Standoff for targeted ultrasound therapy

Abstract

To provide a target ultrasonic therapy standoff.SOLUTION: Embodiments of the present disclosure relate to gel standoffs for use with an ultrasound probe and compositions and techniques for making and using the same. The composition and properties of the gel standoffs can be customized to accommodate the clinical needs of the subject and / or the treatment protocol utilizing the ultrasound probe. In certain embodiments, the gel standoff may be designed to treat a subject via neuromodulation.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] The subject matter disclosed herein relates to the application of ultrasound energy. One example of the subject matter disclosed herein relates to identifying, targeting, and / or administering energy (e.g., neuromodulating ultrasound energy) to a region of interest in a subject to induce a targeted physiological result. In particular, one example of the disclosed technology can be useful for facilitating precise delivery of a therapeutic dose of ultrasound energy to a targeted region. [Background technology]

[0002] Ultrasound-based neuromodulation has been used to treat a variety of clinical conditions. However, targeting specific tissues for neuromodulation can be challenging. A particular patient may have variations in organ size and location relative to other patients based on height, weight, age, sex, clinical condition, etc., and these variations can affect targeting and dose delivery when using various neuromodulation techniques.

[0003] In the context of neuromodulation using ultrasonic devices, other common challenges in delivering an accurate prescribed dose of ultrasound treatment include poor acoustic coupling between the treatment probe and the patient, "lift-off" of portions of the probe from the patient, poor image quality, 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. Summary of the Invention

[0004] Various refinements of the features described above may exist in connection with various aspects of the present disclosure. Additional features may also be incorporated into these various aspects as well. These refinements and additional features may exist individually or in any combination. For example, various features described below in connection with one or more of the illustrated embodiments may be incorporated alone or in any combination into any of the above-described aspects of the present disclosure. The brief summary presented above is intended only to familiarize the reader with certain aspects and context of embodiments of the present disclosure without limitation to the claimed subject matter.

[0005] In one embodiment, a gel standoff is provided. According to this embodiment, the gel standoff comprises a gel standoff body including a moldable material. The gel standoff also comprises one or more mating features formed within the gel standoff body. The one or more mating features are configured to fit over one or more structural features of the ultrasound probe. The gel standoff further comprises a patient-facing surface. The patient-facing surface is configured to contact the patient's skin during use.

[0006] In one embodiment, a method for attaching gel standoffs to an ultrasound probe is provided. According to the method, a lid of a gel pad pack is removed. The gel pad pack is opened to expose gel standoffs within the gel pad pack. The gel pad pack is aligned with an ultrasound probe. One or more mating portions of the gel standoffs are aligned when aligned with complementary mating portions of the ultrasound probe. The gel standoffs of the gel pad pack are pressed against the ultrasound probe. In response to the pressure, the gel standoffs are pulled away from the gel pad pack and engage with the ultrasound probe. The ultrasound probe with the engaged gel standoffs is separated from the gel pad pack.

[0007] In one embodiment, a method for using a gel standoff is provided. According to the method, the gel standoff is inserted into a complementary cavity in an ultrasound probe. The ultrasound probe is pressed against a subject. Energy is applied through the gel standoff and directed to a region of interest in the subject to induce neuromodulation. Once energy application is complete, the gel standoff is removed from the ultrasound probe. [Brief explanation of the drawings]

[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. [Figure 1] FIG. 1 is a schematic diagram of a neuromodulation system according to an embodiment of the present disclosure. [Figure 2] FIG. 1 is a block diagram of a neuromodulation system according to an embodiment of the present disclosure. [Figure 3] FIG. 10 is a schematic diagram of a transducer arrangement with gel standoffs used for clear-path determination, according to an embodiment of the present disclosure. [Figure 4A] FIG. 1 is a schematic diagram of a patient-facing portion of an ultrasound probe having gel standoffs in accordance with an embodiment of the present disclosure. [Figure 4B] FIG. 1 is a schematic diagram of the patient-facing portion of an ultrasound probe with a standard cap arrangement. [Figure 5] FIG. 1 is a schematic diagram of a mold for manufacturing gel standoffs, according to an embodiment of the present disclosure. [Figure 6] 1 shows a schematic diagram of a patient-facing portion of an ultrasound probe having a gel standoff arrangement used with an example of a gel standoff according to an embodiment of the present disclosure. [Figure 7] 1 shows a schematic diagram of a patient-facing portion of an ultrasound probe having a gel standoff arrangement used with an example of a gel standoff having a complex structure, according to an embodiment of the present disclosure. [Figure 8] FIG. 1 is a schematic diagram of a gel standoff housed in a container, according to an embodiment of the present disclosure. [Figure 9]1 is an exemplary workflow of one method for attaching gel standoffs to an ultrasound probe, according to an embodiment of the present disclosure. [Figure 10A] 1A-1C schematically illustrate three exemplary methods for removing gel standoffs from an ultrasound probe, according to embodiments of the present disclosure. [Figure 10B] 1A-1C schematically illustrate three exemplary methods for removing gel standoffs from an ultrasound probe, according to embodiments of the present disclosure. [Figure 10C] 1A-1C schematically illustrate three exemplary methods for removing gel standoffs from an ultrasound probe, according to embodiments of the present disclosure. [Figure 11] 1A-1C are schematic diagrams of alternative compositions of gel standoffs according to embodiments of the present disclosure. [Figure 12] 10 is a comparison of ultrasound image quality acquired with a standard cap arrangement versus gel standoffs, according to an embodiment of the present disclosure. [Figure 13] 1 is a schematic diagram of a gel standoff with increased thickness according to an embodiment of the present disclosure. FIG. [Figure 14] 1 is a schematic diagram of angled gel standoffs according to an embodiment of the present disclosure. [Figure 15] FIG. 10 is a schematic diagram of a custom molded gel standoff for a patient, according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0009] 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 in the specification. It should be understood that the development of such an actual implementation, as with any engineering or design project, will involve numerous implementation-specific decisions to achieve the developer's particular goals, including compliance with system-related and business-related constraints. These constraints may vary from implementation to implementation. 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.

[0010] The examples or illustrations provided herein are not to be construed as limiting, restricting, or expressly defining any terms or terms in which they are used. Instead, these examples or illustrations are described in terms of various specific embodiments and are to be considered illustrative only. Those skilled in the art will understand that any term or term used in these examples or illustrations 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, "for example," "for example," "exemplary," "including," "particular embodiments," "some embodiments," and "in one embodiment." All numerical values ​​in the detailed description herein are modified by the indicated value "about" to account for experimental error and variation expected by one of ordinary skill in the art. For example, "about" or "approximately" may refer to ±0.5%, ±1%, ±2%, ±5%, ±10%, or ±15%.

[0011] When introducing elements of various embodiments of the disclosure, the articles "a," "an," "the," and "said" are intended to mean that there are one or more of the elements. The terms "comprising," "including," and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements. Furthermore, any numerical examples in the following discussion are intended to be non-limiting, and therefore, additional numerical values, ranges, and percentages are within the scope of the disclosed embodiments.

[0012] The term "gel standoff" (e.g., hydrogel standoff) is used herein to describe a non-liquid, non-gaseous standoff that may be conformable or moldable to fit within the internal cavity of an ultrasound probe and / or to fit against a patient's skin. Furthermore, it should be noted that the composition of a "gel standoff" is not limited to gel. Thus, as described herein, "gel" can refer to hydrogels, waxes, polymers, solid oils, and other moldable and / or conformable materials.

