Wearable neuromodulation devices, and related systems and methods

Abstract

Ultrasound systems for at-home use and methods of using the ultrasound systems to treat various conditions on a subject are discussed herein. A wearable ultrasound device includes two transducers coupled or configured to operably couple to a controller and configured to selectively generate ultrasonic waves. The wearable ultrasound device also includes a head support assembly having the two transducers secured thereto and configured to support the two transducers on a head of the subject with the head of the subject positioned between the two transducers. The head support assembly includes a first member positioned to extend across a forehead of a subject and one or more members configured to rest on an anatomical feature of the head. The head support assembly is configured position the two transducers on the head of the subject to deliver ultrasonic waves at a target region in a brain without ablating the target region.

Description

Docket No. P329919 WO.01WEARABLE NEUROMODULATION DEVICES, AND RELATED SYSTEMS AND METHODSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Patent Application No. 63 / 684,303 filed on August 16, 2024 and titled “Systems and Methods for Applying Ultrasonic Neuromodulation Repeatedly and Reproducibly in Outpatient Settings and at Home” and to United States Provisional Patent Application No. 63 / 772,516 filed on March 15, 2025 and titled “Methods and Wearable Systems for Applying Ultrasonic Neuromodulation Repeatedly and Reproducibly 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 in the human brain for repeated and reproducible use in outpatient settings or at home.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 is a schematic drawing of an ultrasound system with a target region in a head of a subject, according to embodiments herein.

[0005] FIG. 2A is a front view of a wearable ultrasound device being worn by a subject, according to embodiments herein

[0006] FIG. 2B is an isometric top front view of the wearable ultrasound device of FIG. 2B.

[0007] FIG. 2C is a top view of the wearable ultrasound device of FIG. 2A.

[0008] FIG. 3A is a side view of a wearable ultrasound device being worn by a subject, according to embodiments herein.

[0009] FIG. 3B is an isometric top rear view of the wearable ultrasound device of FIG 3A

[0010] FIG. 4 is a flow diagram of a method of stimulating a target region of a brain of a subject DETAILED DESCRIPTION

[0011] 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.14932-2944-1879' 1Docket No. P329919 WO.01

[0012] 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

[0013] 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.

[0014] 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.

[0015] 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.

[0016] 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 a 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 can lead to the desired target being missed, which would compromise the effectiveness and robustness of the neuromodulation. In contrast, the methods24932-2944-1879' 1Docket No. P329919 WO.01 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.

[0017] Embodiments disclosed herein may provide noninvasive ultrasound-based neuromodulatory devices, systems, and / or methods that may be used, for example, in the treatment and / or diagnosis of neurological and mental disorders. Many embodiments comprise or otherwise utilize a device that is attached or configured to be attached to the head of a subject at one or more anatomical landmarks. This positioning of the device allows the device to deliver ultrasonic waves from one or a plurality of transducers secured to the device into one or more specified deep brain targets in the brain of the subject The targeting of the ultrasound into specific brain regions for a given condition or disorder may be mediated using fixed transducer holders such that the ultrasound is aimed specifically into the desired brain regions.

[0018] In many embodiments, a wearable ultrasound device comprises two transducers coupled or configured to operably couple to a controller and configured to selectively generate ultrasonic waves. The wearable ultrasound device also comprises a head support assembly having the two transducers secured thereto and configured to support the two transducers on a head of the subject with the head of the subject positioned between the two transducers. The head support assembly may include at least a first member positioned to extend across a forehead of a subject and one or more members configured to rest on an anatomical feature of the head (e.gr, at least one of a nose or an ear of the subject) The head support assembly may be configured position the two transducers on the head of the subject to deliver ultrasonic waves at a target region in a brain of the subject without ablating the target region.

[0019] In many embodiments, a method of stimulating a target region of a brain of a subject and / or a method of treating a condition of a brain of a subject is disclosed. The method(s) may comprise providing a wearable ultrasound device comprising two transducers and a head support assembly having the two transducers secured thereto. The method(s) also may comprise positioning the two transducers of the wearable ultrasound device on a head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject. The method(s) also may comprise supporting the two transducers in a selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device The method(s) also may comprise, with a controller coupled to the two transducers, activating the two transducers to generate ultrasonic waves effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject.

[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.34932-2944-1879' 1Docket No. P329919 WO.01

[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] T urning to the drawings, FIG. 1 is a schematic drawing of a wearable ultrasound device 100 (e.gr, wearable neuromodulation device) positioned on a head 10 of a subject and to target a target region 20a in the head 10 of a subject, according to embodiments herein The ultrasound device 100 may be operably coupled to a controller 101 in an ultrasound system (e.g., ultrasoundbased neuromodulation system) for at-home or outpatient use. With the transducers 102 of the ultrasound device 100 and the controller 101 , the ultrasound system may be configured to selectively generate ultrasonic waves 115 at a low frequency (e.g. , about 200 kHz to about 400 kHz) effective to stimulate the target region 20a in the brain of the subject without ablating the target region 20a. The ultrasonic waves 115 generated by the transducers 102 have a focal width 120 that is at least about three millimeters and / or larger than the target region 20a in the brain of the subject. In some embodiments, the focal width 120 may be determined solely in relation to the size of the target area 20a, embodiments where there is no absolute minimize size of the focal width are within the scope of this disclosure For example, the focal width 120 may be at least two times larger than the target region 20a, regardless of the absolute size of the focal width 120. 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] The ultrasound device 100 comprises a head support 103 having the two transducers 102 secured thereto and configured to support the two transducers 102 on the head 10 of the subject with the head 10 of the subject positioned between the two transducers 102, according to embodiments. The head support 103 may include at least a first member positioned to extend across a forehead of the subject and one or more members configured to rest on at least one of a nose or an ear of the subject. The head support 103 is configured position the two transducers 102 on the head 10 of the subject to deliver the ultrasonic waves 115 at the target region 20a in a brain of the subject without ablating the target region 20a.44932-2944-1879' 1Docket No. P329919 WO.01

[0026] The ultrasound device 100 may be configured to provide deep brain therapy. Moreover, embodiments of the ultrasound device 100 and related methods of use may be configured to deliver ultrasonic neuromodulation for repeated use at home The ultrasound device 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 device 100. More particularly, the ultrasound device 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 device 100 and related methods of use enable repeated and reproducible use, including in in-home settings.

