Patent Publication Number: US-2016243381-A1

Title: Systems and techniques for ultrasound neuroprotection

Description:
TECHNICAL FIELD 
     The disclosure relates to medical therapies and, more particularly, ultrasound delivery. 
     BACKGROUND 
     Neurodegenerative diseases can occur in older adults and may result in cognitive impairment of brain function, motor dysfunction, or even death. Such diseases may include Parkinson&#39;s disease, Alzheimer&#39;s disease, amyotrophic lateral sclerosis (ALS), Huntington&#39;s disease, and others. A clinician may treat a patient with a neurodegenerative disease using one or more therapies. Oral medication may be prescribed for some patients. Patients may also or alternatively be treated using drug delivery therapy and/or electrical stimulation therapy. Electrical stimulation therapy may include deep brain stimulation (DBS), although other types of electrical stimulation therapy may be employed for some patients. Typically, patients are not treated with DBS until after other, less invasive, treatments are not efficacious. 
     SUMMARY 
     In general, the disclosure is directed to techniques and/or systems for reducing degeneration of neurons of a brain of a patient. For example, at early stages of a neurodegenerative disease, a system may be configured to deliver ultrasound energy to a targeted region of the brain of the patient to reduce or prevent the degeneration of neurons in a selected region of the brain that may be similar or different from the targeted region. The system may include one or more ultrasound transducers placed on an exterior surface of the patient&#39;s head and configured to deliver the ultrasound energy focused to the targeted region. The ultrasound energy may be defined by a set of ultrasound parameters selected to affect the selected region of the brain corresponding to the neurodegenerative disease. The ultrasound energy may stimulate the neurons within the selected region of the brain associated with the targeted region of the brain receiving the ultrasound energy. The targeted region may be completely separate or distinct from or at least partially include the selected region. This stimulation resulting from the delivery of ultrasound energy can provide neuroprotective effects that may reduce, halt, or even reverse the degeneration of neurons in the selected region of the brain that may otherwise occur from the neurogenerative disease. 
     In one aspect, the disclosure is directed to a method for reducing or preventing neural degeneration within a brain of a patient, wherein the method includes delivering, via one or more ultrasound transducers, ultrasound energy focused to a targeted region of the brain of the patient according to ultrasound parameters, wherein the ultrasound parameters are selected to generate ultrasound energy that reduces or prevents neural degeneration within at least a portion of the brain. 
     In another aspect, the disclosure is directed to a system for reducing or preventing neural degeneration within a brain of a patient, wherein the system includes an ultrasound module configured to deliver, via one or more ultrasound transducers, ultrasound energy focused to a targeted region of the brain of the patient and a processor configured to control the ultrasound module to deliver the ultrasound energy to the targeted region according to ultrasound parameters, wherein the ultrasound parameters are selected to generate the ultrasound energy that reduces or prevents neural degeneration within at least a portion of the brain. 
     In a further aspect, the disclosure is directed to a system for reducing or preventing neural degeneration within a brain of a patient, wherein the system includes means for delivering ultrasound energy focused to a targeted region of the brain of the patient and means for controlling the means for delivering ultrasound energy to deliver the ultrasound energy to the targeted region according to ultrasound parameters, wherein the ultrasound parameters are selected to generate the ultrasound energy that reduces or prevents neural degeneration within at least a portion of the brain. 
     The details of one or more example are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  is a conceptual diagram illustrating an example system that delivers ultrasound energy to a targeted region of a brain of a patient to reduce neural degeneration within a selected region of the brain, according to one or more aspects disclosed herein. 
         FIG. 2  is a conceptual diagram illustrating an example wearable device that includes an array of ultrasound transducers that deliver ultrasound energy to a targeted region of the brain. 
         FIG. 3  is a conceptual diagram illustrating example ultrasound transducers that can be used to focus ultrasound energy to a targeted region of a brain. 
         FIG. 4  is a schematic diagram of example regions and circuits within a brain of a patient. 
         FIG. 5  is a block diagram illustrating an example configuration of a controller device which may be utilized in the system of  FIGS. 1 and 2 . 
         FIG. 6  is a flow diagram that illustrates an example process for determining a set of ultrasound parameters that at least partially define ultrasound energy deliverable to a targeted region of a brain of a patient. 