[0013] Ultrasound-based neuromodulation has been used to treat a variety of clinical conditions, including metabolic disorders such as diabetes or hyperglycemia, inflammatory or immune disorders, and others. In practice, ultrasound-based neuromodulation is sometimes implemented as image-guided ultrasound therapy, and such applications can utilize a variety of transducer imaging / treatment configurations. For example, an ultrasound probe can include a central imaging transducer and a separate outer ring treatment transducer. Such configurations are often used for high-intensity focused ultrasound (HIFU) treatments, but are also relevant for neuromodulation when utilizing higher power levels than conventional imaging. The separate imaging and treatment transducers are optimized for their respective purposes and are often interleaved in time, with the imaging transducer used to identify internal anatomical targets and then (i.e., switched) delivering an ultrasound dose to the target using the treatment transducer. In most situations, the imaging and treatment transducers are mounted concentrically or adjacently, using separate lenses or co-molded lenses (or fluid-filled caps) on both transducers, and standard ultrasound coupling gels can be used in conjunction. For example, adjacently mounted transducer configurations may use treatment transducers with concave shapes that utilize ultrasound coupling gel to fill the concave cavity during application, resulting in messy application and an overall poor user experience. Furthermore, this arrangement typically does not allow for determining whether a “clear path” exists for the treatment beam to propagate from the ultrasound probe to the target area and beyond. Determining such a clear path for the treatment beam generally depends on various factors (e.g., absence of bone or bone-like structures, presence or absence of gas-filled pockets or cavities, good acoustic coupling, lack of probe head “lift-off” from the patient surface) and is useful for providing accurate administration and patient safety. Thus, certain fluid-filled cap configurations and shapes may be useful for enabling clear path determination, but may have the unintended consequence of degrading image quality.

[0014] For example, 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 correspond to areas of the patient that are traversed by the treatment beam but are not observed (e.g., seen) by the imaging technique. As used herein, the path of the treatment beam (i.e., the treatment beam path) encompasses objects or structures near the target region as well as the region from the target region "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 respect 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 being "off-target" (i.e., affecting or applying energy to patient regions that are not part of the target region) and / or not delivering 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 seen by the imaging arrays but may be traversed by the treatment beam. Such blind spots are problematic in image-guided therapy.

[0015] In this regard, additional challenges in providing accurate and safe ultrasound treatment using image-guided techniques may 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 (e.g., bony structures such as ribs, gas-filled pockets or areas such as intestinal gas) in the treatment beam path. 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") may occur when the transducer is over a shadow-causing structure (e.g., ribs). Such factors may present inaccurate dose delivery, patient safety hazards (e.g., burns, cavitation), and / or patient discomfort.

[0016] Importantly, ultrasonic pressure waves create mechanical forces that are applied to internal tissues. If the mechanical forces become too large, undesirable mechanical bioeffects can occur. Furthermore, ultrasound beams can cause internal tissue heating while the tissue absorbs the ultrasound energy. Internal heating can increase with factors such as increased power and effective duty cycle. If internal heating becomes too large, many undesirable thermal bioeffects can occur. Furthermore, tissue attenuation and acoustic impedance vary depending on the tissue type. 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, while 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, cavitation can occur, potentially affecting surrounding tissues.

[0017] Due to the above-mentioned issues and the need to ensure accurate dose delivery (and thus effective treatment), it may be desirable to be able to steer and / or focus the ultrasound beam without repositioning or reorienting the probe head in contact with the patient. Furthermore, the contact between the probe head and the patient must be conducive to the propagation of the ultrasound beam, as well as mechanical and / or electronic steering and focusing techniques. Therefore, determining the path adjustment and / or path analysis may involve a number of 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.), some of which may be considered in a given path determination. The types of factors considered may depend on considerations such as the treatment protocol, patient anatomy, system geometry, and the desired frequency and / or dose.

[0018] With this in mind, the techniques and approaches discussed herein comprise a combination of physical embodiments and implementations that can be employed to provide safe and precise delivery of therapy to a target. While the presently described techniques and approaches are useful for trained technicians to administer ultrasound therapy treatments to target areas on a patient, these techniques and approaches can also be employed to enable non-medically trained individuals, including the patient themselves, to safely administer ultrasound therapy treatments while achieving the desired medical effect without risk of injury.

[0019] The gel pad standoffs (e.g., gel pads, gel pad inserts, gel standoffs) provided herein are designed for use with ultrasound therapy configurations with multiple transducer designs (e.g., one-transducer, two-transducer, three-transducer, or more) to ensure a clear path for therapy delivery and high image quality in an imaging or targeting context, allowing for easy user workflow and minimal or no post-treatment cleanup. The gel standoffs help ensure patient safety in ultrasound therapy procedures by minimizing and / or eliminating decoupling, lift-off, and / or facilitating mechanical or electronic steering (e.g., to avoid or avoid acoustic reflectors or absorbers in the treatment beam path (i.e., bone / ribs, intestinal gas)). Thus, the gel standoffs are configured to allow acoustic energy to pass from the transducer of an ultrasound probe to the contacted patient surface, used to provide a therapeutic effect and / or for imaging. The gel standoffs described herein offer substantial advantages over commonly employed hard-shell fluid-filled caps. For example, the use of gel standoffs improves image quality (e.g., better acoustic impedance matching and reduced reverberation compared to hard-shell caps), eliminates the need for internal oil / liquids, and thereby simplifies the overall probe design, reduces costs, and eliminates the need for ultrasound gel to improve patient experience / workflow.

[0020] Additional features are presented that tailor the shape of the gel pad to fit a patient's unique shape. For example, the gel standoff shape can be custom molded to fit the internal cavity of a two-transducer ultrasound probe geometry for acoustic coupling. The gel pad, in some embodiments, can exhibit snap-in features (e.g., grooves and corresponding ridges on the probe) to enable hands-free press insertion. In some embodiments, the shape of the gel standoff can be modified to fit the patient's anatomy at the probe placement location (e.g., region of interest). In this way, the gel standoff can be custom-fit to a specific patient or use case (e.g., target anatomy (i.e., region of interest), target depth), thereby improving comfort, stability, and acoustic coupling.

[0021] Additionally, gel standoffs can be tailored to have material compositions with specific acoustic properties to enable more effective treatment delivery. For example, gel standoffs can be tailored or constructed to have specific material compositions or combinations of compositions, such as multi-material compositions. In some embodiments, multi-material compositions can include lens-like structures embedded or otherwise formed within the gel standoff to adjust the angle of the ultrasound beam toward the region of interest. Furthermore, the material composition of the gel standoff can be selected or tailored to change the attenuation, speed of sound, or acoustic impedance of the medium to achieve desired beam characteristics, enhance coupling, exhibit "wetness" for long-term use, or aid in focusing the treatment beam onto the target. For example, an attenuation of approximately 5 decibels per centimeter per megahertz (dB / cm / MHz) may be undesirable in certain areas (e.g., bone has an attenuation of approximately 3.54 dB / cm / MHz). Thus, in certain embodiments, the gel standoff can have an attenuation of 0.1 dB / cm / MHz or less. In other embodiments, the gel standoffs may be configured to have an attenuation between 0.1 dB / cm / MHz and 5 dB / cm / MHz to approximate tissue attenuation. Similarly, in certain embodiments, the acoustic impedance of the gel standoffs may be within the relevant acoustic impedance range of tissue, such as between 1 mega array (MRayl) and 6 mega arrays, at the frequencies generated by the corresponding ultrasound probe to which the gel standoffs may be attached. Phase change gel pad materials (e.g., phase changing materials), activation methods, and related advantages are also described herein. Thus, gel standoffs can significantly improve image quality compared to fluid-filled caps, while providing comparable or superior ultrasound therapy and imaging capabilities.

[0022] With the above in mind, FIG. 1 is a schematic diagram of a system 10 for neuromodulation. Such a neuromodulation system 10 can be used to achieve neurotransmitter release and / or activation of synaptic components (e.g., the presynaptic cell, the postsynaptic cell) in response to the application of ultrasound 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 energy pulses, e.g., via a lead or wireless connection, that, during use, are directed to a region of interest in a subject's internal tissue or organ, resulting in local and / or systemic changes in the concentration of a biologically active molecule, process, or function, such as changes to the concentration of a glucose transporter pathway molecule and / or an incretin pathway molecule in the context of a metabolic disorder treatment.