[0027] 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

[0028] 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.

[0029] As shown in the schematic of FIG. 1 , 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.54932-2944-1879' 1Docket No. P329919 WO.01

[0030] The ultrasound device 100 may be coupled to the head 10 at multiple points or regions. For example, the transducers 102 may be secured to the head support 103 that is 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 103 may be configured to position the head 10 and / or the transducers 102 such that the transducers 102 provide maximal intensity of the ultrasonic waves 115 at the intended target brain region 20a.

[0031] The transducers 102 may be held by the head support 103 in a position that focuses the ultrasonic waves 1 15 into the desired target brain region 20a. Accordingly, the head support 103 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 103 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 103 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. 1.

[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 described in greater detail below, the transducers 102 are configured to adjust to the head 10 of the subject such that the transducers 102 and / or the coupling medium 104 contact 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 device 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) coupled to the ultrasound device 100. 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 device 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] An ultrasound system of this disclosure comprising the ultrasound device 100 coupled to the controller 101 may be configured to treat a variety of conditions or disorders in the brain. In64932-2944-1879' 1Docket No. P329919 WO.01 some embodiments, an ultrasound system of this disclosure may be configured to treat a condition of the brain including at least one of cognitive decline or Alzheimer’s disease, and the target region 20a may include one or more of a region of the brain associated with memory functions, a hippocampus of the brain, an entorhinal cortex of the brain, an amygdala of the brain, or a nucleus basalis of Meynert of the brain In some embodiments, an ultrasound system of this disclosure may be configured to treat a condition of the brain including depression, and the target region 20a may include one or more of a cingulate cortex of the brain or a subcallosal cingulate cortex of the brain. In some embodiments, an ultrasound system of this disclosure may be configured to treat a condition of the brain including chronic pain, and the target region 20a may include one or more of an anterior cingulate cortex of the brain, a medial cingulate cortex of the brain, a subcallosal cingulate cortex, a ventral posterolateral nucleus, or a ventral posteromedial nucleus. In some embodiments, an ultrasound system of this disclosure may be configured to treat a condition of the brain including addiction, and the target region 20a may include one or more of a nucleus accumbens of the brain, a subcallosal cingulate cortex of the brain, or an anterior cingulate cortex of the brain In some embodiments, an ultrasound system of this disclosure may be configured to treat a condition of the brain including food cravings, and the target region 20a may include one or more of a nucleus accumbens of the brain or a nucleus accumbens shell of the brain. In some embodiments, an ultrasound system of this disclosure may be configured to treat a condition of the brain including anxiety, and the target region 20a may include one or more of an amygdala of the brain or a stria terminalis of the brain. In some embodiments, an ultrasound system of this disclosure may be configured to treat a condition of the brain including post-traumatic brain disorder, and the target region 20a may include one or more of an amygdala of the brain or a bed nucleus of a stria terminalis of the brain

[0035] 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 / cm2and not exceeding time-average intensity of 0.72 W / cm2. The controller 101 can drive either a single channel (for single-element transducer) or multiple channels (for ultrasound arrays)

[0036] 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 or74932-2944-1879' 1Docket No. P329919 WO.01 alternative components may be used in some examples. Further, in some examples, the controller 101 or the computing device can include fewer components.

[0037] 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.

[0038] 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.

[0039] 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),84932-2944-1879' 1Docket No. P329919 WO.01 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.

[0040] 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.

[0041] 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

[0042] 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)94932-2944-1879' 1Docket No. P329919 WO.01 bus, a serial advanced technology attachment (SATA) bus, a Video Electronics Standards Association local (VLB) bus, or another suitable bus or a combination thereof.

[0043] Turning ahead in the drawings, FIG 2A is a front view of a wearable ultrasound device 200 being worn by a subject, FIG. 2B is an isometric top front view of the wearable ultrasound device 200, and FIG. 2C is a top view of the wearable ultrasound device 200, according to embodiments. The ultrasound device 200 is configured to be use in systems and methods that allow for reproducible positioning of the ultrasound device 200 with respect to the head 10. For example, the ultrasound device 200 may include a head support assembly 203 comprising a first member 205 and an eyeglasses frame 207 secured to the first member 205. The head support assembly 203 allows the ultrasound device 200 to be fitted on the head 10 of the subject while providing reproducible positioning of the ultrasound device 200 (e.g., the transducers 202a, 202b) on the head 10 of subject(s) across multiple treatment sessions and / or multiple subjects. The ultrasound device 200, using the head support assembly 203, positions the ultrasonic transducers 202a, 202b ultrasonic transducers to aim the ultrasonic waves 115 (shown in FIG. 1 ) into the desired brain target region 20a (shown in FIG 1 ) for each specific indication (e.g. , brain condition or disorder).

[0044] 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 head support assembly 203, one or more transducers 202a, 202b secured to the head support assembly 203 and configured to emit ultrasonic waves, and a coupling medium 204 that may, in some respects, resemble the controller 101 , the head support 103, the transducer 102 secured to the head support 103 and configured to emit the ultrasonic waves 115, and the coupling medium 104 of the ultrasound system 100.

