WO2026006738A1 - Systems and methods for applying ultrasound to a target region - Google Patents

Abstract

Ultrasound systems for at-home use and methods of using the ultrasound systems to treat various conditions on a subject are discussed herein. The ultrasound system includes a controller and one or more transducers operably coupled to the controller. The one or more transducers are configured to selectively generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate a target region of the body of the subject without ablating the target region. The ultrasonic waves generated by the one or more transducers have a focal width that is at least about three millimeters and larger than the target region of the body of the subject. This inclusive approach obviates the need for precision guidance. It is particularly useful for low-intensity ultrasound applications that are considered safe.

Description

SYSTEMS AND METHODS FOR APPLYING ULTRASOUND TO A TARGET REGION

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Patent Application No. 63/666,156 filed on June 29, 2024 and titled “Systems and Methods for Applying Ultrasonic Neuromodulation Repeatedly at Home” and to United States Provisional Patent Application No. 63/707,145 filed on October 14, 2024 and titled “Systems and Methods for Repeated and Reproducible Ultrasonic Stimulation of Organs and Structures in Outpatient Settings and at Home,” which are hereby incorporated by reference in their entirety.

TECHNICAL FIELD

[0002] The present disclosure relates to systems and methods for applying ultrasound to a specified target region in the human body for repeated and reproducible use in outpatient settings or at home, including techniques which may obviate the need for precision guidance.

BRIEF DESCRIPTION OF THE , SEVERAL VIEWS OF THE DRAWINGS

[0003] The embodiments disclosed herein will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. The drawings depict only typical embodiments, which embodiments will be described with additional specificity and detail in connection with the drawings in which:

[0004] FIG 1 illustrates a perspective view of an ultrasound system with a head of a subject, according to embodiments herein.

[0005] FIG. 2 is a schematic drawing of the ultrasound system of FIG. 1 with the target region in the head of the subject, according to embodiments herein.

[0006] FIG. 3 is a side view of an ultrasound system on a body of a subject, according to embodiments herein.

[0007] FIG. 4 is a front view of the ultrasound system of FIG 3 on the body of the subject, according to an embodiment.

[0008] FIG. 5 is a flow diagram of a method, according to embodiments disclosed herein.

[0009] FIG. 6A is a top view of a wearable ultrasound system with a head of a subject, according to another embodiment

[0010] FIG. 6B is a side view of the wearable ultrasound system of FIG 6A.

[0011] FIG 6C is a front view of the wearable ultrasound system of FIG 6A

[0012] FIG 6D is a top perspective view of the wearable ultrasound system of FIG 6A

DETAILED DESCRIPTION

[0013] Neuromodulation, also referred to as bioelectronic medicine, is emerging as a potentially transformative field that may bypass the use of drugs to control the activity or action of specific organs. To do so, neuromodulation applies electromagnetic or ultrasonic energy to specific body parts, such as neural structures or internal organs. The energy modulates the neural structures or body organs, such that their function is changed in the desired way, while other parts of the body are spared of the intervention, thereby minimizing side effects. Neuromodulation is typically performed using electromagnetic or ultrasonic fields. Ultrasound has the benefit that the energy can be delivered into deep structures or organs in a focused manner and without being substantially diminished with distance from the energy source. This way, it is possible to modulate the activity of neural structures and organs positioned deep in the body, without excessive or potentially harmful effects on the skin or other structures near the source of the energy.

[0014] For neuromodulation, ultrasound is typically used at low intensity, which prevents mechanical or thermal damage. The effects of low-intensity ultrasound (henceforth referred to as “ultrasound”) are fully reversible, which mitigates side effects. Ultrasound has been used to ameliorate the symptoms of multiple disorders, including inflammation, pain, glucose-metabolism- related disorders, disorders of heart function, and various mental and neurological disorders. However, these applications typically use a tightly-focused ultrasound While a tightly-focused ultrasound may appear favorable in regard to minimizing potential side effects, it suffers from two major drawbacks. First, focused ultrasound requires precision guidance that is practically difficult to achieve. Second, applications to human subjects are typically associated with movements of either the subject or the target organ, which further complicates targeting.

[0015] With specific respect to brains, many disorders of brain function involve neural networks situated deep in the brain, including limbic, basal ganglia, and brain stem networks. Progress in treatments of brain disorders has been hampered by the lack of tools to effectively and safely modulate and reset these circuits Deep brain stimulation (DBS) has shown promise in providing a selective reset of the involved deep brain circuits, but the surgical implantation of stimulating leads is associated with high costs and risks, including brain hemorrhage, infection, and in some cases, death.

[0016] On the other hand, conventional noninvasive neuromodulation modalities do not have the necessary spatial resolution at depth. Electroconvulsive therapy (ECT) resets the deep brain structures using large currents that induce brain-wide seizures. This broad activation often results in cognitive side effects such as memory loss. Transcranial magnetic stimulation (TMS) can modulate cortical regions; the fields are weak at the deep brain regions involved in mental disorders TMS can likely modulate deep brain networks via connections with the stimulated cortical regions, but this indirect effect has contributed to variable responses.

[0017] Low-intensity transcranial focused ultrasound combines the depth and precision of DBS with the noninvasiveness of TMS. However, the effects of ultrasonic neuromodulation have been reported to be only transient, lasting at most on the order of 1 hour Therefore, sustained, therapeutic effects require frequently repeated applications, akin to repeated daily applications of TMS Moreover, with specific respect to the brain and compared to TMS, ultrasound poses minimal risk of seizures, which enables in-home applications without the need for reducing the deposited energy.

[0018] Because neuromodulation is reversible, neuromodulation is best applied repeatedly to provide sustained benefits. The use of neuromodulation in outpatient settings or at home, according to this disclosure provides delivery or repeated stimulation necessary for sustained improvements of the disease symptoms. Conventional ultrasonic neuromodulation devices have tight focus that cannot be used in such settings without precision guidance that requires using specifically trained staff for magnetic resonance imaging (MRI), computerized tomography (CT), and/or ultrasounds, thereby dramatically reducing the practicality and use of the stimulation. Furthermore, conventional systems do not stabilize the head or other region of the body for reproducible applications. Operations without precision guidance or without head/body stabilization can lead to the desired target being missed, which would compromise the effectiveness and robustness of the neuromodulation In contrast, the methods and systems disclosed herein enable use of neuromodulation in outpatient settings or at home without MRI or other precision imaging guidance, and under mechanisms for reproducible positioning or stabilization.