[0023] In certain embodiments, the energy application device 12 and / or the pulse generator 14 can be in wireless communication with, for example, a controller 16, which can in turn provide instructions to the pulse generator 14. In other embodiments, the pulse generator 14 can be an extracorporeal device, e.g., operable to apply energy transcutaneously or non-invasively from a location outside the subject's body, and in certain embodiments, can be integrated into the controller 16. In embodiments in which the pulse generator 14 is extracorporeal, the energy application device 12 can be operated by a caregiver and positioned at or above the subject's skin to deliver energy pulses transcutaneously to desired internal tissues. Once positioned to apply energy pulses to desired sites, the system 10 can initiate neuromodulation of one or more target internal sites to achieve a clinical effect, such as treatment of a metabolic disorder.

[0024] In certain embodiments, system 10 may include an evaluation device 18 coupled to controller 16 that evaluates a characteristic indicative of whether a change in a patient characteristic of interest, such as a change in glucose transporter pathway molecules and / or incretin pathway molecules, has been achieved as a result of neuromodulation. In one embodiment, the characteristic may be local. For example, modulation may result in a local tissue or functional change, such as a change in tissue structure, a local change in the concentration of a particular molecule, tissue displacement, increased fluid movement, etc.

[0025] Modulation may additionally or alternatively result in systemic or non-local changes, and the targeted physiological outcome may be related to changes in the concentration of circulating molecules or changes in tissue properties that do not include the region of interest to which energy is directly applied. In one example, the displacement may be a proxy measurement for a desired modulation, and a displacement measurement below an expected displacement value may result in modulation of the modulation parameters until the expected displacement value is induced. Thus, in some embodiments, the evaluation device 18 may be configured to evaluate a molecule or molecule concentration change of interest. In some embodiments, the evaluation device 18 may be an imaging device configured to evaluate changes in organ size and / or position. While the depicted elements of the system 10 are shown separately, it should be understood that some or all of the elements may be combined with each other. Furthermore, some or all of the elements may be in wired or wireless communication with each other.

[0026] Based on the evaluation, modulation parameters of the controller 16 can be altered. For example, if the desired modulation is within a defined time window (e.g., 5 minutes, 30 minutes after the start of the energy application procedure), or compared to a baseline measurement at or before the start of the procedure, a change in modulation parameters, such as pulse frequency, may be desired, which may be provided to the controller 16 by an operator or via an automatic feedback loop to define or adjust the energy application or modulation parameters of the pulse generator 14.

[0027] The system 10 provided herein can provide energy pulses according to various modulation parameters. For example, modulation parameters can include various stimulation time patterns, ranging from continuous to intermittent. In intermittent stimulation, energy is delivered at a frequency for a fixed duration during a signal-on time. The signal-on time is followed by a period during which no energy is delivered, referred to as a signal-off time. Modulation parameters also include the frequency and duration of stimulation application. The application frequency can be continuous or can be delivered over various time periods, e.g., within a day or a week. Treatment duration can last for various durations, including, but not limited to, from several minutes to several hours. In certain embodiments, treatment duration with a particular stimulation pattern can last for one hour, repeated at 72-hour intervals, for example. In certain embodiments, treatment can be provided more frequently, e.g., every three hours, for a shorter duration, e.g., 30 minutes. The application of energy according to modulation parameters, such as treatment duration and frequency, can be adjustably controlled to achieve desired results.

[0028] 2 is a block diagram of certain components of system 10. As provided herein, system 10 for neuromodulation can include a pulse generator 14 adapted to generate a plurality of energy pulses for application to tissue of a subject. Pulse generator 14 can be separate or integrated into an external device, such as controller 16. Controller 16 includes a processor 20 for controlling the device. Software code or instructions are stored in memory 22 of controller 16 for execution by processor 20 to control various components of the device. Controller 16 and / or pulse generator 14 can be connected to energy application device 12 via one or more leads 33 or wirelessly.

[0029] The controller 16 also includes a user interface having input / output (I / O) circuitry 24 and a display 26 adapted to allow a clinician to provide selection inputs or modulation parameters for the modulation programs. Each modulation program can include one or more sets of modulation parameters, including pulse amplitude, pulse width, pulse frequency, etc. The pulse generator 14 modifies its internal parameters in response to control signals from the controller 16 to vary the stimulation characteristics of the energy pulses delivered to the subject via the leads 28 by the energy application device 12. Any suitable type of pulse generation circuit can be employed, including, but not limited to, constant current, constant voltage, multiple independent current or voltage sources, etc. The applied energy is a function of current amplitude and pulse width duration. By modifying the modulation parameters, the control device 16 can adjustably control the energy and / or initiate or cancel / suppress energy application at specific times. In one embodiment, the adjustable control of the energy application device is based on information regarding the concentration of one or more molecules (e.g., circulating molecules) within the subject. If the information is from the evaluation device 18, a feedback loop can drive the adjustable control. For example, if circulating glucose concentrations in blood or urine measured by evaluation device 18 exceed a predetermined threshold or range, controller 16 may initiate energy application to a region of interest (e.g., the liver) using modulation parameters associated with a decrease in circulating glucose. Initiation of energy application may be triggered by glucose concentrations exceeding a predetermined (e.g., desired) threshold or drifting outside a predetermined range. In another embodiment, adjustable control may be in the form of altering modulation parameters if the initial application of energy does not result in an expected change in a targeted physiological outcome (e.g., concentration of a molecule of interest) within a predefined time frame (e.g., 1 hour, 2 hours, 4 hours, 1 day).

[0030] In one embodiment, the memory 22 stores different operational modes selectable by the operator. For example, the stored operational modes may include instructions for executing a set of modulation parameters associated with a particular treatment site, such as a region of interest in the liver, pancreas, gastrointestinal tract, or spleen. Different sites may have different associated modulation parameters. Rather than the operator manually entering the mode, the controller 16 may be configured to execute the appropriate instructions based on the selection. In another embodiment, the memory 22 stores operational modes for different types of treatment. For example, activation may be associated with different stimulation pressures or frequency ranges versus those associated with inhibiting or blocking tissue function. In a specific example, if the energy application device is an ultrasound transducer, the time-averaged power (time-averaged intensity) and peak positive pressure may be greater than 1 mW / cm. 2 ~30,000mW / cm 2 (time-averaged intensity) and range from 0.1 MPa to 7 MPa (peak pressure). In one example, the time-averaged intensity is 35 W / cm in the region of interest to avoid levels associated with thermal damage and ablation / cavitation. 2 The frequency selected may depend on the mode of energy application.

[0031] In another embodiment, memory 22 stores a calibration or setting mode that allows adjustment or modification of the modulation parameters to achieve a desired result. In one example, stimulation begins with a low energy parameter and gradually increases, either automatically or upon receipt of operator input. In this way, the operator can achieve adjustment of the induced effect while the modulation parameters are changed.

[0032] The system may also include an imaging device to facilitate focusing of the energy application device 12. In one embodiment, the imaging device may be integrated with or the same device as the energy application device 12 so that different ultrasound parameters (frequency, numerical aperture, or energy) can be applied to select (e.g., spatially select) a region of interest and focus energy on the selected region of interest for targeting and subsequent neuromodulation. In another embodiment, the memory 22 stores one or more targeting or focusing modes used to spatially select a region of interest within an organ or tissue structure. The spatial selection may include selecting a subregion of the organ to identify a volume of the organ corresponding to the region of interest. The spatial selection may depend on image data as provided herein. Based on the spatial selection, the energy application device 12 may focus on the selected volume corresponding to the region of interest. For example, the energy application device 12 may be configured to initially operate in a targeting mode to apply targeting mode energy used to capture image data used to identify the region of interest. The targeted mode energy is applied at a level and / or modulation parameters that are not appropriate for preferential activation in the region of interest, however, once the region of interest has been identified and targeted, the controller 16 can then operate in a therapeutic mode according to modulation parameters associated with preferential activation.