[0045] The ultrasound device 200 comprises the head support assembly 203 having the two transducers 202a, 202b secured thereto and configured to support the two transducers 202a, 202b on the head 10 of the subject with the head of the subject positioned between the two transducers 202a, 202b, according to embodiments. The head support assembly 203 may comprise a first member 205 positioned to extend across the forehead of the subject and the eyeglasses frame 207 configured to rest on at least one of a nose 12 or an ear of the subject. The head support assembly 203 is configured position the two transducers 202a, 202b on the head of the subject to deliver ultrasonic waves at a target region in the brain of the subject without ablating the target region. The first member 205 may be shaped to wrap at least partially around the forehead of the subject. For example, the first member 205 may be generally U-shaped or C-shaped. In some embodiments, the first member 205 may be configured to adjust to the head 10 of the subject. For example, the first member 205 may be configured to bend and then retain the shape to which the first member 205 is bent around the forehead of the subject. In some embodiments, the transducers 202a, 202b are secured to opposing end regions of the first member 205.

[0046] In some embodiments, the head support assembly 203 further comprises an arm 212 secured to the first member 205 and the eyeglasses frame 207 effective to secure the eyeglasses104932-2944-1879' 1Docket No. P329919 WO.01 frame 207 to the first member 205. At least one of the eyeglasses frame 207 or the first member 205 may be adjustably secured to the arm 212 to allow the subject or other individual to adjust the ultrasound device 200 to the fit the head 10 of the subject.

[0047] The eyeglasses frame 207 may comprise at least one (e.g., both) of a nasal support member 209 configured to rest on the nose 12 of the subject and one or more ear support members 211 configured to rest on one or more ears of the subject effective to support the wearable ultrasound device 200 in a selected position on the head 10 of the subject. The nasal support member 209 may comprise, for example, nose pads or nose pieces secured to the eyeglasses frame 207. In some embodiments, the nasal support member 209 is adjustably secured to the eyeglasses frame 207 to allow repositioning of the eyeglasses frame 207 in a particular position on the head 10 of the subject dependent on the selected target region in the brain of the subject and / or the unique shape of the head 10 of the subject. In some embodiments, the nasal support member 209 comprises a portion of the eyeglasses frame 207 or is otherwise integrally formed with the eyeglasses from 207. The one or more ear support members 211 may be shaped to extend over and / or bend or otherwise curve at least partially around one or more ears of the subject. In many embodiments, the one or more ear support members 211 are adjustable to allow repositioning of the eyeglasses frame 207 in a particular position on the head 10 of the subject depending on the selected target region in the brain of the subject and / or the unique shaped of the head 10 of the subject. For example, the one or more ear support members 211 may be configured to bend and then retain the shape to which the one or more ear support members 211 are bent.

[0048] The head support assembly 203 may further comprise a strap 206 secured or securable to the eyeglasses frame 207. The strap 206 may be adjustable and configured to selectively tighten or loosen the head support assembly 203 around the head 10 of the subject effective to support the wearable ultrasound device 200 in a selected position on the head 10 of the subject. In many embodiments, the strap 206 is detachably or fixedly secured to the one or more ear support members 211 of the eyeglasses frame 207. In some embodiments, the strap 206 may be detachably secured to the first member 205 or the transducers 202a, 202b.

[0049] Similar to the ultrasound device 100, an ultrasound system of this disclosure comprising the ultrasound device 200 coupled to the controller 201 may be configured to treat a variety of conditions or disorders in the brain. The transducers 202a, 202b may be positioned or selectively positionable to treat the variety of conditions or disorders in the brain For example, an ultrasound system including the ultrasound device 200 and the controller 201 may be configured to treat a condition of the brain including at least one of cognitive decline or Alzheimer’s disease, and the target region 20a may include one or more of a region of the brain associated with memory functions, a hippocampus of the brain, an entorhinal cortex of the brain, an amygdala of the brain, or a nucleus basalis of Meynert of the brain. In some embodiments, an ultrasound system including the ultrasound device 200 and the controller 201 may be configured to treat a condition of the brain including depression, and the target region 20a may include one or more of a cingulate cortex of the brain or a subcallosal cingulate cortex of the brain. In some embodiments, an114932-2944-1879' 1Docket No. P329919 WO.01 ultrasound system including the ultrasound device 200 and the controller 201 may be configured to treat a condition of the brain including chronic pain, and the target region 20a may include one or more of an anterior cingulate cortex of the brain, a medial cingulate cortex of the brain, a subcallosal cingulate cortex, a ventral posterolateral nucleus, or a ventral posteromedial nucleus. In some embodiments, an ultrasound system including the ultrasound device 200 and the controller 201 may be configured to treat a condition of the brain including addiction, and the target region 20a may include one or more of a nucleus accumbens of the brain, a subcallosal cingulate cortex of the brain, or an anterior cingulate cortex of the brain. In some embodiments, an ultrasound system including the ultrasound device 200 and the controller 201 may be configured to treat a condition of the brain including food cravings, and the target region 20a may include one or more of a nucleus accumbens of the brain or a nucleus accumbens shell of the brain. In some embodiments, an ultrasound system including the ultrasound device 200 and the controller 201 may be configured to treat a condition of the brain including anxiety, and the target region 20a may include one or more of an amygdala of the brain or a stria terminalis of the brain In some embodiments, an ultrasound system including the ultrasound device 200 and the controller 201 may be configured to treat a condition of the brain including post-traumatic brain disorder, and the target region 20a may include one or more of an amygdala of the brain or a bed nucleus of a stria terminalis of the brain.

[0050] Turning ahead in the drawings, FIG. 3A is a side view of a wearable ultrasound device 300 being worn by a subject and FIG. 3B is an isometric top rear view of the wearable ultrasound device 300 being worn by the subject, according to embodiments. The ultrasound device 300 is configured to be use in systems and methods that allow for reproducible positioning of the ultrasound device 300 with respect to the head 10. For example, the ultrasound device 300 may include a head support assembly 303 comprising a first member 305 shaped and dimensioned to fit around the head 10 of the subject The head support assembly 303 allows the ultrasound device 300 to be fitted on the head 10 of the subject while providing reproducible positioning of the ultrasound device 300 (e.g., the transducers 302a, 302b) on the head 10 of subject(s) across multiple treatment sessions and / or multiple subjects. The ultrasound device 300, using the head support assembly 303, positions the ultrasonic transducers 302a, 302b ultrasonic transducers to aim the ultrasonic waves 115 (shown in FIG. 1 ) into the desired brain target region 20a (shown in FIG. 1 ) for each specific indication (e.g., brain condition or disorder).