[0019] Embodiments of the ultrasound systems disclosed herein may be used or adapted for use with various parts or regions of the body. Accordingly, it will be understood that while specific examples recited herein may refer to use of the ultrasound system to treat symptoms or conditions related to the brain, spleen, liver, pancreas, heart, dorsal root ganglion, or peripheral nerves, analogous concepts, devices, and systems may be used on/with various other anatomical regions of the body.

[0020] The phrases “coupled to” and “in communication with” refer to any form of interaction between two or more entities, including mechanical, electrical, magnetic, electromagnetic, fluid, and thermal interaction Two components may be coupled to or in communication with each other even though they are not in direct contact with each other. For example, two components may be coupled to or in communication with each other through an intermediate component.

[0021] The directional terms “proximal” and “distal” are used herein to refer to opposite locations relative to a medical device in use by a practitioner. The proximal end of the device is defined as the end of the device closest to the practitioner when the device is in use by the practitioner. The distal end is the end opposite the proximal end.

[0022] Embodiments may be understood by reference to the drawings, wherein like parts are designated by like numerals throughout It will be understood by one of ordinary skill in the art having the benefit of this disclosure that the components of the embodiments, as generally described and illustrated in the figures herein, could be arranged and designed in a wide variety of different configurations. Thus, the following, more detailed description of various embodiments, as represented in the figures, is not intended to limit the scope of the disclosure, but is merely representative of various embodiments. While the various aspects of the embodiments are presented in drawings, the drawings are not necessarily drawn to scale unless specifically indicated

[0023] It will be appreciated that various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure. Many of these features may be used alone and/or in combination with one another.

[0024] In many embodiments, an ultrasound system (e.g., ultrasound-based neuromodulation system) for at-home or outpatient use is disclosed. An ultrasound system may comprise a controller and one or more transducers operably coupled to the controller and configured to selectively generate ultrasonic waves at a low frequency (e.g., about 100 kHz to about 400 kHz) effective to stimulate a target region of a body of a subject without ablating the target region. The ultrasonic waves generated by the one or more transducers have a focal width that is at least about three millimeters and/or larger than the target region of the body of the subject In some embodiments, the focal width may be determined solely in relation to the size of the target area, embodiments where there is no absolute minimize size of the focal width are within the scope of this disclosure. For example, embodiments wherein the target region is at least two times larger than the target region, regardless of the absolute size of the focal width are within the scope of this disclosure. Similar focal widths at least three times, at least four times, at least 1.5 times, or greater than 5 times larger than the target region are all within the scope of this disclosure.

[0025] Turning to the drawings, FIG 1 illustrates a perspective view of an ultrasound system 100 with a head 10 of a subject and FIG. 2 is a schematic drawing of the ultrasound system 100 with the target brain region 20a in the head 10 (e.g., brain) of the subject, according to embodiments herein. The ultrasound system 100 and related methods of use described herein provide a noninvasive ultrasound-based neuromodulatory device that may be used, for example, for treatment and/or diagnosis of neurological and mental disorders. The ultrasound system 100 includes a controller 101 and two transducers 102 operably coupled to the controller and configured to selectively generate ultrasonic waves 115 at a low frequency effective to stimulate a target brain region 20a of a subject without ablating the target brain region 20a. The ultrasound system 100 may be configured to provide deep brain therapy. Moreover, embodiments of the system 100 and related methods of use may be configured to delivery ultrasonic neuromodulation for repeated use at home. The ultrasound system 100 and related methods of use do not require the conventional steps for precision targeting of a region of the brain, and thus enable in-home use of the ultrasound system 100. More particularly, the ultrasound system 100 and related methods of use may be utilized without the need for MRI images of the head or other precision neuronavigation tools. Moreover, the ultrasound system 100 and related methods of use enable repeated and reproducible use, including in in-home settings.

[0026] As used herein, “stimulation” of the target brain region (or other target regions) may include a modulation of activity of excitable cells, such as neurons, glial cells, pancreatic cells, or other cell types that are responsive to the mechanical pressure waves associated with ultrasound. As used herein, “stimulation” is broad enough to include delivery of mechanical pressure waves at any degree, energy level, or amount configured to induce a therapeutic response from the target cell

[0027] In many embodiments, the frequency of the ultrasonic waves 115 generated by the transducers 102 may be about 100 kHz to about 400 kHz, about 100 kHz to about 300 kHz, about 200 kHz to about 400 kHz, about 100 kHz to about 200 kHz, about 150 kHz to about 250 kHz, about 200 kHz to about 300 kHz, about 250 kHz to about 350 kHz, about 300 kHz to about 400 kHz, less than about 500 kHz, less than about 450 kHz, less than about 400 kHz, less than about 350 kHz, less than about 300 kHz, less than about 250 kHz, less than about 200 kHz, or less than about 150 kHz. [0028] As shown in the schematic of FIG. 2, the ultrasonic waves 115 generated by the two transducers 102 have a focal width 120 larger than the target brain region 20a in the head 10 (e g , brain) of the subject For example, the focal width 120 may be larger than the diameter of deep brain nuclei in the brain of the subject. By generating ultrasonic waves 115 having a larger focal width 120 than the target brain region 20a, the configuration of the ultrasound system 100 increases the likelihood or even ensures that the target brain region 20a is engaged by the ultrasonic waves 115 (e.g., modulated or stimulated) — even in cases without precise guidance. The relatively large focal width 120 or volume may be produced by at least one of the relatively low frequency of the ultrasonic waves 115 emitted by the transducers 102 and/or the multi-element arrays In many embodiments, the focal width 120 is at least about three millimeters In some embodiments, the focal width or volume of the transducers is about two to about three times larger than the target brain region 20a. This focal width 120 allows the target brain region 20a be stimulated or activated by the ultrasonic waves 115 even during in-home use in which precision guidance is not available. In some instances, deep brain nuclei or peripheral targets may span about 2 mm to about 5 mm. For such targets, a focal width of an ultrasound beam may be from about 2 mm to about 15 mm, including from about 6 mm to about 15 mm, from about 5 mm to about 10 mm, from about 3 mm to about 8 mm, or may be less than 20 mm, less than 15 mm, less than 10 mm, and may be greater the 3 mm, greater than 6 mm, and/or greater than 9 mm. These ranges for focal widths may be applied to any embodiment described herein.