[0033] The controller 16 may also be configured to receive input related to a desired physiological outcome as input to the selection of modulation parameters. For example, if an imaging modality is used to assess tissue characteristics, the controller 16 may be configured to receive a calculated index or parameter of the characteristic. The modulation parameters may be altered based on whether the index or parameter is above or below a predefined threshold. In one embodiment, the parameter may be a measure of tissue displacement of the affected tissue or a measure of the depth of the affected tissue. Other parameters may include assessing the concentration of one or more molecules of interest (e.g., assessing one or more of a change in concentration relative to a threshold or baseline / control, a rate of change, or a determination of whether the concentration is within a desired range). Additionally, the energy application device 12 (e.g., an ultrasound transducer) may operate under the control of the controller 16 as follows: (a) acquire tissue image data that can be used to spatially select a region of interest within the target tissue, (b) apply modulated energy to the region of interest, and (c) acquire images to determine that a target physiological outcome associated with a change in a property of interest has occurred (e.g., that a change in a glucose transporter pathway molecule and / or an incretin pathway molecule has occurred (e.g., via displacement measurement)). In such an embodiment, the imaging device, evaluation device 18, and energy application device 12 may be the same device.

[0034] In another embodiment, a desired modulation parameter set may also be stored by the controller 16. In this manner, subject-specific parameters may be determined. Furthermore, the effectiveness of such parameters may be evaluated over time. If the effectiveness of a particular parameter set decreases over time, the subject may be developing insensitivity to the activated pathway. If the system 10 includes an evaluation device 18, the evaluation device 18 may provide feedback to the controller 16. In certain embodiments, the feedback may be received from a user or the evaluation device 18 indicating characteristics of a target physiological outcome. The controller 16 may be configured to cause the energy application device to apply energy according to the modulation parameters and dynamically adjust the modulation parameters based on the feedback. For example, based on the feedback, the processor 20 may automatically change the modulation parameters (e.g., frequency, amplitude, or pulse width of the ultrasound beam or mechanical vibration) in real time in response to feedback from the evaluation device 18.

[0035] With the above in mind, FIG. 3 is a schematic diagram 30 of a transducer arrangement with standoffs as discussed herein, suitable for use in clear path determination in the field of therapeutic neuromodulation, in accordance with an embodiment of the present disclosure. It should be noted that the transducer arrangement is provided by way of example only, and that some components may be omitted and / or additional components may be included. For example, an ultrasound probe in this field may include a therapeutic transducer 32 and an imaging transducer 34. In the depicted example, a concentric transducer configuration is shown in which the array of imaging transducers 34 is centrally located, although a parallel configuration would also be suitable. In this manner, the imaging beam 36 generated by the imaging transducer 34 substantially or completely encompasses the entire acoustic window of the treatment beam 38 generated by the treatment transducer 32. Therefore, determining a clear path for the ultrasound beam may include determining that the patient's target area for treatment is "visible" (i.e., resides within an imaging beam 36) and accessible by the treatment beam 38.

[0036] In certain embodiments, the therapy transducer 32 and the imaging transducer 32 are separated from the patient by a gel standoff 40, as described herein. The disclosed gel standoff 40 can be customized (e.g., sized or dimensioned) in at least one dimension to ensure coverage of the therapy beam 38 path by the imaging beam 36 path above the patient interface, as described herein. Furthermore, unlike conventional standoffs that utilize fluid-filled standoffs with ultrasound coupling gel, the application surface 42 of the gel standoff 40 can be applied directly to the patient's skin. For example, use of the coupling gel may involve multiple applications during a patient imaging / treatment session. Furthermore, excess and dried coupling gel may need to be cleaned from the patient's skin after the session. In this manner, the gel standoff 40 improves the patient experience.

[0037] Regarding the implementation and use of the gel standoffs 40, FIG. 4A is a schematic diagram 50 of the patient-facing portion of an ultrasound probe equipped with the gel standoffs 40. Two different views are shown, corresponding to an azimuth view (left) and an elevation view rotated 90 degrees relative to the azimuth view (right). The disclosed gel standoffs 40 exhibit many advantages, such as providing desirable acoustic characteristics, good image quality, and little clutter, thereby improving patient experience and clinical outcomes. In the depicted example of FIG. 4A, the probe includes an imaging transducer 52 and a therapy transducer 54. In some embodiments, the transducers may be co-centric or adjacently attached. The ultrasound probe may include one or more mating features 56 that allow the gel standoffs 40 to fit into a cavity in the ultrasound probe and be held in place by the mating features 56. In this manner, the gel standoff 40 separates the transducer from the application surface 42. The right-most illustration shows an example of one or more mating features 56, where a partial annular ridge may be used to enable a snap-fit ​​of the gel standoff 40 within the cavity. It should be noted that one or more mating features 56 may be utilized, alone or in combination with one another, to form a fit, including but not limited to, a snap fit, mating ridges (e.g., interference snap fit), cantilever snap fit, annular snap fit, or a torsional fit (i.e., screw-in).The example mating features 56 described herein complement the material properties of the gel standoffs 40 by leveraging the flexibility (e.g., low modulus) of the gel standoffs 40 such that the material elastically deforms and rebounds during insertion, creating an interference force that allows the ultrasound probe and gel standoffs 40 to contact and be held together. In this manner, the mating features 56 allow for a tight fit of the gel standoffs 40 within the cavity of the probe, enabling acoustic coupling at the transducer face for transmission and / or reception of ultrasound energy of the imaging beam 36 and / or therapy beam 38 (e.g., beams 36, 38).

[0038] In general, gel standoffs 40 offer many advantages, including replacing the need for internal coupling oil / liquid, eliminating the need for ultrasound gel, and being able to be designed to accommodate multiple configurations of the ultrasound probe to optimally fit different patients and / or target locations on the patient's body. Furthermore, gel standoffs 40 can be disposable. As such, gel standoffs 40 create a more hygienic process. Importantly, the adaptable (or otherwise non-rigid) configuration of the gel standoffs 40 also allows for more precise positioning (e.g., angle, XY position) of the ultrasound probe on the patient's body, allowing the probe to conform to the target location. Thus, gel standoffs 40 offer a variety of customization opportunities that enable good acoustic coupling.

[0039] For comparison, FIG. 4B is a schematic diagram 70 of the patient-facing portion of an ultrasound probe with a standard cap arrangement. Two different views are shown, corresponding to an azimuth view (left view) and an elevation view rotated 90° relative to the azimuth view (right view). The ultrasound probe is depicted as having an imaging transducer 72, a therapy transducer 74, a standoff 76 (e.g., a fluid-filled standoff as shown, or a solid standoff (not shown)), and a standard cap 78 (e.g., hard plastic). Typically, an internal standoff 48 separates the transducers from the standard cap 78. In some embodiments, the transducers may be concentrically or otherwise adjacently mounted with co-molded lenses or fluid-filled caps over both transducers. Due to the design and type of standoff 76 (e.g., fluid-filled standoff), this embodiment of the probe requires the use of ultrasound coupling gel. Thus, fluid-filled standoffs exhibit many problems compared to gel standoffs 40, such as acoustic reverberations that result in poor image quality, as depicted in FIG. 4A.

[0040] With the foregoing in mind, FIG. 5 is a schematic diagram 100 of a mold 102 that may be used to fabricate gel standoffs 40 according to embodiments of the present disclosure. The mold 102 may exhibit or otherwise include structural features (e.g., ridges, grooves, edges, X / Y / Z dimensions) that enable the mold 102 to form and / or impart geometric features to the gel standoffs 40 during the molding process. In certain embodiments, one or more such features may facilitate engagement of the gel standoffs 40 with an ultrasound probe. Thus, the gel standoffs 40 may be fabricated by providing one or more materials (e.g., hydrogel, solid oil) into the mold 102 in a first flowable or malleable state, and allowing the material to solidify or otherwise harden within the mold to a second state in which it is no longer flowable. In practice, the mold 102 may include an upper template 104 and a lower template 106 that individually and / or together form one or more geometric features in the molded gel standoff 40. By way of example, in one embodiment, the upper template 104 may include features (e.g., ridges, edges, or grooves) that form a transducer mating profile 108 during the molding process. The transducer mating profile 108 allows one or more transducers of an ultrasound probe to reversibly mate or couple to the gel standoff 40. Thus, the transducer mating profile 108 allows for intimate contact between the transducer-side surface of the gel standoff 40 and the transducer, allowing for good acoustic coupling when attached to the probe due to its ability to minimize air pockets between the gel standoff 40 and the transducer.