         FIG. 7  is a flow diagram that illustrates an example process for delivering ultrasound energy focused to a targeted region of a brain of a patient to reduce neural degeneration within a selected region of the brain. 
     
    
    
     DETAILED DESCRIPTION 
     The disclosure is directed to techniques and systems for reducing degeneration of neurons within of a brain of a patient. Various neurodegenerative diseases (e.g., Parkinson&#39;s disease, Alzheimer&#39;s disease, amyotrophic lateral sclerosis (ALS), Huntington&#39;s disease, dystonia, tremor, dyskinesia, bradykinesia, dementia, or chronic pain) occur in the adult population and can include symptoms such as motor dysfunction and/or cognitive impairment. The cause of these symptoms typically includes the degeneration of neural networks within one or more regions of the brain over time. Degeneration of neurons may be caused by dopamine depleting neurotoxins, chemicals, viruses, tumors, and/or one or more physiological events. Neurons may degenerate over weeks, months, or years resulting in increased, or more frequent, symptoms. 
     Deep brain electrical stimulation (DBS) directed to one or more regions of the brain may be an effective treatment of motor dysfunction and/or cognitive impairment resulting from a neurogenerative disease. For example, DBS may alleviate tremors, bradykinesia, and speech problems experienced by a patient diagnosed with Parkinson&#39;s disease. In addition, DBS may even slow the progression of a neurodegenerative disease. The electrical stimulation from DBS may protect the nigrostratial system, for example, from dopamine depleting neurotoxins that would otherwise contribute to the degeneration of the neurons. However, DBS may not be an appropriate preventative therapy for patients recently diagnosed with, or at risk for, neurodegenerative diseases. Since DBS is an invasive therapy that requires electrodes implanted within the brain of the patient, DBS is typically reserved for patients in whom the neurogenerative disease has progressed to a stage at which less invasive therapies (e.g., oral medications or other drug therapies) no longer alleviate symptoms. At this later stage in the progression of the disease, when significant neuron loss has already occurred—sometimes over five years from when the first symptoms were identified—the benefits from protecting remaining neurons may be minimal. 
     As described herein, various techniques and systems may be used to non-invasively reduce or prevent degeneration of neurons in the brain of the patient. For example, a system may include one or more ultrasound transducers placed on an exterior surface of the patient&#39;s head (e.g., in contact with the skin of the head) and configured to deliver the ultrasound energy focused to a targeted region of the brain. The ultrasound transducers may take the form of an array of ultrasound transducers positioned on the head of the patient in a configuration selected to focus the ultrasound energy generated by the transducers to the targeted region. The ultrasound transducers may be individually attached to the head of the patient, or in some cases, mounted within a wearable device (e.g., a cap or helmet) that is positioned on the head of the patient. In other examples, one or more ultrasound transducers that deliver ultrasound energy to the patient may be surgically attached to the patients skull (e.g., beneath the surface of the skin) to focus the ultrasound energy from the ultrasound transducers to the targeted region of the brain of the patient. Ultrasound transducers may be positioned to stereotactically deliver (e.g., precise delivery to a specific locus in a three-dimensional space) the ultrasound energy to a targeted region of the brain. One or more controller devices may control the ultrasound transducers. 
     The ultrasound energy may be defined by a set of ultrasound parameters selected to affect a selected region of the brain corresponding to the neurodegenerative disease, e.g., by stimulating neurons in the selected region. For example, the selected region may be a substantia nigra (SN) for a patient diagnosed with Parkinson&#39;s disease or at risk for Parkinson&#39;s disease. The ultrasound energy may stimulate the neurons within the selected region of the brain. In some examples, the targeted region of the brain to which the ultrasound energy is focused may include all, or at least a portion of, the selected region that includes the neurons at risk for degeneration. In other examples, the selected region may be separate or distinct from the targeted region. The neurons within the targeted region may be in a circuit with neurons of the selected region and thus affect the neurons of the selected region. In this manner, the selected region may be associated with the targeted region of the brain receiving the ultrasound energy. 