[0029] The ultrasound system 100 may be coupled to the head 10 at multiple points or regions. For example, the transducers 102 may be secured to a head support assembly 105 configured to support the transducers 102 in a position that allows the head 10 of the subject to be disposed between the two transducers 102 The head support assembly 105 may be configured to position the head 10 and/or the transducers 102 such that the transducers provide maximal intensity of the ultrasonic waves 115 at the intended target brain region 20a In the ultrasound system 100, the head support assembly 105 includes a body 107 that is generally U-shaped, with the transducers 102 secured to opposing arms of the U-shaped body 107 (e.g., proximate to terminating end regions of the U-shaped body 107. The arms of the U-shaped body 107 and the transducers 102 are spaced from one another at a distance for the head 10 of the subject to be positioned between the transducers 102).

[0030] In many embodiments, the head support assembly 105 further comprises a base 106 and a mask 103 (e.g., radiological mask) secured to the base 106. The mask 103 is configured to position and selectively retain or stabilize the head 10 of the subject between the mask 103 and the base 106 with the head 10 also between the transducers 102. The mask 103 may comprise thermoplastic and, in some embodiments, may be molded complementary to a face of the subject and/or morph into facial features of each individual subject. The mask 103, then, may hold the head 10 in a single defined location on the base 106 to enable reproducible positioning of the head 10 from neuromodulation session to the next. Moreover, the mask 103 may prevent motion of the head 10 during operation of the ultrasound system 100 (e.g., when the transducers 102 are emitting the ultrasonic waves 115). In other words, the mask 103 may be configured to stabilize the head 10 of the subject and provide reproducible positioning of the head 10 to allow the transducers 102 to stimulate the target brain region 20a within the focal width 120 of the ultrasonic waves 115 emitted by the transducers 102.

[0031] The transducers 102 may be held in a position that focuses the ultrasonic waves 115 into the desired target brain region 20a. Accordingly, the head support assembly 105 may hold the transducers 102 in a position or orientation that aims the ultrasonic waves 115 at the selected target brain region 20a given the stabilized position of the head 10 in the head support assembly 105. Said another way, the mask 103 and the two transducers 102 may be selectively positioned by an operator or caregiver such that the brain target region 20a is within the focal width 120 of the two transducers on opposing regions of the body 107 of the head support assembly 105 when the head 10 of the subject is positioned between the radiological mask 103 and the base 106 with the head 10 also between the two transducers 102 In many embodiments, the two opposing transducers 102 are positioned such that the focal regions including the focal width 120 of each of the transducers 102 are proximate or overlapping with one another. The head support assembly 105 may be configured or adjusted such that the target brain region 20a may be positioned within this area or region where the focal regions including the focal width 120 of each of the transducers 102 overlap or are proximate to one another, as shown in FIG 2

[0032] The ultrasonic waves 115 may be delivered into the head 10 of the subject from the transducers 102 using a coupling medium 104. The coupling medium 104 may comprise any material that conducts the ultrasonic waves 115, such as a cryogel. In some embodiments, the transducers 102 are adjustably secured to the body 107 and configured to adjust to the head 10 of the subject such that the transducers 102 and/or the coupling medium 104 contact at least one of the radiological mask 103 or the head 10 of the subject. In some embodiments, the transducers 102 are selectively steerable and the controller 101 includes a steering control configured to steer the transducers 102 to direct the ultrasonic waves 115 at the brain target region 20a when the head 10 of the subject is positioned between the transducers 102. Thus, the ultrasound system 100 may provide the ability for an operator to steer the ultrasonic waves 115 into the target brain region 20a using the controller 101 (e.g., an electronic controller). In some embodiments, ultrasound aberrations by the head may be compensated for using an ultrasound through-transmit procedure described by Riis, et al. in the publication of “Controlled noninvasive modulation of deep brain regions in humans,” Communications Engineering, 3(1 ), 13 (2024), the disclosures of which are incorporated herein by this reference

[0033] The positioning of the transducers 102 allow the ultrasound system 100 and related methods of use to deliver ultrasonic waves 115 from one or more transducers 102 into specified deep brain target regions (e.g., the target brain region 20a) of the subject The targeting of the ultrasonic waves 115 into specific brain regions (e.g., the target brain region 20a) for a given condition or disorder may be mediated using fixed transducer holders (e.g., the holder assembly 105), such that the ultrasonic waves 115 are aimed specifically into the desired target brain region 20a. [0034] The controller 101 may be configured to provide voltages of specific waveforms to the transducers 102. In some embodiments, the voltages and wave forms may be defined by the required stimulation parameters for the target brain region Generally, low-intensity ultrasound should be safe and thus the stimulation parameters would ideally comply with the FDA 510k guidelines on safe ultrasound exposure, i.e., not exceeding peak intensity of 190W/cm² and not exceeding time-average intensity of 0.72 W/cm². The controller can drive either a single channel (for single-element transducer) or multiple channels (for ultrasound arrays).

[0035] The controller 101 may be configured to implement any of the example methods disclosed herein, such as the method 400 described below. Moreover, the controller 101 may be configured to coordinate or otherwise direct the transducers 102 to emit the ultrasonic waves 115 at a selected frequency The controller 101 may include at least one computing device configured to perform one or more of the acts described herein. The at least one computing device of the controller 101 can include one or more servers, one or more computers (e.g., desk-top computer, lap-top computer), or one or more mobile computing devices (e.g , smartphone, tablet, etc.). The computing device of the controller 101 can comprise at least one processor, memory, a storage device, an input/output (“I/O”) device/interface, and a communication interface. Additional or alternative components may be used in some examples. Further, in some examples, the controller 101 or the computing device can include fewer components

[0036] In some examples, the processor(s) of the controller 101 includes hardware for executing instructions (e.g., instructions for carrying out one or more portions of any of the methods disclosed herein), such as those making up a computer program For example, to execute instructions, the processor(s) may retrieve (or fetch) the instructions from an internal register, an internal cache, the memory, or a storage device and decode and execute them. In particular examples, processor(s) of the controller 101 may include one or more internal caches for data. As an example, the processor(s) of the controller 101 may include one or more instruction caches, one or more data caches, and one or more translation lookaside buffers (TLBs) Instructions in the instruction caches may be copies of instructions in memory or storage device. In some examples, the processor of the controller 101 may be configured (e g., include programming stored thereon or executed thereby) to carry out one or more portions of any of the example methods or acts disclosed herein. In some examples, the processor of the controller 101 is configured to perform any of the acts disclosed herein (such as in the method 400) or cause one or more portions of the computing device or the controller 101 to perform at least one of the acts disclosed herein. Such configuration can include one or more operational programs (e.g., computer program products) that are executable by the at least one processor of the controller 101.