[0041] Similarly, in certain embodiments, the lower template 106 is used during the molding process to create the application surface, i.e., the surface that faces the patient (e.g., the bottom surface of the gel standoff 40). In such embodiments, the lower template 106 may also include features similar to those of the upper template 104 (e.g., ridges, lips, or grooves) to form retention grooves 110 (or other snap and interference fit structural feature(s)) that can mate with one or more mating features 56 on the ultrasound probe. The retention grooves 110 allow the gel standoff 40 to lock or mate with complementary one or more mating features 56 on the ultrasound probe (e.g., the one or more mating features 56 on the probe function as male alignment features and the retention grooves 110 function as female alignment features) to hold the molded gel standoff 40 in place. This geometric feature allows the gel standoff 40 to be pressed and / or snapped on and remain fixed in place throughout the treatment session. In this manner, the retention grooves 110 allow the gel standoffs 40 to reversibly mate or couple with one or more mating features 56 of an ultrasound probe. The lower template 106 can also create an application surface 42 (e.g., a patient-facing surface). The application surface 42 of the gel standoffs 40 allows the standoffs to be applied directly to a patient's body and / or skin without the need for ultrasound coupling gel. In some embodiments, the upper template 104 can include features for creating the retention grooves 110. Accordingly, it should be noted that the mold 102 (e.g., the upper template 104 and lower template 106) can be configured or customized to include additional features for creating gel standoffs 40 that correspond to alternative ultrasound probe and / or transducer configurations.

[0042] In general, the embodiments described herein allow the gel standoffs 40 to be customized to accommodate various patient body types as well as various neuromodulation applications or needs. For example, in certain embodiments, the gel standoffs 40 can be molded from a single material or composition, such as a hydrogel or a phase-change material (e.g., solid oil, phase-change material). In some embodiments, the gel standoffs 40 may be molded from multiple materials or compositions to create multi-layered structures, or more generally, to create gel standoffs 40 with distinguishable structures or features (i.e., non-uniform) formed therein, such as by using different compositions for different internal features. In other embodiments, the gel standoffs 40 may be molded from a combination of multiple materials, which can improve acoustic performance by eliminating or reducing abrupt transitions or boundaries due to multi-layered structures (e.g., by forming gradients or transitions (i.e., gradient-based materials)), thereby reducing or eliminating reflections due to such boundaries. In this manner, the material and / or structural properties of the gel standoffs 40 can be selected to spatially configure specific desired acoustic properties, such as attenuation and impedance.

[0043] The composition of the gel standoff 40 can include, but is not limited to, biocompatible, cross-linked hydrogels such as polyacrylamide, acrylate-siloxane, alkoxysilane, hyaluronic acid and derivatives, and copolymers and derivatives thereof. Additionally, the hydrogels can be filled or otherwise contain additives other than water (e.g., water soluble additives—glycerin, polyethylene glycol, or hydrophobic additives) that can help maintain lubricity on the skin while maintaining an intimate bond. Alternatively, synthetic, non-hydrogel elastomeric materials can be utilized, including, but not limited to, highly plasticized polyurethanes (e.g., plasticized elastomeric polymers) and divinyl olefin polymers. Any of these materials may be formulated with additives to enhance lubrication, prevent dryness, and prevent skin irritation. Exemplary materials include silicones (dimethicone, cyclomethicone (e.g., cyclopentasiloxane)), fatty acid esters (e.g., palmitates), and other moisturizing ingredients commonly used in skincare.

[0044] Additionally, the gel standoffs 40 can be customized to exhibit a thickness (e.g., in the Z direction) ranging from about 0.5 to about 6 centimeters (cm), e.g., about 0.5 to about 5 cm, about 0.5 to about 4 cm, about 0.5 to about 3 cm, about 0.5 to about 2 cm, or about 1 to 2 cm. The gel standoffs can be approximately 200 cm in the X and Y dimensions. 2 The following areas can be shown: For example, for a concentric transducer arrangement with an outer circular treatment transducer of 6 cm diameter, the gel standoffs should be approximately 6 cm in diameter (approximately 28.3 cm in area) in the XY direction to allow good acoustic coupling across the entire surface of the transducer and sufficient contact with the patient's skin. 2 ) In general, the dimensions of the gel standoffs 40 and / or the shape of the gel standoffs 40 can be customized based on the transducer shape, the patient's body type, and / or the target location. For example, the gel standoffs 40 can be customized to be thinner overall or in specific areas to properly fit and deliver ultrasound energy accordingly to patients with a high body mass index (BMI) (e.g., obese patients). Alternatively, patients with a lower BMI may require a thicker gel standoff 40 overall or in specific areas to better direct the ultrasound energy to the region of interest. As such, the gel standoffs 40 offer various advantages to accommodate a variety of neuromodulation applications for treating various clinical conditions.

[0045] As an example, FIG. 6 shows a schematic diagram of the patient-facing portion of an ultrasound probe equipped with the gel standoff 40 of FIG. 4A in accordance with an embodiment of the present disclosure. As discussed with respect to FIG. 4A, the gel standoff 40 can be custom molded to fit the shape of the transducer so that there is good coupling of acoustic energy from the transducer to the gel standoff 40 after insertion. In this manner, and as shown in this example, there is no air gap, as represented by line 112, between the transducer and the transducer side of the gel standoff 40. Based on the composition of the gel standoff 40, the gel standoff 40 may be pre-wetted to ensure good coupling. For example, the gel standoff 40 can be dipped or sprayed with water on the transducer side before insertion into the ultrasound probe. In some embodiments, the gel standoff 40 may be "wet" packaged for insertion from the package. In other embodiments, the material composition of the gel standoff 40 may be naturally "wet" (e.g., a self-wetting material) or may undergo a phase change to become "wet" during use. In this manner, the gel standoff 40 can enable good coupling of acoustic energy from the transducer. In some embodiments, the gel standoffs 40 may be composed of a uniformly or evenly distributed material (e.g., a single material composition such that the gel standoffs are composed only of a hydrogel or solid oil).

[0046] With the above in mind, FIG. 7 shows a schematic diagram of the patient-facing portion of an ultrasound probe with the gel standoff 40 of FIG. 4A having a complex structure. The gel standoff 40 can be customized to provide desired acoustic characteristics based on the characteristics of the standoff and / or can have a more complex structure, such as being fabricated using multiple materials to create a multi-layered standoff or a multiple-material standoff. For example, an ultrasound probe with a gel standoff 40 having internal structures or features and / or multiple layers ( FIG. 7 ) may be used, and the gel standoff 40 may be configured to include a lens 116. The lens 116 may be incorporated into the gel standoff 40 to provide desired focusing in azimuth, elevation, and / or depth, as shown by the angled beam path 118, and may be made from a rigid or non-rigid material. Thus, the lens 116 (e.g., lens material) can be designed to exhibit various shapes to accommodate different patient body shapes, target anatomical regions at various depths, and / or aid in angling the beam (e.g., imaging beam, treatment beam) toward the target or region of interest. In this manner, the gel standoffs 40 provide customizable focusing for neuromodulation applications.