[0051] Unless otherwise noted or specified, the ultrasound system 300 may include any aspect of the ultrasound systems 100, 200 described above. Accordingly, like features are designated with like reference numerals with the leading digits incremented to “3 ” For example, the ultrasound system 300 may include a controller 301 , a head support assembly 303, one or more transducers 302a, 302b secured to the head support assembly 303 and configured to emit ultrasonic waves, and a coupling medium 304 that may, in some respects, resemble the controller 101 , 202, the head support 103, 203, the transducer 102, 202a-b secured to the head support 103, 203 and configured to emit the ultrasonic waves 115, and the coupling medium 104, 204 of the ultrasound system 100, 200.124932-2944-1879' 1Docket No. P329919 WO.01

[0052] As provided above, the first member 305 of the head support assembly 303 may be shaped and dimensioned to fit around the head 10 of the subject. More specifically, the first member 305 of the head support assembly 303 may comprise a front region 322 positioned to extend across the forehead of the subject, a rear region 322 positioned generally opposite to the front region 321 , and two side regions 323a, 323b extending at least partially between the front region 321 and the rear region 322.

[0053] The two transducers 302a, 302b may be secured to a different one of the two side regions 323a, 323b In other words, a first transducer 302a is secured or securable to a first side region 323a of the first member 303 and a second transducer 302a is secured or securable to a second side region 323b of the first member 303, according to embodiments herein. The two transducers 302a, 302b may be selectively movable and / or repositionable on the two side regions 323a, 323b of the first member 303. For example, the two transducers 302a, 302b may include or otherwise be secured to a transducer body 344a, 344b, respectively, and the side regions 323a, 323b may each include an elongated slot 345a, 345b. The head support assembly 303 also may include fasteners 343a, 343b selectively secured or securable to a respective transducer body 344a, 344b. For example, the fastener 343a, 343b may be threadedly fastened or fastenable to the transducer body 344a, 344b. At least one of the transducer body 344a, 344b or the fastener 343a, 343b may include an extension member (not visible) secured thereto or extending therefrom that is movably positioned or positionable in the elongated slot 345a, 345b. Each transducer 302a, 302b may be moved to adjust to the head 10 of the subject and / or the selected target region in the brain by loosing the fastener 343a, 343b, sliding the extension member within the slot 345a, 345b to move the transducer 302a, 302b to a selected position, and then tightening the fastener 343a, 343b to the transducer body 344a, 344b within the side region 323a, 323b therebetween. When the fastener 343a, 343b is tightened sufficiently, the transducer 302a, 302b becomes locked in a selected position on the head 10 to allow the transducer 302a, 302b to target the selected target region of the brain.

[0054] In some embodiments, the head support assembly 303 a front projection 331 extending inwardly from the front region 321 of the first member 305 and positioned to interface the forehead of the subject. The front projection 331 may include a pad to cushion against the head 10 of the subject. In some embodiments, the front projection 331 is adjustable and configured increase or decrease a distance between the front projection 331 and the rear region 322 effective to tighten or loosen the first member 305 on the head 10 of the subject and support the wearable ultrasound device 300 in a selected position on the head 10 of the subject. Said another way, the front projection 331 may be adjustable to increase or decrease a distance between the forehead of the subject and the front region 321 of the first member 305. The head support assembly 303 also may include a front fastener 341 selectively secured or securable to the front projection 331. Adjustment (e.g. , rotation) of the front fastener 341 moves the front projection 331 inward towards an axis of the first member 303 or outward away from the axis of the first member 303 to adjust an inner diameter or circumference of the first member 303134932-2944-1879' 1Docket No. P329919 WO.01

[0055] In some embodiments, the head support assembly 303 a rear projection 332 extending inwardly from the front region 322 of the first member 305 and positioned to interface the rear of the head 10 of the subject The rear projection 332 may include a pad to cushion against the head 10 of the subject. In some embodiments, the rear projection 332 is adjustable and configured increase or decrease a distance between the rear projection 332 and the front region 321 effective to tighten or loosen the first member 305 on the head 10 of the subject and support the wearable ultrasound device 300 in a selected position on the head 10 of the subject. Said another way, the rear projection 332 may be adjustable to increase or decrease a distance between the forehead of the subject and the rear region 322 of the first member 305. The head support assembly 303 also may include a rear fastener 342 selectively secured or securable to the rear projection 332 Adjustment (e.g., rotation) of the rear fastener 342 moves the rear projection 332 inward towards an axis of the first member 303 or outward away from the axis of the first member 303 to adjust an inner diameter or circumference of the first member 303.

[0056] In many embodiments, the head support assembly 303 includes a nasal support member 309 extending from at least one of the front projection 331 or the front region 321 of the first member 305. The nasal support member 309 is configured to rest on the nose 12 of the subject effective to support the wearable ultrasound device 300 in a selected position on the head 10 of the subject. The nasal support member 309 may be Y- or V-shaped and configured to rest on the nose 12 of the subject.