[0037] The at least one computing device (e.g., a server) of the controller 101 may include at least one memory storage medium (e.g., memory and/or storage device) The computing device of the controller 101 may include memory, which is operably coupled to the processor(s) of the controller 101. The memory may be used for storing data, metadata, and programs for execution by the processor(s) The memory of the controller 101 may include one or more of volatile and non-volatile memories, such as Random Access Memory (RAM), Read-Only Memory (ROM), a solid state disk (SSD), Flash, Phase Change Memory (PCM), or other types of data storage. The memory of the controller 101 may be internal or distributed memory.

[0038] The computing device of the controller may include the storage device having storage for storing data or instructions. The storage device may be operably coupled to the at least one processor. In some examples, the storage device of the controller can comprise a non-transitory memory storage medium, such as any of those described above. The storage device (e.g., non- transitory storage medium) of the controller 101 may include a hard disk drive (HDD), a floppy disk drive, flash memory, an optical disc, a magneto-optical disc, magnetic tape, or a Universal Serial Bus (USB) drive or a combination of two or more of these The storage device of the controller 101 may include removable or non-removable (or fixed) media. The storage device of the controller 101 may be internal or external to the computing device. In some examples, the storage device of the controller 101 may include non-volatile solid-state memory. In some examples, the storage device of the controller 101 may include read-only memory (ROM). Where appropriate, this ROM may be mask-programmed ROM, programmable ROM (PROM), erasable PROM (EPROM), electrically erasable PROM (EEPROM), electrically alterable ROM (EAROM), or flash memory or a combination of two or more of these In some examples, one or more portions of the memory and/or the storage device (e.g., memory storage medium(s)) may store one or more databases thereon.

[0039] The computing device of the controller 101 also may include one or more I/O devices/interfaces, which are provided to allow a user to provide input to, receive output from, and otherwise transfer data to and from the computing device These I/O devices/interfaces of the controller 101 may include a mouse, keypad or a keyboard, a touch screen, camera, optical scanner, network interface, web-based access, modem, a port, other known I/O devices, or a combination of such I/O devices/interfaces The touch screen may be activated with a stylus or a finger. The I/O devices/interfaces of the controller 101 may include one or more devices for presenting output to a user, including, but not limited to, a graphics engine, a display (e.g., a display screen or monitor), one or more output drivers (e.g., display drivers), one or more audio speakers, and one or more audio drivers.

[0040] The computing device of the controller 101 also may include a communication interface. The communication interface may include hardware, software, or both. The communication interface of the controller 101 may provide one or more interfaces for communication (such as, for example, packet-based communication) between the computing device and one or more additional computing devices or one or more networks. For example, communication interface of the controller 101 may include a network interface controller (NIC) or network adapter for communicating with an Ethernet or other wire-based network or a wireless NIC (WNIC) or wireless adapter for communicating with a wireless network, such as a WI-FI. Any suitable network and any suitable communication interface of the controller 101 may be used. For example, the computing device of the controller 101 may communicate with an ad hoc network, a personal area network (PAN), a local area network (LAN), a wide area network (WAN), a metropolitan area network (MAN), or one or more portions of the Internet or a combination of two or more of these. One or more portions of one or more of these networks may be wired or wireless. As an example, one or more portions of controller 101 may communicate with a wireless PAN (WPAN) (such as, for example, a BLUETOOTH WPAN), a WI-FI network, a WI-MAX network, a cellular telephone network (such as, for example, a Global System for Mobile Communications (GSM) network), or other suitable wireless network or a combination thereof. The computing device of the controller

101 may include any suitable communication interface for any of these networks, where appropriate.

[0041] The computing device of the controller 101 may include a bus. The bus can include hardware, software, or both that couples components of computing device of the controller 101 to each other. For example, the bus of the controller 101 may include an Accelerated Graphics Port (AGP) or other graphics bus, an Enhanced Industry Standard Architecture (EISA) bus, a front-side bus (FSB), a HYPERTRANSPORT (HT) interconnect, an Industry Standard Architecture (ISA) bus, an INFINIBAND interconnect, a low-pin-count (LPC) bus, a memory bus, a Micro Channel Architecture (MCA) bus, a Peripheral Component Interconnect (PCI) bus, a PCI-Express (PCIe) bus, a serial advanced technology attachment (SATA) bus, a Video Electronics Standards Association local (VLB) bus, or another suitable bus or a combination thereof

[0042] Turning ahead in the drawings, FIG 3 is a side view of an ultrasound system 200 on a body 12 of a subject and FIG. 4 is a front view of the ultrasound system 200 on the body 12 of the subject, according to an embodiment. While reference is made above to an ultrasound system 100 applied to a brain target region 20a, also contemplated herein are ultrasound systems (e.g., the ultrasound system 200) configured for use with other target regions in the body 12 of the subject (e.g., the ultrasound systems disclosed herein are not limited for use with just the brain or head 10 of the subject). For example, the ultrasound system 200 and related methods of use may provide noninvasive neuromodulation that may be used, for example, for treatment and/or diagnosis of pain, inflammation, hemorrhage, insulin or glucose control, arrhythmias, or coronary heart disease. As shall be described in greater detail below, the ultrasound system 200 may be sized, dimensioned, and otherwise configured to be applied to the corresponding body part during methods of use and may utilize defined anatomical landmarks such as the rib cage, specific ribs, the xiphoid process, or the umbilicus for positioning of the transducer 202.

[0043] Unless otherwise noted or specified, the ultrasound system 200 may include any aspect of the ultrasound system 100 described above. Accordingly, like features are designated with like reference numerals with the leading digits incremented to “2.” For example, the ultrasound system 200 may include a controller 201 , a transducer 202 configured to emit ultrasonic waves 215, and a coupling medium 204 that may, in some respects, resemble the controller 101 , the transducer

102 configured to emit the ultrasonic waves 115, and the coupling medium 104 of the ultrasound system 100.

[0044] In many embodiments, the ultrasound system 200 (e.g., ultrasound-based neuromodulation system) is configured for at-home or outpatient use. The ultrasound system may comprise the controller 201 and the transducer 202 operably coupled to the controller 201 and configured to selectively generate the ultrasonic waves 215 at a low frequency (e.g., about 100 kHz to about 400 kHz) effective to stimulate the target region 20b of the body 12 of the subject without ablating the target region. The ultrasonic waves 215 generated by the transducer 202 may have a focal width 220 that is at least about 3 mm and/or larger than the target region 20b of the body 12 of the subject.