[0047] With the foregoing in mind, FIG. 8 is a schematic diagram 120 of a gel standoff 40 housed in a container 122 provided as part of a disposable gel pad pack 124 in accordance with an embodiment of the present disclosure. The gel standoff 40 may be packaged in the container 122 along with a fluid as part of the gel pad pack 124, thereby providing the gel standoff 40 to the user as a disposable, single-use product. The container 122 may also include a lid 128 (e.g., a plastic cover) to properly contain the gel standoff 40 and a fluid solution or water bath 126 (e.g., packing or wetting fluid) during shipping and storage. For example, the container 122 may contain a gel standoff 40 stored in the fluid solution or water bath 126. In particular, a gel standoff 40 made of a hydrogel may be stored in the fluid solution or water bath 126. In some embodiments, a gel standoff 40 made of a solid oil may not require a fluid solution or water bath 126. In this manner, the container 122 may be designed to facilitate or otherwise accommodate good acoustic coupling between the ultrasound probe transducer and the gel standoffs 40. For example, the container 122 may be sized so that a user can bring the container 122 toward the ultrasound probe transducer (e.g., probe head) and insert / lock the gel standoffs 40 into place. Thus, the gel standoffs 40 may be packaged in a kit and utilized for an individual patient.

[0048] 9, an exemplary workflow of a method 130 for attaching gel standoffs 40 to an ultrasound probe is provided, according to an embodiment of the present disclosure. Method 130 includes various steps, which are represented by images. While the exemplary workflow illustrates the steps in a fixed order, it should be understood that the steps may be performed in any suitable order, and that certain steps may be performed simultaneously, where appropriate. Additionally, steps may be added or omitted from method 130.

[0049] The method 130 may begin at step 132, where a user may obtain a disposable gel pad pack 124 (e.g., gel standoffs 40 in a container 122) in preparation for the application of ultrasound energy to induce neuromodulation in a patient. As previously described in FIG. 7 , the gel pad pack 124 may include gel standoffs 40 in a container 122, which may be stored in a fluid solution or water bath 126 and secured within the container 122 by a lid 128. As such, the user may begin by first removing the lid 128 (or peeling off a thin plastic cover) from the container 122. In some embodiments, the user may briefly rinse the gel standoffs 40 in the container 122 with water or other suitable fluid to wet the gel standoffs 40.

[0050] In step 134, a user may prepare the gel standoffs for insertion into complementary volumes formed as part of the ultrasonic probe 131, such as formed in a portion of the probe head of the ultrasonic probe. This may be accomplished by bringing the pad pack 124 toward the ultrasonic probe 131. Then, in step 136, the user may align the central axis of the ultrasonic probe 131 over the gel pad pack 124 containing the gel standoffs 40. As depicted in FIG. 5 , the gel standoffs 40 and the ultrasonic probe 131 may include complementary features (e.g., male / female or slot and groove alignment features) to enable the gel standoffs 40 to securely engage with the ultrasonic probe 131. For example, the gel standoffs 40 and the ultrasonic probe 131 may include geometric features such as grooves and ridges (e.g., the transducer mating profile 108 and the retention groove 110) to enable the gel standoffs 40 to securely engage with the cavities of the ultrasonic probe 131. Similarly, the ultrasonic probe 131 may include grooves and ridges to allow for proper fitment of the gel standoffs 40 within the cavity of the probe. Additionally, the inner walls of the pad pack 124 may be sized to match the outer dimensions of the ultrasonic probe 131 to be inserted so that alignment of the ultrasonic probe 131 with the pad pack 124 and / or gel standoffs 40 may be easily achieved.

[0051] In step 138, the user can apply pressure to the gel pad pack 124 by pressing the gel standoffs 40 in the gel pad pack 124 toward the ultrasound probe 131 to engage the gel standoffs 40 with the ultrasound probe 131. This action causes the gel standoffs 40 to release contact with the gel pad pack 124 and "snap" or "suck" into place. In some embodiments, the ultrasound probe 131 can be pressed toward the gel pad pack 124. For example, the gel pad pack 124 can be placed on a surface, and the ultrasound probe 131 can then be pressed into the pad pack 124. Then, in step 140, the user can lift the ultrasound probe 131, including the gel standoffs 40, to release contact and separate it from the container 122. The user can discard the remaining packaging of the gel pad pack 124.

[0052] In step 142, the user applies or engages the ultrasound probe 131 (and attached gel standoffs 40) to the patient, after which ultrasound may be administered to induce neuromodulation in the patient until the neuromodulation protocol is complete. Thereafter, in step 144, the ultrasound probe 131 may be moved away from the patient, and the gel standoffs 40 may be detached from the ultrasound probe 131. For example, the ultrasound probe 131 may include an eject button for detaching the gel standoffs 40 from the ultrasound probe 131. In this manner, the gel standoffs 40 may be appropriately discarded in a trash can 146. It should be noted that the ultrasound probe 131 may capture residue from the gel standoffs 40. As such, the user may rinse the ultrasound probe 131 with water (or perform other disinfection procedures) as needed until any remaining gel residue is removed. Accordingly, the gel pad packs 124 described herein utilize a water-based procedure that enables a no-touch workflow, thereby providing an overall positive user experience.

[0053] 10A, 10B, and 10C are schematic diagrams 150 corresponding to different procedures for removing the gel standoff 40 from the ultrasound probe 131 according to different embodiments of the present disclosure. In certain implementations, the gel standoff 40 is a disposable, single-use product. Thus, the gel standoff 40 can be removed after applying energy to the patient as part of a neuromodulation protocol. In one embodiment, the shape of the gel standoff 40 can be designed to protrude sufficiently from the outer lip of the ultrasound probe 131 so that the gel standoff 40 can be grasped and peeled away. In another embodiment, shown in FIG. 10A, a pull tab method 152 can be utilized to remove the gel standoff 40. The gel standoff 40 can be designed with a pull tab 154 structure attached to or integrally formed with the gel standoff 40 that can protrude from the side of the ultrasound probe 131 while the gel standoff 40 is secured thereto. A user can remove the gel standoff 40 from the ultrasound probe 131 by grasping the pull tab 154, peeling it away from the ultrasound probe 131, and discarding it in a trash can 146. The outer circumferential retention groove 110 of the gel standoff 40 may thus physically disengage (e.g., uncouple) from the complementary mating ridge 64 of the ultrasound probe, and the transducer mating profile 108 may disengage from one or more transducers to release the gel standoff 40. The pull tab 154 may be integrated into the gel standoff 40 during its molding process, thereby exhibiting a similar chemical composition to the gel standoff (e.g., a hydrogel or solid oil). Alternatively, in some embodiments, the pull tab 154 may be designed from another material that exhibits strong mechanical properties to withstand pulling forces. Thus, the presence of such geometric features makes the insertion and removal of the gel standoff 40 a reversible mating process.

[0054] In another embodiment shown in FIG. 10B , an edge hinge method 156 can be used to remove gel standoffs 40 that are in contact with one or more transducers 162 within an ultrasound probe 131. For example, the ultrasound probe 131 can include a button or other mechanical actuation mechanism that controls movement of one or more edges 158 of the ultrasound probe 131 via a hinge 160. For example, the hinge 160 can be a hinge having two separate parts that rotate relative to one another. In some embodiments, the hinge 160 can be a flexure hinge configured on the cap of the ultrasound probe 131. Thus, an ultrasound transducer probe 131 with a flexure hinge can provide the necessary engagement of a lip-and-groove or other movable snap-fit ​​feature. The edge 158 of the ultrasound probe 131 can be designed to include a mating ridge 64 that engages with a retaining groove on the gel standoff 40 to secure the gel standoff within the ultrasound probe 131 when the edge 158 is in the engaged configuration ( FIG. 10B , left). To remove the gel standoff 40 from the ultrasound probe 131, a user can press a button (or other mechanical actuation mechanism) on the ultrasound probe 131 to release the edge 158 at the hinge 160 (placing the engagement mechanism in a disengaged configuration) and disengage the mating ridge 64 from the gel standoff 40 ( FIG. 10B , right). In this way, the gel standoff 40 can be released and dropped, after which the user can discard the standoff in a trash can 146.