[0057] In many embodiments, the head support assembly 303 comprises one or more ear support members 311 configured to rest on one or more ears 14 of the subject effective to support the wearable ultrasound device 300 in a selected position on the head 10 of the subject. In some embodiments, the one or more ear support members 311 extend inward from the rear region 322 of the first member 305

[0058] Similar to the ultrasound device 100, 200 an ultrasound system of this disclosure comprising the ultrasound device 300 coupled to the controller 301 may be configured to treat a variety of conditions or disorders in the brain. The transducers 302a, 302b may be positioned or selectively positionable to treat the variety of conditions or disorders in the brain. For example, an ultrasound system including the ultrasound device 300 and the controller 301 may be configured to treat a condition of the brain including at least one of cognitive decline or Alzheimer’s disease, and the target region 20a may include one or more of a region of the brain associated with memory functions, a hippocampus of the brain, an entorhinal cortex of the brain, an amygdala of the brain, or a nucleus basalis of Meynert of the brain. In some embodiments, an ultrasound system including the ultrasound device 300 and the controller 301 may be configured to treat a condition of the brain including depression, and the target region 20a may include one or more of a cingulate cortex of the brain or a subcallosal cingulate cortex of the brain. In some embodiments, an ultrasound system including the ultrasound device 300 and the controller 301 may be configured to treat a condition of the brain including chronic pain, and the target region 20a may include one or more of an anterior cingulate cortex of the brain, a medial cingulate cortex of the brain, a subcallosal cingulate cortex, a ventral posterolateral nucleus, or a ventral posteromedial nucleus.144932-2944-1879' 1Docket No. P329919 WO.01In some embodiments, an ultrasound system including the ultrasound device 300 and the controller 301 may be configured to treat a condition of the brain including addiction, and the target region 20a may include one or more of a nucleus accumbens of the brain, a subcallosal cingulate cortex of the brain, or an anterior cingulate cortex of the brain. In some embodiments, an ultrasound system including the ultrasound device 300 and the controller 301 may be configured to treat a condition of the brain including food cravings, and the target region 20a may include one or more of a nucleus accumbens of the brain or a nucleus accumbens shell of the brain. In some embodiments, an ultrasound system including the ultrasound device 300 and the controller 301 may be configured to treat a condition of the brain including anxiety, and the target region 20a may include one or more of an amygdala of the brain or a stria terminalis of the brain In some embodiments, an ultrasound system including the ultrasound device 300 and the controller 301 may be configured to treat a condition of the brain including post-traumatic brain disorder, and the target region 20a may include one or more of an amygdala of the brain or a bed nucleus of a stria terminalis of the brain.

[0059] T urning ahead in the drawings, FIG. 4 is a flow diagram of a method 400 of stimulating a target region of in a brain of a subject, according to embodiments disclosed herein. The method 400 may utilize any of the ultrasound systems 100, 200, 300 disclosed herein In many embodiments, the method 400 comprises providing 405 a wearable ultrasound device comprising two transducers and a head support assembly having the two transducers secured thereto. The method 400 also may comprise positioning 410 the two transducers of the wearable ultrasound device on a head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject The method 400 also may comprise supporting 415 the two transducers in a selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device The method 400 also may comprise, with a controller coupled to the two transducers, activating 420 the two transducers to generate ultrasonic waves effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject

[0060] In particular embodiments, the ultrasound device 300 may be used in the method 400. Accordingly, positioning 410 the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject may comprise positioning the first member of the head support assembly around the head of the subject with a front region of the first member extending across the forehead of the subject, a rear region of the first member positioned generally opposite to the front region, and two side regions of the first member extending between the front region and the rear region The two transducers being secured to a different one the two side regions with the head of the subject between the two transducers

[0061] In these embodiments of the method 400 using the ultrasound device 300, as well as other embodiments, the method 400 may further comprises at least one (e g , both) of (1 ) interfacing a front projection of the head support assembly with the forehead of the subject, the154932-2944-1879' 1Docket No. P329919 WO.01 front projection extending inwardly from the front region of the first member or (2) interfacing a rear projection of the head support assembly with a rear of the head of the subject, the rear projection extending inwardly from the rear region of the first member. The method 400 may further comprise adjusting at least one of the front projection or the rear projection to increase or decrease a distance between the front projection and the rear projection effective to tighten or loosen the first member on the head of the subject and support the wearable ultrasound device in the selected position on the head of the subject.

[0062] In these embodiments of the method 400 using the ultrasound device 300, as well as other embodiments, supporting 415 the two transducers in the selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device may comprise at least resting a nasal support member on the nose of the subject, the nasal support member extending from at least one the front projection or the front region of the first member.

[0063] In these embodiments of the method 400 using the ultrasound device 300, as well as other embodiments, supporting the two transducers in the selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device may comprise at least resting one or more ear support members on one or more ears of the subject. The one or more ear support members extend inward from the rear region of the first member. In these embodiments of the method 400 using the ultrasound device 300, as well as other embodiments, the method may further comprise moving the two transducers on the two side regions of the first member to a selected transducer position for the subject.

[0064] In particular embodiments, the ultrasound device 200 may be used in the method 400. In these embodiments of the method 400 using the ultrasound device 200, as well as other embodiments, positioning 410 the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject may comprise positioning the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers, the first member of the head support assembly extending across a forehead of the subject, a nasal support member of an eyeglasses frame of the head support assembly resting on the nose of the subject, and one or more ear support members of the head support assembly resting on one or more ears of the subject, the eyeglasses frame being secured to the first member of the head support assembly. In these embodiments of the method 400 using the ultrasound device 200, as well as other embodiments, the method 400 may further comprise adjusting a strap of the head support assembly to tighten or loosen the head support assembly around the head of the subject.

[0065] In many embodiments of the method 400, activating 420 the two transducers to generate ultrasonic waves effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject comprises activating the two transducers to generate ultrasonic waves at a frequency of about 200 kHz to about 400 kHz effective to stimulate the target164932-2944-1879' 1Docket No. P329919 WO.01 region of the brain of the subject without ablating the target region of the brain of the subject. The ultrasonic waves generated by the two transducers in the method 400 may have a focal width that is at least two times larger than the target region in the brain of the subject.

[0066] In some embodiments of the method 400, the target region may comprise a region of the brain that is associated with at least one of cognitive decline or Alzheimer’s disease In these and other embodiments of the method 400, the target region may include one or more of a region of the brain associated with memory functions, a hippocampus of the brain, an entorhinal cortex of the brain, an amygdala of the brain, or a nucleus basalis of Meynert of the brain.