[0045] The system 200 and related methods of use allow for repeated and reproducible delivery of ultrasonic neuromodulation in outpatient clinical settings or at home. The transducer 202 of the system 200 may be positionable on multiple regions of the body 12 of the subject. More particularly, the transducer 202 of the system 200 may be placed over the target organ or structure based on defined anatomical landmarks The anatomical landmarks may be used to create markers on the skin of the subject to guide the placement of the ultrasonic transducer 202. Similar to the ultrasound system 100, the focal width 220 or volume of the ultrasonic waves 215 activated by the transducer 202 is larger than the width or volume of the target region 20b, which ensures that the target region 20b is modulated in cases in which precision imaging guidance is not available. This approach using the ultrasound system 200 ensures reproducible stimulation of the desired target region(s) across sessions in outpatient settings or at home. The ultrasound system 200 and related methods of use circumvent the need for precision targeting and thus enable use of the ultrasound system 200 in outpatient clinical settings or at home. The ultrasound system 200 and related methods of use can be utilized without the need for taking MRI, ultrasound, CT, or other precision neuronavigation tools. In addition, the ultrasound system 200 and related methods of use enable repeated and reproducible use, including in outpatient clinical settings or at home. [0046] The transducer 202 is configured to stimulate the targeted region 20b with a relatively large stimulation volume from the larger focal width 220 or volume of ultrasonic waves 215 or beam emitted by the transducer 202. The relatively large stimulation volume of the ultrasonic waves 214 may be produced by an unfocused ultrasound transducer 202, by an ultrasound transducer 202 with a large aperture, by a low carrier frequency of the emitted ultrasound, or combinations thereof. As also noted above, “stimulation” is broad enough to include delivery of mechanical pressure waves at any degree, energy level, or amount configured to induce a therapeutic response from the target cell. In many embodiments, the transducer 202 may be configured to emit ultrasonic waves 215 at any of the frequencies described above in relation to the transducers 102.

[0047] As shown in the schematic of FIG. 3, the ultrasonic waves 215 or beam generated by the transducer 202 have a focal width 220 or volume larger than the target region 20b in the head 12 of the subject. In some embodiments, the transducer 202 includes a wave emitting region from which the ultrasonic waves 215 are emitted from the transducer 202. The wave emitting region of the transducer 202 may have an area substantially equal to or larger than the target region 20b such that the beam of ultrasonic waves 215 is at least equal to or larger than the target region 20b. Thus, the beam including the ultrasonic waves 215 of the emitted ultrasound energy has a diameter that is comparable to or larger than the diameter of the target region 20b to be stimulated by the ultrasonic waves. This way, the desired target region 20b will be stimulated even under small errors in targeting. This application of the ultrasonic waves 215 with the transducer 202 may maximize treatment effectiveness and practicality. Any of the size ranges for ultrasound focal size recited above may also be applied to this, or any other embodiment described herein The ultrasonic waves 215 may be propagated into the target region 20b using a standard ultrasound coupling medium 204, such as ultrasound gel or silicone.

[0048] Turning specifically to FIG. 4, the transducer 202 may be secured to a body strap 212 configured to wrap around a portion of the body 12 to position the transducer 202 over the target region 20b. For stimulation periods greater than a predetermined time (e.g., 5 minutes), the transducer 202 may be secured to the body 12 with the body strap 212 The body strap 212 may be used to secure the transducer 202 to the body 12 for stimulations of any duration

[0049] In some embodiments, the subject or a caregiver may place the ultrasonic transducer 202 on the body 12 based on previously made markers 14a, 14b on the skin of the subject. In some embodiments, the transducer 202 includes guidance tips 211a, 211 b or other alignment features positioned to align with the markers 14a, 14b previously made on the skin of the subject. The markers 14a, 14b may be at least somewhat permanent (e.g., lasting more than one week or one month) or permanent. For example, the markers 14a, 14b may include a skin tattoo. The markers 14a, 14b may comprise one or more small dots on the skin of the subject. The subject or a caregiver may align the tips 211 a, 211 b with the markers 14a, 14b on the skin of the subject to position the transducer 202 in the appropriate spot for stimulation of the target region 20b This practical positioning, which may initially be marked by a physician or a physician assistant, allows the ultrasound system 200 to deliver the neuromodulation from the ultrasonic transducer 202 into a specified body region. Positioning of the markers 14a, 14b may be made on the skin based on localization of particular target regions 20b, described in greater detail below.

[0050] The controller 201 may be configured to provide voltages of specific waveforms to the transducer 202. In some embodiments, the voltages and wave forms may be defined by the required stimulation parameters for the target region 20b.

[0051] In many embodiments, the same ultrasound system 200 and/or transducer 202 may be applied to different target regions 20b of the body 12 at different times In some embodiments, the target region 20b includes a target spleen region on or in the spleen of the subject To stimulate the target spleen region, the transducer 202 may be positioned behind ribs 9 and 11 on a left side of the body 12 of the subject. Activating the transducer 202 to emit or generate the ultrasonic waves 215 may stimulate the target spleen region to at least partially treat one or more of inflammation of spleen inflammation, acute kidney injury, and/or hemorrhaging in the subject without ablating the target spleen region.

[0052] In some embodiments, the target region 20b includes a target liver region on or in the liver of the subject. To stimulate the target liver region, the transducer 202 may be positioned under a rib cage below a xiphoid process on the body 12 of the subject. Activating the transducer 202 to emit or generate the ultrasonic waves 215 may stimulate the target liver region to at least partially control a glucose level of the subject without ablating the target liver region. [0053] In some embodiments, the target region 20b includes a target pancreas region on or in the pancreas of the subject. To stimulate the target pancreas region, the transducer 202 may be positioned a back of an abdominal cavity of the body 12 of the subject approximately three to approximately six inches above an umbilicus of the subject. Activating the transducer 202 to emit or generate the ultrasonic waves 215 may stimulate the target pancreas region to at least partially control release of insulin of the subject without ablating the target pancreas region.

[0054] In some embodiments, the target region 20b includes a target heart region on or in the heart of the subject. To stimulate the target heart region, the transducer 202 may be positioned left of the sternum of the subject between the junction of ribs 4 and 5 of the subject. Activating the transducer to emit or generate the ultrasonic waves 215 may stimulate the target heart region to at least partially treat one or more of coronary heart disease and/or arrhythmia of the subject without ablating the target heart region.

