other signatures in the echoes that indicate blocking anatomy, to determine the sufficiency of acoustic coupling, etc. In the depicted example, the sensor data 360 may be used in addition to, or in place of, the image data 302 to determine whether a probe head “lift-off” event has occurred (step 364), the result of which may be a factor considered in decision block 330. Similarly, the same or different sensor data 360 can be used in addition to or instead of the image data 302 to determine the sufficiency of acoustic coupling between the probe head and the patient (step 366), the results of which can be factors considered in decision block 330.

[0072] The preceding discussion relates to various devices, transducer configurations, and methodologies and steps that can be utilized to analyze or evaluate a treatment beam path in a patient treatment context and use such determinations to safely deliver a predetermined ultrasound dosage to a patient's target area. Indeed, the use of path evaluation techniques as discussed herein may enable the safe application of ultrasound therapy by individuals with little medical training, or even the patient themselves, who are not trained to apply such dosages. By ensuring a clear path for the point of incidence and the propagation path of the treatment beam 162, detrimental transducer design constraints (e.g., coherent imaging and treatment frequency, which would compromise imaging and treatment performance) need not be imposed. Also, visualization of the treatment beam quantifies treatment delivery, eliminating the need for sophisticated controls and algorithms to mitigate image corruption while simultaneously imaging and delivering treatment. These advantages enable low-cost systems for imaging and therapy.

[0073] Furthermore, with regard to alternatives, for other approaches to provide equivalent functionality, they would need to quantify the treatment beam in the target region by some means other than those described herein. In strictly ultrasound-based systems, this would likely involve visualizing the treatment beam in an image or other advanced signal processing techniques to measure the actual ultrasound energy deep within the body. The present approach works without the need for such visualization or measurement.

[0074] In particular, while quantifying the true dose may be attractive, this is difficult in practice and entails additional requirements that can render many aspects of imaging / therapy systems difficult, bulky, and expensive. For example, coherent imaging and therapy frequencies are sometimes employed to visualize the beam. In this case, a compromise is required: the imaging frequency is lower than the desired frequency (reducing resolution) and the therapy frequency is higher than the desired frequency (leading to greater attenuation and reduced treatment power to levels that may be ineffective). As a result, this approach results in suboptimal imaging and therapy performance, necessitating the development of new broadband transducer materials. Furthermore, to visualize the treatment beam, imaging and therapeutic ultrasound signals are applied simultaneously. In this arrangement, the therapeutic ultrasound signal distorts the image, making target localization difficult. Furthermore, if other advanced signal processing techniques were to be used instead, very high image resolution would be required, necessitating the use of complex systems similar to large console systems. In contrast to current approaches, such systems are impractical for home use or use by untrained individuals.

[0075] The disclosed technology allows delivery of ultrasound therapeutic energy (e.g., neuromodulation energy) to a target region in conjunction with a clear path determination that evaluates one or more of: (1) the presence of non-soft tissue regions (e.g., bone or bone-like structures, gas-filled cavities, etc.) in the treatment beam path, (2) partial "lift-off" of the probe head, or (3) sufficiency of acoustic coupling. Once a clear path is determined or confirmed with respect to some or all of these factors, the treatment beam is emitted to the target region.

[0076] This specification 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 the incorporated 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 be 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 that do not differ substantially from the literal language of the claims. [Explanation of symbols]

[0077] 10: Neuroregulatory system 12: Energy application device 14: Pulse generator 16: Controller 20: Evaluation device 40: Treatment Module 42: Probe module 44: Imaging module 50: Transducer 52: Imaging transducer 54: Therapeutic transducer 56: Focal Spot 60, 126: HW controller 62, 122: MCU 64, 124: FPGA 70: Sensor 80: Any actuator 82: Motor 1 84: Motor 2 86: Patient-specific manual adjustment 110: Master controller 112: Image streamer and remote control 114: AI Anatomical Recognition and Tracking 116: Induction dosing engine 118: User Interface 120: Support Analysis 122: Data logger 130: Therapeutic Pulser Receiver 132:Safety circuit 134: Power management circuit 150: Cap 152: Internal standoff 160: Imaging beam 162: Treatment beam 180: Acoustic window 182: Pendulum arm 184: Linear motion arm 186, 188: Movement arrows 200: skin