[0067] In some embodiments of the method 400, the target region may comprise a region of the brain associated with depression. In these and other embodiments of the method 400, the target region may include one or more of a cingulate cortex of the brain or a subcallosal cingulate cortex of the brain

[0068] In some embodiments of the method 400, the target region may comprise a region of the brain associated with chronic pain. In these and other embodiments of the method 400, the target region may include one or more of an anterior cingulate cortex of the brain, a medial cingulate cortex of the brain, a subcallosal cingulate cortex, a ventral posterolateral nucleus, or a ventral posteromedial nucleus.

[0069] In some embodiments of the method 400, the target region may comprise a region of the brain associated with addiction In these and other embodiments of the method 400, the target region may include one or more of a nucleus accumbens of the brain, a subcallosal cingulate cortex of the brain, or an anterior cingulate cortex of the brain.

[0070] In some embodiments of the method 400, the target region may comprise a region of the brain associated with food craving. In these and other embodiments of the method 400, the target region may include one or more of a nucleus accumbens of the brain or a nucleus accumbens shell of the brain.

[0071] In some embodiments of the method 400, the target region may comprise a region of the brain associated with anxiety In these and other embodiments of the method 400, the target region may include one or more of an amygdala of the brain or a stria terminalis of the brain.

[0072] In some embodiments of the method 400, the target region may comprise a region of the brain associated with post-traumatic brain disorder. In these and other embodiments of the method 400, the target region may include one or more of an amygdala of the brain or a bed nucleus of a stria terminalis of the brain.

[0073] 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.

[0074] Similar to the method 400, also disclosed herein is a method of treating a condition of a brain of a subject. This method may comprise providing wearable ultrasound device comprising two transducers and a head support assembly having the two transducers secured thereto This method also may comprise positioning the two transducers of the wearable ultrasound device on174932-2944-1879' 1Docket No. P329919 WO.01 a head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject. This method also may comprise supporting the two transducers in a selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device. This method also may comprise, with a controller coupled to the two transducers, activating the two transducers to generate ultrasonic waves effective to stimulate a target region of the brain of the subject without ablating the target region of the brain of the subject, the target region being associated with the condition of the brain

[0075] This method of treating a condition of a brain of a subject may use the ultrasound devices 200, 300 and controllers 201 , 301 as described above in relation to the method 400 In some embodiments of this method of treating a condition of a brain of a subject, the condition of the brain may include at least one of cognitive decline or Alzheimer’s disease and the target region may include one or more of a region of the brain associated with memory functions, a hippocampus of the brain, an entorhinal cortex of the brain, an amygdala of the brain, or a nucleus basalis of Meynert of the brain.

[0076] In some embodiments of this method of treating a condition of a brain of a subject, the condition of the brain may include depression and the target region may one or more of a cingulate cortex of the brain or a subcallosal cingulate cortex of the brain.

[0077] In some embodiments of this method of treating a condition of a brain of a subject, the condition of the brain may include chronic pain and the target region includes one or more of an anterior cingulate cortex of the brain, a medial cingulate cortex of the brain, a subcallosal cingulate cortex, a ventral posterolateral nucleus, or a ventral posteromedial nucleus.

[0078] In some embodiments of this method of treating a condition of a brain of a subject, the condition of the brain may include addiction and the target region may include one or more of a nucleus accumbens of the brain, a subcallosal cingulate cortex of the brain, or an anterior cingulate cortex of the brain

[0079] In some embodiments of this method of treating a condition of a brain of a subject, the condition of the brain may include food craving and the target region may include one or more of a nucleus accumbens of the brain or a nucleus accumbens shell of the brain.

[0080] In some embodiments of this method of treating a condition of a brain of a subject, the condition of the brain may include anxiety and the target region may include one or more of an amygdala of the brain or a stria terminalis of the brain.

[0081] In some embodiments of this method of treating a condition of a brain of a subject, the condition of the brain may include post-traumatic brain disorder and the target region may include one or more of an amygdala of the brain or a bed nucleus of a stria terminalis of the brain.

[0082] 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. For184932-2944-1879' 1Docket No. P329919 WO.01 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.

[0083] 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.

[0084] 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.

[0085] 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.194932-2944-1879' 1

Claims

Docket No. P329919 WO.

011. A wearable ultrasound device, comprising: two transducers configured to operably couple to a controller and configured to selectively generate ultrasonic waves; and a head support assembly having the two transducers secured thereto and configured to support the two transducers on a head of the subject with the head of the subject positioned between the two transducers, the head support assembly including at least a first member positioned to extend across a forehead of a subject and one or more members configured to rest on at least one of a nose or an ear of the subject, wherein the head support assembly is configured position the two transducers on the head of the subject to deliver ultrasonic waves at a target region in a brain of the subject without ablating the target region.

2. The wearable ultrasound device of claim 1 , wherein the first member of the head support assembly is shaped and dimensioned to fit around the head of the subject, the first member of the head support assembly comprising a front region positioned to extend across the forehead of the subject, a rear region positioned generally opposite to the front region, and two side regions extending at least partially between the front region and the rear region, the two transducers being secured to a different one of the two side regions.

3. The wearable ultrasound device of claim 2, wherein the head support assembly comprises at least one of: a front projection extending inwardly from the front region of the first member and positioned to interface the forehead of the subject; or a rear projection extending inwardly from the rear region of the first member and positioned to interface a rear of the head of the subject.

4. The wearable ultrasound device of claim 3, wherein the head support assembly comprises both the front projection and the rear projection, and wherein at least one of the front projection or the rear projection is adjustable to increase or decrease a distance between the front projection and the rear projection effective to tighten or loosen the first member on the head of the subject and support the wearable ultrasound device in a selected position on the head of the subject5. The wearable ultrasound device of either claim 3 or claim 4, wherein the head support assembly comprises at least the front projection and the head support assembly includes a nasal support member extending from at least one of the front projection or the front region of the first member, the nasal support member configured to rest on the nose of the subject effective to support the wearable ultrasound device in a selected position on the head of the subject.