[0055] In some embodiments, the target region 20b includes a target dorsal root ganglion region in the subject. To stimulate the target dorsal root ganglion region, the transducer 202 may be positioned near the midline between pairs of ribs on the back of the subject. Activating the transducer to emit or generate the ultrasonic waves 215 may stimulate the target dorsal root ganglion region to at least partially treat pain of the subject without ablating the target dorsal root ganglion region.

[0056] In some embodiments, the target region 20b includes a target nerve region of peripheral nerves in the subject. To stimulate the target nerve region, the transducer 202 may be positioned over nerves of the subject. This positioning may be at least partially based on ultrasound images. Activating the transducer to emit or generate the ultrasonic waves 215 may stimulate the target nerve region to at least partially treat pain of the subject without ablating the target nerve region. [0057] T urning ahead in the drawings, FIG. 5 is a flow diagram of a method 500 of stimulating a target region of a body of a subject, according to embodiments disclosed herein. The method 500 may utilize any of the ultrasound systems 100, 200 disclosed herein. In many embodiments, the method 500 comprises positioning 505 one or more transducers of an ultrasound system on the subject at least proximate to the target region and, with a controller coupled to the one or more transducers, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject. In the method 500, the ultrasonic waves generated by the one or more transducers may have a focal width that is at least about three millimeters and/or larger than the target region of the body of the subject.

[0058] Activating 510 the one or more transducers to generate the ultrasonic waves may comprise activating the one or more transducers to generate the ultrasonic waves for a duration of a least five seconds. The stimulation may be repeated several (10-100) times during a single session and repeated over multiple sessions, which can proceed daily or separated by a period of days or weeks.

[0059] In some embodiments, the method 500 may include use of the ultrasound system 100. In these and other embodiments of the method 500, the one or more transducers may comprise two transducers secured to a body of a head support assembly; the target region may comprise a target brain region, and positioning 505 one or more transducers of an ultrasound system on the subject at least proximate to the target region may comprise positioning a head of the subject between the two transducers with the target brain region between the two transducers.

[0060] In some embodiments of the method 500, the head support assembly further comprises a base and a radiological mask secured to the base. Positioning 505 a head of the subject between the two transducers with the target brain region between the two transducers may then comprise positioning the head of the subject between the radiological mask and the base with the head also between the two transducers The radiological mask may comprise thermoplastic and is molded complementary to a face of the subject or contours to the face of the subject In some embodiments, the method 500 further comprises adjusting the two transducers to the head of the subject such that the transducers contact at least one of the radiological mask or the head of the subject. The radiological mask and the two transducers may be selectively positioned such that the brain target region is within the focal width of the two transducers

[0061] In some embodiments, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz comprises activating the two transducers to generate the ultrasonic waves at a frequency of about 200 kHz to about 400 kHz to activate tissue in the target brain region without ablating the tissue in the brain The method 500 may further comprise, with a steering controller on the controller, steering the two transducers to direct the ultrasonic wave at the brain target region.

[0062] In some embodiments, the method 500 may include use of the ultrasound system 200. In these and other embodiments of the method 500, the one or more transducers comprise one transducer and positioning 505 one or more transducers of an ultrasound system on the subject at least proximate to the target region comprises positioning 505 the one transducer on a selected region of the body of the subject. The one transducer may comprise a wave emitting region from which the ultrasonic waves are emitted from the one transducer, with the wave emitting region having an area substantially equal to or larger than the target region. In some embodiments of the method 500, positioning 505 the one transducer on a selected region of the body of the subject comprises positioning the one transducer on a selected region of the body of the subject by aligning the one transducer with one or more markers on skin of the subject.

[0063] In some embodiments of the method 500, positioning 505 the one transducer on a selected region of the body of the subject comprises positioning 505 the one transducer behind ribs 9 and 11 on a left side of the body of the subject, with the target region comprising a target spleen region of the subject. In these and other embodiments of the method 500, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject may comprise activating 510 the one transducer effective to stimulate the target spleen region to at least partially treat one or more of inflammation of spleen inflammation, acute kidney injury, and/or hemorrhaging in the subject without ablating the target spleen region [0064] In some embodiments of the method 500, positioning 505 the one transducer on a selected region of the body of the subject comprises positioning the one transducer under a rib cage below a xiphoid process on the body of the subject, the target region comprising a target liver region of the subject In these and other embodiments of the method 500, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject may comprise activating 510 the one transducer effective to stimulate the target liver region to at least partially control a glucose level of the subject without ablating the target liver region.

[0065] In some embodiments of the method 500, positioning 505 the one transducer on a selected region of the body of the subject comprises positioning the one transducer on a back of an abdominal cavity of the body of the subject approximately three to approximately six inches above an umbilicus of the subject, the target region comprising a target pancreas region of the subject. In these and other embodiments of the method 500, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject may comprises activating 510 the one transducer effective to stimulate the target pancreas region to at least partially control release of insulin of the subject without ablating the target pancreas region.

[0066] In some embodiments of the method 500, positioning 505 the one transducer on a selected region of the body of the subject comprises positioning the one transducer left of a sternum of the subject between a junction of ribs 4 and 5 of the subject, the target region comprising a target heart region of the subject. In these and other embodiments of the method 500, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject may comprise activating 510 the one transducer effective to stimulate the target heart region to at least partially treat one or more of coronary heart disease and/or arrhythmia of the subject without ablating the target heart region.

[0067] In some embodiments of the method 500, positioning 505 the one transducer on a selected region of the body of the subject comprises positioning the one transducer near a midline between pairs of ribs on a back of the subject, the target region comprising a target dorsal root ganglion region of the subject. In these and other embodiments of the method 500, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject comprises activating 510 the one transducer effective to stimulate the target dorsal root ganglion region to at least partially treat pain of the subject without ablating the target dorsal root ganglion region.

[0068] In some embodiments of the method 500, positioning 505 the one transducer on a selected region of the body of the subject comprises positioning the one transducer over nerves of the subject, with the target region comprising a target nerve region of the subject In these and other embodiments of the method 500, activating 510 the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject may comprise activating 510 the one transducer effective to stimulate the target nerve region to at least partially treat pain of the subject without ablating the target nerve region.

[0069] Any methods disclosed herein comprise one or more steps or actions for performing the described method. The method steps and/or actions may be interchanged with one another. In other words, unless a specific order of steps or actions is required for proper operation of the embodiment, the order and/or use of specific steps and/or actions may be modified.