Claims

1. 1. An ultrasound therapy delivery system comprising: an energy application device configured to deliver ultrasound energy to a target region of a subject, the energy application device including one or more transducers configured to emit an imaging beam and a treatment beam, and a controller; The controller: activating some or all of the one or more transducers to emit an imaging beam; receiving image data generated in response to the imaging beam; determining whether all or a portion of the target area is present in the image data scanned by the imaging beam; in response to identifying at least a portion of the target area in the image data, determining whether the treatment beam can be applied to the target area to provide all or a portion of a therapeutic dose of ultrasound energy to the target area; in response to determining that the therapeutic beam can be emitted to the target area to provide the therapeutic dose, actuating some or all of the one or more transducers to emit the therapeutic beam and provide all or a portion of the therapeutic dose to the target area; 23. An ultrasound therapy delivery system configured to perform actions including:

2. The energy application device further comprises: an acoustically transparent cap configured to contact a skin surface of the subject; a standoff region between the sound-transmissive cap and at least a portion of the one or more transducers; 10. The ultrasound therapy delivery system of claim 1, comprising:

3. Determining whether the treatment beam can be applied to the target area to provide all or a portion of the therapeutic dose comprises: Identifying, within the image data, one or both of interfering or off-target anatomical regions within a treatment beam path; determining whether one or both of a therapeutic dose criterion or an off-target safety criterion are met by the treatment beam path based on the presence of the obstructing anatomical region or the off-target anatomical region; 10. The ultrasound therapy delivery system of claim 1, comprising:

4. 2. The ultrasound therapy delivery system of claim 1, wherein activating some or all of the one or more transducers to emit the treatment beam comprises activating a subset of the one or more transducers based on identification in the image data of interfering or off-target anatomical regions.

5. 2. The ultrasound therapy delivery system of claim 1, wherein determining whether the treatment beam can be applied to the target area to provide all or a portion of the therapeutic dose comprises comparing the portion of the target area modulated by the treatment beam to an efficacy threshold.

6. 10. The ultrasound therapy delivery system of claim 1, further comprising one or more sensors configured to generate sensor data, the one or more sensors comprising one or both of an electrode, a pressure sensor, or a passive cavitation detection sensor.

7. 7. The ultrasound therapy delivery system of claim 6, wherein determining whether the treatment beam can be applied to the target area to provide all or a portion of the therapeutic dose includes using the image data or the sensor data to determine that acoustic coupling of the energy application device to the subject is sufficient.

8. 8. The ultrasound therapy delivery system of claim 7, wherein activating some or all of the one or more transducers comprises activating a subset of the one or more transducers based on sufficiency of the acoustic coupling of the energy application device to the subject.

9. 7. The ultrasound therapy delivery system of claim 6, wherein determining whether the treatment beam can be applied to the target area to provide all or a portion of the therapeutic dose includes determining whether or not there is a lift-off event of the energy application device relative to a subject using the image data or the sensor data.

10. 10. The ultrasound therapy delivery system of claim 9, wherein activating some or all of the one or more transducers comprises activating a subset of the one or more transducers based on the presence of a lift-off event of the energy application device relative to the subject.

11. 2. The ultrasound therapy delivery system of claim 1, wherein the one or more transducers include one or more therapy transducers configured to emit the therapy beam and one or more imaging transducers configured to emit an imaging beam that scans at least a portion of a path that the therapy beam takes to the target area.

12. 12. The ultrasound therapy delivery system of claim 11, wherein the one or more therapy transducers emit the therapy beam within a first frequency range and the one or more imaging transducers emit the imaging beam within a second frequency range that is higher than the first frequency range.

13. The ultrasound therapy delivery system of claim 1 , wherein the imaging beam and the therapy beam are emitted at the same frequency.