     The stimulation of neurons resulting from the delivery of ultrasound energy can provide neuroprotective effects that may prevent, reduce, or even halt, the degeneration of the neurons in the selected region of the brain that would have otherwise occurred from the neurogenerative disease. For example, the neuroprotective ultrasound energy may elicit an increase in the metabolism (e.g., increased oxygen levels) of affected brain circuits to protect selected regions of the brain from atrophy or degeneration. The ultrasound neuromodulation described herein may be considered non-invasive. In this manner, a clinician may prescribe ultrasound neuromodulation for a patient at the very earliest stages of a newly diagnosed disease (e.g., concurrent with or before medication treatment) or even responsive to the patient meeting one or more risk factors for a potential neurogenerative disease. Early application of ultrasound neuromodulation of one or more regions of the brain may prevent, reduce, halt, or even reverse the progression of one or more neurogenerative diseases and mitigate associated symptoms. Reversing the progression of a neurogenerative disease may include improving the functionality of neurons and/or neural networks within the patient and may reduce symptoms related to the neurogenerative disease. 
     Although the techniques primarily described in this disclosure are for reducing degeneration of neurons in one or more regions of the brain of a patient, ultrasound energy may be applied to nerves or any nervous system tissue at other locations of the body to protect such nerves or tissue from degeneration or otherwise slow the progression of a neurogenerative disease. For example, the devices, systems, and techniques described in this disclosure alternatively or additionally may be directed to other fiber tracks of the central nervous system (e.g., the spinal cord), branches therefrom, or peripheral nerves. These nerves may include sensory nerves, motor nerves, or spinal nerves. 
       FIG. 1  is a conceptual diagram illustrating an example system  10  that delivers ultrasound energy to a targeted region of brain  16  of patient  12  to reduce neuron degeneration within a selected region of brain  16 . As shown in  FIG. 1 , system  10  includes transducer substrate  22  in the form of a helmet or cap that may be adjustable for fitting externally along a patient&#39;s cranium  14 . Substrate  22  may carry one or more ultrasound transducers  24 A through  24 N (collectively “ultrasound transducer array  23 ”). Transducers  24 A through  24 N may be embedded in or coated with an acoustical coupling medium to minimize signal losses between the transducer surfaces and the exterior surface of the skin of patient  12 . Transducers  24 A through  24 N may or may not include an acoustic lens. An acoustic lens associated with a particular transducer in ultrasound transducer array  23  may be configured as an actively adjustable acoustic lens where the focal parameters may be controlled by controller device  28 . 
     Although transducers  24 A- 24 N are shown in a substantially straight line along cranium  14 , transducers  24 A- 24 N may be positioned at different circumferential positions around cranium  14  and/or additional ultrasound transducers may be positioned along one or more sides of cranium  14 . In this manner, not all of the ultrasound transducers of array  23  may be visible in the sagittal plane cross-section of  FIG. 1 . In addition, the spacing between one or more transducers  24 A- 24 N may be varied as necessary to focus ultrasound energy to appropriate targeted regions of brain  16 . In some examples, the structure that carries transducers  24 A- 24 N (e.g., helmet or cap) may allow for varying the spatial arrangement of the transducers. For instance, the special arrangement may be varied based on a particular patient&#39;s anatomy and/or based on the target region of brain  16  that is to be stimulated. 
     In the example of  FIG. 1 , transducer array  23  is coupled to controller device  28  via cable  26  for controlling ultrasound wave emission (e.g., delivery of ultrasound energy) by ultrasound transducer array  23 . In other examples, controller device  28  may be attached to or embedded within substrate  22  or other portion of the helmet or cap. In other words, controller  28  may control each of ultrasound transducers  24 A- 24 N to generate ultrasound energy according to a set of ultrasound parameters. In addition, transducer array  23  may also be coupled to a data collection module for acquiring signals from transducer array  23 . The acquired signals may be signals emanated from one or more regions of brain  16  or signals in response to transmitted waves from ultrasound transducer array  23 . Controller device  28  may be configured to control each of transducers  24 A- 24 N individually. Controller device  28  may select transducers  24 A- 24 N one at a time or in any combination for emitting ultrasound waves from ultrasound transducer array  23 . 