[0055] In some embodiments shown in FIG. 10C , an air pump method 164 can be used to secure and remove the gel standoff 40 from the ultrasonic probe 131. For example, the ultrasonic probe 131 may be designed to include a valve 166 that controls the direction of air flow within the tubing and engagement volume of the ultrasonic probe 131. For example, the insertion step 168 ( FIG. 10C , left) can include air being directed outward to create a partial vacuum within the cavity between the probe inner surface and the gel standoff 40. In response to the partial vacuum, the gel standoff 40 is held firmly within the cavity, and residual air is thereby removed, thereby improving the coupling between the transducer face and the gel standoff 40. To remove the gel standoff 40, the removal step 170 ( FIG. 10C , right) can include flowing air against the gel standoff 40 and into the cavity to create a relative overpressure within the cavity. The relative overpressure within the cavity effectively pushes the gel standoff 40 out of the cavity of the ultrasound probe 131, thereby allowing the user to discard the gel standoff 40 in a trash can 146. It should be noted that additional components may be integrated as part of the air pumping method to control the air pressure and / or direction of air flow to insert and remove the gel standoff 40 from the ultrasound probe 131. Furthermore, the gel standoff 40 may exhibit different shapes that may be compatible with the air pumping method. For example, the gel standoff 40 may not include some of the geometric features (e.g., the transducer mating profile 108 and the retention groove 110).

[0056] With the above in mind, FIG. 11 is a schematic diagram 180 of the use of an alternative composition of a gel standoff 40 in accordance with an embodiment of the present disclosure. As described in FIG. 5, the composition of the gel standoff 40 may, in certain embodiments, be designed to include a single material, where the entire gel standoff 40 is made of a hydrogel or phase change material. In other embodiments, the gel standoff 40 may be designed as a multi-layer material. Accordingly, FIG. 11 illustrates how the gel standoff 40 may be designed as a multi-layer material. For example, the gel standoff 40 may be designed such that the application surface 42 (i.e., the surface or patient-facing layer) is composed of different materials, where the transducer-side surface of the gel standoff 40 may be a hydrogel and the patient-side (i.e., application surface 42) of the gel standoff may be a phase change material 182 (e.g., a solid oil, a wax). A phase change material 182, as used herein, is a material that begins to undergo a phase change from solid to liquid when its melting temperature approximately matches the temperature of the material it is in contact with. Thus, a material can be selected that changes phase to a "wet" state upon contact with a patient's skin, which is assumed to be at a temperature above room temperature. For example, the phase change material may be a solid oil that is solid at room temperature (e.g., about 25°C) and exhibits a melting temperature (i.e., begins to melt) in the range of about 30°C to about 40°C (e.g., average human body temperature). For example, the phase change material may melt at a temperature in the range of about 33°C to about 37°C. In this manner, the phase change material 182 may be self-wetting, or naturally wettable, and be able to lubricate itself during the energy application process.

[0057] Furthermore, in other embodiments, the gel standoff 40, including a multi-layered material or a gradient-based material, can be designed to exhibit properties such as elastic modulus, lubricity, and varying acoustic modulus. For example, the elastic modulus of the gel standoff 40 can be varied as a multi-layered material, such that the application side exhibits a soft elastic modulus (e.g., a soft material) for skin contact, while the ultrasound probe side exhibits a harder elastic modulus (e.g., a hard material). The lubricity of the gel standoff 40 can be customized so that the application side exhibits a slippery surface for skin contrast. In contrast, the probe side of the gel standoff 40 can exhibit a more tacky surface to enable good contact and conformance of the gel standoff 40 to the cavity of the ultrasound probe. Furthermore, the gel standoff 40 can be customized with varying acoustic modulus to avoid reflections. For example, the gel standoffs 40 may be molded from a combination of materials to form a gradient-based material, which can improve acoustic performance by eliminating or reducing abrupt transitions or boundaries that may be associated with multi-layered gel standoffs 40, thereby reducing or eliminating reflections caused by such boundaries.

[0058] In another embodiment, the phase change material 182 may change phase in response to ultrasound energy passing through it as part of a treatment procedure, rather than based on a change in temperature. In other embodiments, the gel standoff 40 may be designed with only a single material (e.g., a hydrogel or solid oil) that initiates a phase change at the patient-contacting surface upon contact with the patient's skin. As such, the phase change material 182 may exhibit a gradient response to temperature. For example, the phase change material 182 may exhibit a higher melting temperature near the transducer (e.g., near the transducer side) and a lower melting temperature near the patient-contacting surface (e.g., the application surface 42). In some embodiments, the cap 184 may be designed with a composition consisting of the phase change material 182. Thus, a user can secure or attach the cap 184 to the gel standoff 40 prior to applying ultrasound energy to the patient's skin. It should be noted that the composition of the gel standoff may be selected so that it does not completely change phase during the energy application process. Additionally, it should be noted that the use of the phase change material 182 does not require the use of an ultrasound gel during the energy application process. In this manner, ultrasound energy application (e.g., as part of a neuromodulation protocol) can be performed in the absence of traditional ultrasound gel. In this manner, the gel standoffs 40 can be customized to provide good acoustic coupling and energy application to the patient.

[0059] FIG. 12 compares ultrasound image quality acquired with a standard cap arrangement 42 (e.g., a fluid-filled cap) versus a gel standoff. Generally, ultrasound images 200 and 202 are images of a wire target within an ultrasound phantom. Ultrasound image 200 was acquired with a fluid-filled cap arrangement utilizing a glycerol-filled polymethylpentene cap, and ultrasound image 202 was acquired with a gel standoff 40. Thus, the gel standoff 40 allows for high-quality imaging with clear resolution of the wire target, as shown in ultrasound image 202. In contrast, ultrasound image 200 acquired with the fluid-filled cap has much higher reverberation content, compromising image contrast and resolution. Thus, the gel standoff 40 reduces reverberation and allows for a significant improvement in image quality compared to a fluid-filled cap.

[0060] 13 is a schematic diagram 220 of a gel standoff 40a with an increased thickness. Generally, the schematic diagram 220 includes a gel standoff 40a that is shaped to exhibit an increased thickness compared to other embodiments described herein. Thus, when the gel standoff 40a is applied to a patient's surface 222, the increased thickness enables delivery of ultrasound energy (e.g., a treatment beam and / or an imaging beam) that targets shallow anatomical features 222.

[0061] With the above in mind, FIG. 14 is a schematic diagram 230 of an angled (e.g., pre-angled) gel standoff 40b. Generally, the schematic diagram 230 includes a gel standoff 40b, where the angled gel standoff 40b is shaped to exhibit an angle-like feature. In this manner, the angled gel standoff 40b is applied to a patient's skin 222, allowing the treatment beam to be directed toward a target anatomy 232 for a particular ultrasound therapy application. The angle can be one or more degrees of freedom (DOF) to aid in pre-orienting the ultrasound probe. Furthermore, if the ultrasound probe needs to be substantially angled relative to the patient's skin 222, one side of the probe will naturally tend to lift. As such, customizing the gel standoff 40b to be thicker on one side relative to the other can help maintain the gel standoff 40b's coupling.

[0062] As a further example, FIG. 15 is a schematic diagram 240 of a custom-shaped gel standoff 40c for a patient. Generally, the schematic diagram 240 includes a custom-shaped gel standoff 40, which is designed to fit the patient's profile. For example, the gel standoff 40c may be customized when a determined probe placement location for the patient has a greater-than-average degree of surface contouring of the patient's skin 222 that may make it difficult to maintain contact with the skin surface 222. In this manner, the gel standoff 40c can conform to the patient's skin 222 at the ultrasound probe placement location, thereby enabling delivery of an ultrasound treatment beam toward the target anatomical structure 242.