14. The controller further comprises: generating a notification or message to perform one or more of: repositioning or reorienting the energy application device in response to determining that a sufficient portion of the target area is not present in the image data or that the treatment beam cannot be applied to the target area to provide the therapeutic dose; and repeating a determination that the target region is present in the image data and a determination that the treatment beam can be delivered to the target region until both determinations are positive, and then activating some or all of the one or more transducers to deliver the treatment beam; The ultrasound therapy delivery system of claim 1 , configured to perform the operations of:

15. The controller further comprises: automatically adjusting one or both of a position or orientation of the one or more transducers in response to determining that a sufficient portion of the target region is not present in the image data or that the treatment beam cannot be applied to the target region to provide the therapeutic dose; repeating a determination that the target region is present in the image data and a determination that the treatment beam can be delivered to the target region until both determinations are positive, and then activating some or all of the one or more transducers to deliver the treatment beam; The ultrasound therapy delivery system of claim 1 , configured to perform the operations of:

16. The ultrasound therapy delivery system of claim 2 , wherein the imaging beam completely encompasses the extent of the treatment beam in at least one dimension beyond the sonolucent cap.

17. 10. The ultrasound therapy delivery system of claim 1, wherein activating some or all of the one or more transducers to emit the treatment beam comprises one or both of selectively activating multiple transducers or adjusting operating parameters.

18. 1. A method for delivering ultrasound therapeutic energy, comprising: acquiring image data of a subject using an ultrasound imaging beam; determining whether all or a portion of a treatment target region is present in the image data; in response to determining that at least a portion of the target region is present in the image data, determining whether an ultrasound treatment beam can be applied to the target region to provide all or a portion of a therapeutic dose of ultrasound energy to the target region, the path of the ultrasound treatment beam at least partially overlapping a path of the ultrasound imaging beam within the subject; in response to determining that the ultrasound treatment beam can be applied to the target area to provide the therapeutic dose, actuating one or more transducers to emit the ultrasound treatment beam and provide all or a portion of the therapeutic dose to the target area of ​​the subject.

19. Determining whether the treatment beam can be applied to the target area to provide all or a portion of the therapeutic dose comprises: Identifying, within the image data, one or both of interfering or off-target anatomical regions within the path of the ultrasound therapy beam; determining whether one or both of a therapeutic dose criterion or an off-target safety criterion are met by the treatment beam path based on the presence of the obstructing anatomical region or the off-target anatomical region; 20. The method of claim 18, comprising:

20. 20. The method of claim 18, wherein activating the one or more transducers to emit the ultrasound treatment beam comprises activating a subset of a plurality of transducers based on identification in the image data of interfering or off-target anatomical regions that are in a treatment beam path.

21. 20. The method of claim 18, wherein determining whether the treatment beam can be applied to the target area to provide all or a portion of the therapeutic dose comprises comparing the portion of the target area modulated by the treatment beam to an efficacy threshold.

22. 20. The method of claim 18, wherein activating some or all of the one or more transducers comprises activating a subset of a plurality of transducers based on sufficiency of the acoustic coupling of the energy application apparatus to the subject.

23. 20. The method of claim 18, wherein activating the one or more transducers to emit the ultrasound treatment beam comprises activating a subset of a plurality of transducers based on the presence of a lift-off event of the energy application device relative to the subject.

24. Activating the one or more transducers to emit the ultrasound treatment beam comprises: one or more therapy transducers configured to emit the ultrasound therapy beam; 20. The method of claim 18, comprising activating a subset of a plurality of transducers, one or more imaging transducers configured to emit the ultrasound imaging beam, the ultrasound imaging beam scanning at least a portion of a path traversed by the ultrasound therapy beam to the target area.

25. generating a notification or message to perform one or more of: repositioning or reorienting the energy application device in response to determining that a sufficient portion of the target area is not present in the image data or that the ultrasound treatment beam cannot be directed to the target area to provide the therapeutic dose; 20. The method of claim 18, further comprising: repeating the steps of determining that the target region is present in the image data and determining that the ultrasound treatment beam can be applied to the target region until both determinations are positive, and activating the one or more transducers to apply the ultrasound treatment beam.

26. automatically adjusting one or both of a position or orientation of the one or more transducers in response to determining that a sufficient portion of the target area is not present in the image data or that the ultrasound treatment beam cannot be directed to the target area to provide the therapeutic dose; 20. The method of claim 18, further comprising: repeating the steps of determining that the target region is present in the image data and determining that the ultrasound treatment beam can be applied to the target region until both determinations result in positive results, and then activating some or all of the one or more transducers to emit the ultrasound treatment beam.

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