[0070] FIGS. 6A-6D illustrate a wearable ultrasound system 300. One of skill in the art, having the benefit of this disclosure, will recognize that any of the preceding disclosure, relating the ultrasound systems 100 and 200 as well as the methods disclosed above may be applied and/or adapted to the embodiment of FIGS. 6A-6D. The ultrasound system 300 is shown positioned on the head 30 of a subject. The ultrasound system may comprise one or ultrasound transducers 302 configured to delivery ultrasound energy to the head 30 of the subject. Additionally, the ultrasound system 300 may comprise one or more mounting locations 308 configured to contact the head 30 of the subject and secure or couple the ultrasound system 300 to the head 30. In some embodiments, the mounting locations 308 may comprise adjustable bands, pad, straps, hooks, and so forth. Additionally or alternatively, the mounting locations 308 may be configured to rest on, couple to, or otherwise interact with one or more features of the head 30, such as the nose, ears, temples, crown, and so forth.

[0071] A wearable system, such as ultrasound system 300 may be used in connection with any of the concepts or methods disclosed herein. For example, ultrasound system 300 may be configured such that the focal width is larger than the target region of the body. The larger focal width correlates to a larger tolerance when targeting a specific target region of the head 30 for stimulation. This tolerance may, in turn, facilitate use of a wearable system, such as ultrasound system 300.

[0072] A wearable system, such as ultrasound system 300, may be positioned at different positions on the head 30 during different treatment sessions and/or may slip or shift during treatment, due to the nature of the device. However, the degree of tolerance around the target region provided by the larger focal width, may enable a wearable device to effectively treat the target region, without requiring perfect or near perfect placement of the wearable device each time This may facilitate use of a wearable device, such as ultrasound system 300 in outpatient settings, at home, or other locations. Additionally or alternatively, such a system may allow a user to begin and end treatment individually and may be configured for use during other activities such as watching television or reading.

[0073] The flexibility and adaptability of a wearable system, such as ultrasound system 300, when configured with a focal width larger than the target zone, may thus provide for more comfortable and more frequent use [0074] References to approximations are made throughout this specification, such as by use of the term “substantially.” For each such reference, it is to be understood that, in some embodiments, the value, feature, or characteristic may be specified without approximation For example, where qualifiers such as “about” and “substantially” are used, these terms include within their scope the qualified words in the absence of their qualifiers.

[0075] Similarly, in the above description of embodiments, various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure. This method of disclosure, however, is not to be interpreted as reflecting an intention that any claim require more features than those expressly recited in that claim Rather, as the following claims reflect, inventive aspects lie in a combination of fewer than all features of any single foregoing disclosed embodiment

[0076] The claims following this written disclosure are hereby expressly incorporated into the present written disclosure, with each claim standing on its own as a separate embodiment This disclosure includes all permutations of the independent claims with their dependent claims. Moreover, additional embodiments capable of derivation from the independent and dependent claims that follow are also expressly incorporated into the present written description.

[0077] Without further elaboration, it is believed that one skilled in the art can use the preceding description to utilize the invention to its fullest extent. The claims and embodiments disclosed herein are to be construed as merely illustrative and exemplary, and not a limitation of the scope of the present disclosure in any way. It will be apparent to those having ordinary skill in the art, with the aid of the present disclosure, that changes may be made to the details of the abovedescribed embodiments without departing from the underlying principles of the disclosure herein. In other words, various modifications and improvements of the embodiments specifically disclosed in the description above are within the scope of the appended claims Moreover, the order of the steps or actions of the methods disclosed herein may be changed by those skilled in the art without departing from the scope of the present disclosure In other words, unless a specific order of steps or actions is required for proper operation of the embodiment, the order or use of specific steps or actions may be modified. The scope of the invention is therefore defined by the following claims and their equivalents.

Claims

1. An ultrasound system for at-home use, the ultrasound system comprising: a controller; and one or more transducers operably coupled to the controller and configured to selectively generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate a target region of a body of a subject without ablating the target region, the ultrasonic waves generated by the one or more transducers having a focal width that is at least two times larger than the target region of the body of the subject.

2. The ultrasound system of claim 1 , wherein the focal width is at least about three millimeters.

3. The ultrasound system of either claim 1 or claim 2, further comprising a head support assembly comprising a body, wherein the one or more transducers comprise two transducers secured to the body and spaced from one another at a distance for a head of the subject to be positioned between the two transducers, the target region comprising a target brain region.

4. The ultrasound system of claim 3, wherein the head support assembly further comprises a base and a radiological mask secured to the base and configured to position the head of the subject between the radiological mask and the base with the head also between the two transducers.

5. The ultrasound system of claim 4, wherein the radiological mask comprises thermoplastic and is molded complementary to a face of the subject or is configured to contour to the face of the subject.

6. The ultrasound system of either claim 4 or claim 5, wherein the transducers are adjustably secured to the body and configured to adjust to the head of the subject such that the transducers contact the head of the subject.

7. The ultrasound system of any one of claims 4-6, wherein the radiological mask and the two transducers are selectively positioned such that the brain target region is within the focal width of the two transducers when the head of the subject is positioned between the radiological mask and the base with the head also between the two transducers.

8. The ultrasound system of any one of claims 3-7, wherein the two transducers are configured to selectively generate ultrasonic waves at a frequency of about 200 kHz to about 400 kHz effective activate tissue in the target brain region without ablating the tissue in the brain.

9. The ultrasound system of any one of claims 3-8, wherein the two transducers are selectively steerable and the controller includes a steering control configured to steer the two transducers to direct the ultrasonic waves at the brain target region when the head of the subject is positioned between the two transducers.

10. The ultrasound system of claim 1 , wherein the one or more transducers are positionable on one or multiple regions of the body of the subject

11 . The ultrasound system of claim 10, wherein the one transducer is positionable behind ribs of the subject and the target region includes a target spleen region of the subject, the one transducer being configured to generate the ultrasonic waves effective to stimulate the target spleen region to at least partially treat one or more of inflammation of spleen inflammation, acute kidney injury, and/or hemorrhaging in the subject without ablating the target spleen region.

12. The ultrasound system of claim 10, wherein the one transducer is positionable under a rib cage below a xiphoid process of the subject and the target region includes a target liver region of the subject, the one transducer being configured to generate the ultrasonic waves effective to stimulate the target liver region to at least partially control a glucose level of the subject without ablating the target liver region.