[0063] Further aspects of the invention are provided by the subject matter of the following clauses. [Embodiment 1] A gel standoff, a gel standoff body comprising a moldable material; one or more mating features formed within the gel standoff body, wherein the one or more mating features are configured to conform to one or more structural features of an ultrasound probe; and a skin-facing surface, wherein the skin-facing surface is configured to contact a subject's skin when in use. [Embodiment 2]

[0023] The gel standoff of any preceding embodiment, wherein the moldable material comprises a hydrogel. [Embodiment 3]

[0023] The gel standoff of any preceding embodiment, wherein the moldable material comprises a phase changing material. [Embodiment 4] 10. The gel standoff of any preceding embodiment, wherein the phase changing material changes phase at least partly in response to a temperature of the phase changing material reaching or exceeding a melting point threshold. [Embodiment 5] 10. The gel standoff of any preceding embodiment, wherein the phase changing material exhibits a melting temperature ranging from about 30°C to about 40°C. [Embodiment 6]

[0023] The gel standoff of any preceding embodiment, wherein the moldable material comprises a plasticized elastomeric polymer. [Embodiment 7]

[0023] The gel standoff of any preceding embodiment, comprising a multi-layered material. [Embodiment 8]

[0013] The gel standoff of any preceding embodiment, wherein the moldable material is customized based on depth of a region of interest, to conform to a patient profile, to pre-angulate an ultrasound probe in a certain direction, or a combination thereof. [Embodiment 9]

[0023] The gel standoff of any preceding embodiment, wherein the one or more mating features comprise one or more of a snap fit, interference fit, cantilever fit, annular fit, or torsional fit alone or in combination with one another. [Embodiment 10] 10. The gel standoff of any preceding embodiment, wherein the one or more mating features are configured to reversibly mate with one or more complementary structural features of the ultrasound probe. [Embodiment 11] 10. The gel standoff of any preceding embodiment, wherein the phase changing material changes phase at least partly in response to acoustic energy. [Embodiment 12] 10. The gel standoff of any preceding embodiment, wherein the gel standoff body comprises a self-wetting material. [Embodiment 13] 10. The gel standoff of any preceding embodiment, wherein the gel standoff is packaged into a container comprising a wetting fluid. [Embodiment 14] A method of mounting a gel standoff to an ultrasound probe, comprising: opening a gel pad pack, wherein the gel standoff is exposed in the gel pad pack when opened; aligning the gel pad pack with an ultrasound probe, wherein one or more mating features of the gel standoff are aligned with complementary mating features of the ultrasound probe when aligned; contacting the gel standoff in the gel pad pack with the ultrasound probe, wherein the gel standoff engages with the ultrasound probe in response to the contact; separating the ultrasound probe from the gel pad pack; A method comprising: [Embodiment 15]

[0023] 3. The method of any preceding embodiment, wherein the one or more mating features of the gel standoff comprise at least a snap and interference fit structural feature. [Embodiment 16] 10. The method of any preceding embodiment, wherein the mating features are integrated into the profile of the ultrasound probe. [Embodiment 17] 10. The method of any preceding embodiment, wherein the mating feature is configured to couple to a complementary mating feature of the gel standoff. [Embodiment 18] 10. The method of any preceding embodiment, wherein the gel standoff is configured to allow acoustic energy generated by the ultrasound probe to pass through. [Embodiment 19] 1. A method of using a gel standoff, comprising: inserting the gel standoff into a complementary cavity of an ultrasound probe; pressing the ultrasound probe against a subject; applying energy through the gel standoff toward a region of interest in the subject to cause neuromodulation; removing the gel standoff from the ultrasound probe after the energy application is complete; A method comprising: [Embodiment 20] 10. The method of any preceding embodiment, wherein the energy is applied in the absence of acoustic gel. [Embodiment 21] 10. The method of any preceding embodiment, wherein the gel standoff is removed by peeling the standoff out of the ultrasound probe. [Embodiment 22] 10. The method of any preceding embodiment, wherein the gel standoff is removed using an application of air pressure and relative overpressure.

[0064] 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 any methods incorporated therein. 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]

[0065] 10: Neuromodulation system 12: Energy application device 14: Pulse generator 16: Controller 18: Evaluation device 20: Processor 22: Memory 24: Input / output (I / O) circuitry 26: Display 28: Lead 32: Treatment transducer 33: Lead wire 34: Imaging transducer 36: Imaging beam 38: Treatment beam 40: Gel standoff 40a: Thickened gel standoff 40b: Angled gel standoff 40c: Custom molded gel standoff 42: Application surface 52: Imaging transducer 54: Treatment transducer 56: Mating feature 72: Imaging transducer 74: Treatment transducer 76: Standoff 78: Standard cap 102: Mold 104: Upper template 106: Lower template 108: Transducer mating profile 110: Retention groove 112: Line 116: Lens 118: Angled beam path 122: Container 124: Disposable gel pad pack 126: Water bath 128: Lid 131: Ultrasound probe 146: Trash can 154: Pull tab 156: Edge-hinge method 158: Edge 160: Hinge 162: Transducer 164: Air pump method 166: Valve 168: Insertion step 170: Removal step 182: Phase change material 184: Cap 200, 202: Ultrasound image 222: Skin 232, 242: Target anatomical structure

Claims

1. A gel standoff, a gel standoff body comprising a moldable material; one or more mating features formed within the gel standoff body, the one or more mating features configured to mate with one or more structural features of an ultrasound probe; a skin-facing surface configured to contact the skin of a subject in use.

2. The gel standoff of claim 1 , wherein the moldable material comprises a hydrogel.

3. The gel standoff of claim 1 , wherein the moldable material comprises a phase change material.

4. 4. The gel standoff of claim 3, wherein the phase change material changes phase at least in part in response to the temperature of the phase change material reaching or exceeding a melting point threshold.

5. The gel standoff of claim 4 , wherein the phase change material exhibits a melting temperature in the range of about 30° C. to about 40° C.

6. The gel standoff of claim 1 , wherein the moldable material comprises a plasticized elastomeric polymer.

7. The gel standoff of claim 1 , comprising a multi-layer material.

8. 10. The gel standoff of claim 1, wherein the moldable material is customized based on a depth of an area of ​​interest, to fit a patient profile, to pre-attach an ultrasound probe in a particular direction, or a combination thereof.

9. The gel standoff of claim 1 , wherein the one or more mating features comprise one or more of a snap fit, an interference fit, a cantilever fit, an annular fit, or a twist fit, alone or in combination with each other.

10. The gel standoff of claim 1 , wherein the one or more mating features are configured to reversibly mate with one or more complementary structural features of the ultrasound probe.

11. The gel standoff of claim 3 , wherein the phase change material changes phase at least partially in response to acoustic energy.

12. The gel standoff of claim 1 , wherein the gel standoff body comprises a self-wetting material.

13. The gel standoff of claim 1 , wherein the gel standoff is packaged in a container containing a wetting fluid.

14. 1. A method of attaching gel standoffs to an ultrasound probe, comprising: opening a gel pad pack, wherein upon opening, the gel standoffs are exposed within the gel pad pack; aligning the gel pad pack with an ultrasound probe, wherein upon alignment, one or more mating features of the gel standoffs align with complementary mating features of the ultrasound probe; contacting the gel standoffs in the gel pad pack with the ultrasound probe, the gel standoffs engaging the ultrasound probe in response to the contact; Separating the ultrasound probe from the gel pad pack; A method comprising:

15. The method of claim 14 , wherein the one or more mating features of the gel standoff include at least snap-fit ​​and interference-fit structural features.

16. The method of claim 14 , wherein the mating features are integrated into the contour of the ultrasonic probe.

17. The method of claim 14 , wherein the mating feature is configured to mate with a complementary mating feature of the gel standoff.

18. The method of claim 14 , wherein the gel standoffs are configured to pass acoustic energy generated by the ultrasound probe.

19. 1. A method of using a gel standoff, comprising: inserting the gel standoff into a complementary cavity in an ultrasound probe; pressing the ultrasonic probe against a subject; applying energy through the gel standoff toward the region of interest of the subject to induce neuromodulation; removing the gel standoff from the ultrasound probe after the energy application is complete; A method comprising:

20. 20. The method of claim 19, wherein the energy is applied in the absence of an acoustic gel.

21. 20. The method of claim 19, wherein the gel standoffs are removed by peeling the standoffs from the ultrasound probe.

22. 20. The method of claim 19, wherein the gel standoffs are removed using the application of air pressure and a relative overpressure.

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