6. The wearable ultrasound device of any of claims 2-5, wherein the head support assembly comprises one or more ear support members configured to rest on one or more ears of the subject effective to support the wearable ultrasound device in a selected position on the head of the subject.204932-2944-1879' 1Docket No. P329919 WO.

017. The wearable ultrasound device of claim 6, wherein the one or more ear support members extend inward from the rear region of the first member.

8. The wearable ultrasound device of any of claims 2-7, wherein the two transducers are selectively movable on the two side regions of the first member.

9. The wearable ultrasound device of claim 1 , wherein the head support assembly further comprises an eyeglasses frame secured to the first member of the head support assembly, the eyeglasses frame comprising a nasal support member configured to rest on the nose of the subject and one or more ear support members configured to rest on one or more ears of the subject effective to support the wearable ultrasound device in a selected position on the head of the subject.

10. The wearable ultrasound device of claim 9, wherein the head support assembly further comprises a strap secured or securable to the eyeglasses frame, the strap being adjustable and configured to selectively tighten or loosen the head support assembly around the head of the subject effective to support the wearable ultrasound device in a selected position on the head of the subject.11 The wearable ultrasound device of either claim 9 or claim 10, wherein the head support assembly further comprises an arm secured to the first member and the eyeglasses frame effective to secure the eyeglasses frame to the first member.

12. The wearable ultrasound device of claim 11 , wherein at least one of the eyeglasses frame or the first member is adjustably secured to the arm.

13. The wearable ultrasound device of any of claims 1-12, wherein the two transducers are configured to selectively generate ultrasonic waves at a frequency of about 200 kHz to about 400 kHz effective to stimulate the target region in the brain of the subject without ablating the target region.

14. The wearable ultrasound device of claim 13, wherein the ultrasonic waves generated by the two transducers have a focal width that is at least two times larger than the target region in the brain of the subject.

15. The wearable ultrasound device of claim 14, further comprising the controller operably coupled to the two transducers.16 A method of stimulating a target region of a brain of a subject, the method comprising: providing a wearable ultrasound device comprising two transducers and a head support assembly having the two transducers secured thereto; positioning the two transducers of the wearable ultrasound device on a head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject; and supporting the two transducers in a selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device; and214932-2944-1879' 1Docket No. P329919 WO.01 with a controller coupled to the two transducers, activating the two transducers to generate ultrasonic waves effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject.

17. The method of claim 16, wherein positioning the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject comprises: positioning the first member of the head support assembly around the head of the subject with a front region of the first member extending across the forehead of the subject, a rear region of the first member positioned generally opposite to the front region, and two side regions of the first member extending at least partially between the front region and the rear region, the two transducers being secured to a different one of the two side regions with the head of the subject between the two transducers.

18. The wearable ultrasound device of claim 17, further comprising at least one of: interfacing a front projection of the head support assembly with the forehead of the subject, the front projection extending inwardly from the front region of the first member; or interfacing a rear projection of the head support assembly with a rear of the head of the subject, the rear projection extending inwardly from the rear region of the first member.

19. The method of claim 18, further comprising: wherein the method includes both interfacing the front projection of the head support assembly with the forehead of the subject and interfacing the rear projection of the head support assembly with the rear of the head of the subject; and adjusting at least one of the front projection or the rear projection to increase or decrease a distance between the front projection and the rear projection effective to tighten or loosen the first member on the head of the subject and support the wearable ultrasound device in the selected position on the head of the subject.

20. The method of either claim 18 or claim 19, wherein supporting the two transducers in the selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device comprises at least resting a nasal support member on the nose of the subject, the nasal support member extending from at least one of the front projection or the front region of the first member.21 . The method of any of claims 17-20, wherein supporting the two transducers in the selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device comprises at least resting one or more ear support members on one or more ears of the subject.22 The method of claim 21, wherein the one or more ear support members extend inward from the rear region of the first member.

23. The method of any of claims 17-22, further comprising moving the two transducers on the two side regions of the first member to a selected transducer position for the subject.224932-2944-1879' 1Docket No. P329919 WO.0124. The method of claim 16, wherein positioning the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject comprises: positioning the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers, the first member of the head support assembly extending across a forehead of the subject, a nasal support member of an eyeglasses frame of the head support assembly resting on the nose of the subject, and one or more ear support members of the head support assembly resting on one or more ears of the subject, the eyeglasses frame being secured to the first member of the head support assembly.

25. The method of claim 24, further comprising adjusting a strap of the head support assembly to tighten or loosen the head support assembly around the head of the subject.

26. The method of any of claims 16-25, wherein activating the two transducers to generate ultrasonic waves effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject comprises activating the two transducers to generate ultrasonic waves at a frequency of about 200 kHz to about 400 kHz effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject27. The method of claim 26, wherein the ultrasonic waves generated by the two transducers have a focal width that is at least two times larger than the target region in the brain of the subject.

28. The method of any of claims 16-27, wherein the target region comprises a region of the brain associated with at least one of cognitive decline or Alzheimer's disease, the target region including one or more of a region of the brain associated with memory functions, a hippocampus of the brain, an entorhinal cortex of the brain, an amygdala of the brain, or a nucleus basalis of Meynert of the brain.