13. The ultrasound system of claim 10, wherein the one transducer is positionable on a back of an abdominal cavity of the subject and the target region includes a target pancreas region of the subject, the one transducer being configured to generate the ultrasonic waves effective to stimulate the target pancreas region to at least partially control release of insulin of the subject without ablating the target pancreas region.

14. The ultrasound system of claim 10, wherein the one transducer is positionable on ribs of the subject and the target region includes a target heart region of the subject, the one transducer being configured to generate the ultrasonic waves effective to stimulate the target heart region to at least partially treat one or more of coronary heart disease and/or arrhythmia of the subject without ablating the target heart region.

15. The ultrasound system of claim 10, wherein the one transducer is positionable on ribs of the subject and the target region includes a target dorsal root ganglion region of the subject, the one transducer being configured to generate the ultrasonic waves effective to stimulate the target dorsal root ganglion region to at least partially treat pain of the subject without ablating the target dorsal root ganglion region.

16. The ultrasound system of claim 10, wherein the one transducer is positionable over a target nerve region of the subject, the one transducer being configured to generate the ultrasonic waves effective to stimulate the target nerve region to at least partially treat pain of the subject without ablating the target nerve region

17. The ultrasound system of any one of claims 10-16, wherein the one transducer includes a wave emitting region from which the ultrasonic waves are emitted from the one transducer, the wave emitting region having an area substantially equal to or larger than the target region.

18. The ultrasound system of any one of claims 1-17, wherein the ultrasound system comprises a wearable device.

19. The ultrasound system of claim 18, wherein the ultrasound system is configured to be placed on the head of a patient and rest on one or more features of the head of the patient.

20. A method of stimulating a target region of a body of a subject, the method comprising: positioning one or more transducers of an ultrasound system on the subject at least proximate to the target region; and with a controller coupled to the one or more transducers, activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject, the ultrasonic waves generated by the one or more transducers having a focal width that is at least two times larger than the target region of the body of the subject.

21 . The method of claim 20, wherein the focal width is at least about three millimeters.

22. The method of either claim 20 or claim 21 , wherein: the one or more transducers comprise two transducers secured to a body of a head support assembly; the target region includes a target brain region; and positioning one or more transducers of an ultrasound system on the subject at least proximate to the target region comprises positioning a head of the subject between the two transducers with the target brain region between the two transducers.

23. The method of claim 22, wherein: the head support assembly further comprises a base and a radiological mask secured to the base; positioning a head of the subject between the two transducers with the target brain region between the two transducers comprises positioning the head of the subject between the radiological mask and the base with the head also between the two transducers.

24. The method of claim 20, wherein the radiological mask comprises thermoplastic and is molded complementary to a face of the subject or contours to the face of the subject.

25. The method of either claim 23 or claim 24, further comprising adjusting the two transducers to the head of the subject such that the transducers the head of the subject

26. The method of any one of claims 23-25, wherein the radiological mask and the two transducers are selectively positioned such that the brain target region is within the focal width of the two transducers.

27. The method of any one of claims 20-26, wherein activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz comprises activating the two transducers to generate the ultrasonic waves at a frequency of about 200 kHz to about 400 kHz to activate tissue in the target brain region without ablating the tissue in the brain.

28. The method of any one of claims 20-27, further comprising, with a steering controller on the controller, steering the two transducers to direct the ultrasonic wave at the brain target region.

29. The method of claim 20, wherein: the one or more transducers comprise one transducer; and wherein positioning one or more transducers of an ultrasound system on the subject at least proximate to the target region comprises positioning the one transducer on a selected region of the body of the subject.

30. The method of claim 29, wherein: positioning the one transducer on a selected region of the body of the subject comprises positioning the one transducer behind ribs 9 and 11 on a left side of the body of the subject, the target region comprising a target spleen region of the subject; and activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject comprises activating the one transducer effective to stimulate the target spleen region to at least partially treat one or more of inflammation of spleen inflammation, acute kidney injury, and/or hemorrhaging in the subject without ablating the target spleen region.

31 . The method of claim 29, wherein: positioning the one transducer on a selected region of the body of the subject comprises positioning the one transducer under a rib cage below a xiphoid process on the body of the subject, the target region comprising a target liver region of the subject; and activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject comprises activating the one transducer effective to stimulate the target liver region to at least partially control a glucose level of the subject without ablating the target liver region.

32. The method of claim 29, wherein: positioning the one transducer on a selected region of the body of the subject comprises positioning the one transducer on a back of an abdominal cavity of the body of the subject approximately three to approximately six inches above an umbilicus of the subject, the target region comprising a target pancreas region of the subject; and activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject comprises activating the one transducer effective to stimulate the target pancreas region to at least partially control release of insulin of the subject without ablating the target pancreas region.

33. The method of claim 29, wherein: positioning the one transducer on a selected region of the body of the subject comprises positioning the one transducer left of a sternum of the subject between a junction of ribs 4 and 5 of the subject, the target region comprising a target heart region of the subject; and activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject comprises activating the one transducer effective to stimulate the target heart region to at least partially treat one or more of coronary heart disease and/or arrhythmia of the subject without ablating the target heart region.

34. The method of claim 29, wherein: positioning the one transducer on a selected region of the body of the subject comprises positioning the one transducer near a midline between pairs of ribs on a back of the subject, the target region comprising a target dorsal root ganglion region of the subject; and activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject comprises activating the one transducer effective to stimulate the target dorsal root ganglion region to at least partially treat pain of the subject without ablating the target dorsal root ganglion region.

35. The method of claim 29, wherein: positioning the one transducer on a selected region of the body of the subject comprises positioning the one transducer over nerves of the subject, the target region comprising a target nerve region of the subject; and activating the one or more transducers to generate ultrasonic waves at a frequency of about 100 kHz to about 400 kHz effective to stimulate the target region of a body of the subject without ablating the target region of the body of the subject comprises activating the one transducer effective to stimulate the target nerve region to at least partially treat pain of the subject without ablating the target nerve region

36. The method of any one of claims 29-35, wherein the one transducer includes a wave emitting region from which the ultrasonic waves are emitted from the one transducer, the wave emitting region having an area substantially equal to or larger than the target region.

37. The method of any one of claims 29-36, wherein positioning the one transducer on a selected region of the body of the subject comprises positioning the one transducer on a selected region of the body of the subject by aligning the one transducer with one or more markers on skin of the subject.