29. The method of any of claims 16-27, wherein the target region comprises a region of the brain associated with depression, the target region including one or more of a cingulate cortex of the brain or a subcallosal cingulate cortex of the brain30 The method of any of claim 16-27, wherein the target region comprises a region of the brain associated with chronic pain, the target region including one or more of an anterior cingulate cortex of the brain, a medial cingulate cortex of the brain, a subcallosal cingulate cortex, a ventral posterolateral nucleus, or a ventral posteromedial nucleus.31 . The method of any of claims 16-27, wherein the target region comprises a region of the brain associated with addiction, the target region including one or more of a nucleus accumbens of the brain, a subcallosal cingulate cortex of the brain, or an anterior cingulate cortex of the brain32. The method of any of claims 16-27, wherein the target region comprises a region of the brain associated with food craving, the target region including one or more of a nucleus accumbens of the brain or a nucleus accumbens shell of the brain.234932-2944-1879' 1Docket No. P329919 WO.0133. The method of any of claims 16-27, wherein the target region comprises a region of the brain associated with anxiety, the target region including one or more of an amygdala of the brain or a stria terminals of the brain.

34. The method of any of claims 16-27, wherein the target region comprises a region of the brain associated with post-traumatic brain disorder, the target region including one or more of an amygdala of the brain or a bed nucleus of a stria terminalis of the brain.

35. A method of treating a condition of a brain of a subject, the method comprising: providing a wearable ultrasound device comprising two transducers and a head support assembly having the two transducers secured thereto; positioning the two transducers of the wearable ultrasound device on a head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject; and supporting the two transducers in a selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device; and with a controller coupled to the two transducers, activating the two transducers to generate ultrasonic waves effective to stimulate a target region of the brain of the subject without ablating the target region of the brain of the subject, the target region being associated with the condition of the brain36. The method of claim 35, wherein positioning the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject comprises: positioning the first member of the head support assembly around the head of the subject with a front region of the first member extending across the forehead of the subject, a rear region of the first member positioned generally opposite to the front region, and two side regions of the first member extending at least partially between the front region and the rear region, the two transducers being secured to a different one of the two side regions with the head of the subject between the two transducers.37 The wearable ultrasound device of claim 36, further comprising at least one of: interfacing a front projection of the head support assembly with the forehead of the subject, the front projection extending inwardly from the front region of the first member; or interfacing a rear projection of the head support assembly with a rear of the head of the subject, the rear projection extending inwardly from the rear region of the first member.

38. The method of claim 37, further comprising: wherein the method includes both interfacing the front projection of the head support assembly with the forehead of the subject and interfacing the rear projection of the head support assembly with the rear of the head of the subject; and adjusting at least one of the front projection or the rear projection to increase or decrease a distance between the front projection and the rear projection effective to tighten or loosen the244932-2944-1879' 1Docket No. P329919 WO.01 first member on the head of the subject and support the wearable ultrasound device in the selected position on the head of the subject.

39. The method of either claim 37 or claim 38, wherein supporting the two transducers in the selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device comprises at least resting a nasal support member on the nose of the subject, the nasal support member extending from at least one of the front projection or the front region of the first member.40 The method of any of claims 36-39, wherein supporting the two transducers in the selected position on the head of the subject by positioning one or more members of the head support assembly on at least one of a nose or an ear of the subject to support the wearable device comprises at least resting one or more ear support members on one or more ears of the subject.

41. The method of claim 40, wherein the one or more ear support members extend inward from the rear region of the first member.

42. The method of any of claims 36-41 , further comprising moving the two transducers on the two side regions of the first member to a selected transducer position for the subject43. The method of claim 35, wherein positioning the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers and a first member of the head support assembly extending across a forehead of the subject comprises: positioning the two transducers of the wearable ultrasound device on the head of the subject with the head positioned between the two transducers, the first member of the head support assembly extending across a forehead of the subject, a nasal support member of an eyeglasses frame of the head support assembly resting on the nose of the subject, and one or more ear support members of the head support assembly resting on one or more ears of the subject, the eyeglasses frame being secured to the first member of the head support assembly.

44. The method of claim 43, further comprising adjusting a strap of the head support assembly to tighten or loosen the head support assembly around the head of the subject.

45. The method of any of claims 35-44, wherein activating the two transducers to generate ultrasonic waves effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject comprises activating the two transducers to generate ultrasonic waves at a frequency of about 200 kHz to about 400 kHz effective to stimulate the target region of the brain of the subject without ablating the target region of the brain of the subject46. The method of claim 45, wherein the ultrasonic waves generated by the two transducers have a focal width that is at least two times larger than the target region in the brain of the subject47. The method of any of claims 35-46, wherein the condition of the brain includes at least one of cognitive decline or Alzheimer’s disease and the target region includes one or more of a region of the brain associated with memory functions, a hippocampus of the brain, an254932-2944-1879' 1Docket No. P329919 WO.01 entorhinal cortex of the brain, an amygdala of the brain, or a nucleus basalis of Meynert of the brain.

48. The method of any of claims 35-46, wherein the condition of the brain includes depression and the target region includes one or more of a cingulate cortex of the brain or a subcallosal cingulate cortex of the brain.

49. The method of any of claim 35-46, wherein the condition of the brain includes chronic pain and the target region includes one or more of an anterior cingulate cortex of the brain, a medial cingulate cortex of the brain, a subcallosal cingulate cortex, a ventral posterolateral nucleus, or a ventral posteromedial nucleus50. The method of any of claims 35-46, wherein the condition of the brain includes addiction and the target region includes one or more of a nucleus accumbens of the brain, a subcallosal cingulate cortex of the brain, or an anterior cingulate cortex of the brain.

51. The method of any of claims 35-46, wherein the condition of the brain includes food craving and the target region includes one or more of a nucleus accumbens of the brain or a nucleus accumbens shell of the brain.52 The method of any of claims 35-46, wherein the condition of the brain includes anxiety and the target region includes one or more of an amygdala of the brain or a stria terminals of the brain53. The method of any of claims 35-46, wherein the condition of the brain includes post-traumatic brain disorder and the target region includes one or more of an amygdala of the brain or a bed nucleus of a stria terminalis of the brain.264932-2944-1879' 1

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