     Controller device  28  may be configured to selectively control which of transducers  24 A- 24 N are enabled for delivery of ultrasound energy (e.g., waveforms) and which transducers  24 A- 24 N are not enabled (i.e., turned off). Controller device  28  controls the transducers of array  23  to generate waveforms corresponding to a set of ultrasound parameters. The ultrasound parameters may include, but are not limited to, identification of active ultrasound transducers, waveform shape, waveform amplitude, waveform frequency, duty cycle, the waveform phase, the number of waveforms within each burst of waveforms, and the frequency of bursts of waveforms. The waveform phase may be defined with respect to another transducer waveform, for example, a waveform generated by an adjacent transducer within array  23 , a center transducer of array  23 , or end transducer  24 A or  24 N, or another common time or clock reference. 
     In one example, controller device  28  may be configured to control the waveform phase of each transducer  24 A- 24 N to select a therapy pathway for each of the individually emitting transducers  24 A or  24 N. For example, controller device  28  may control transducers  24 A or  24 N to emit ultrasound energy in the form of waveforms in a phase relationship that results in the waveforms being transmitted along pathways  30  (shown as solid lines in the example of  FIG. 1 ) from respective transducers of array  23  to focus the emitted ultrasound energy from all of the selected emitting transducers  24 A or  24 N at a first targeted region  18 . Controller device  28  may also adjust the phase relationship between transducers  24 A or  24 N to redirect the ultrasound waveforms along pathways  32  (shown as dotted lines in the example of  FIG. 1 ) to focus the ultrasound energy at a different, second targeted region  20 . 
     In this way, a transducer array  23  can be controlled to emit and focus ultrasound energy to reduce degeneration of neurons at one or more selected regions associated with one or more targeted regions (e.g., targeted regions  18  and  20 ). The volume and shape of targeted regions  18  and  20 , for example, may depend in part on the number of transducers and inter-transducer waveform phase relationships selected by controller device  28 . 
     In some examples, each of targeted regions  18  and  20  may include respective selected regions within which the ultrasound energy is intended to reduce degeneration of neurons. In other words, targeted regions  18  and  20  may include at least a portion of a respective selected region, all of a respective selected region, or even be the same as the respective selected regions. Alternatively, targeted regions  18  and  20  may be separate or distinct (e.g., non-overlapping) from the associated selected regions. Since the targeted regions  18  and  20  may affect respective selected regions via a neural circuit (e.g., neurons within a targeted region may be connected with neurons in a selected region), ultrasound energy may be focused to a targeted region (e.g., regions  18  and  20 ) in order to affect neurons within a different selected region of brain  16 . 
     When multiple targeted regions are to receive ultrasound energy, controller device  28  can be configured to step through a programmed (or predetermined) set of target regions or along one or more known brain circuits to deliver the protective ultrasound neuromodulation described herein. In some examples, such predetermined sets of regions may be used to receive signals from the respective regions indicative of a brain state status (e.g., resting or elevated brain state) and/or to identify the desired target or selected regions. Target regions may be selected one at a time in a sequential manner or selected two or more at time for simultaneous neuromodulation at more than one target region. A menu, or set, of target regions used by controller device  28  to select one or more transducers  24 A- 24 N may include regions selected one at a time or in combination, in any desired order. In addition, the target regions may be selected based on one or more selected regions for which the neurons may be at risk of degeneration. In other words, the target regions may be selected in order to affect one or more selected regions. 
     In some examples, controller device  28  may control array  23  to operate in a receiving mode for measuring reflections of ultrasound waves for use as feedback in focusing ultrasound energy on a target region and/or for measuring a functional response (e.g., a brain state) to neuromodulation. Controller device  28  may control array  23  to emit ultrasound waveforms for neuroprotective purposes and, in some examples, measure reflections of the ultrasound waveforms using the same transducer(s). Alternatively, controller device  28  controls array  23  to emit neuroprotective ultrasound waveforms and imaging ultrasound waveforms using two different sets of waveform emission control parameters. Controller device  28  may control array  23  to alternate between neuroprotective and imaging waveform emissions, in which different ultrasound parameter sets are used to define the neuroprotective waveforms and the imaging waveform. 
     Emitted waveforms may have a frequency ranging between approximately 0.1 MHz and 20 MHz. Neuroprotective ultrasound waveforms may have a relatively low frequency in a range of approximately 0.1 MHz to 5 MHz. In some examples, neuroprotective ultrasound waveforms may be between 0.1 MHz and 1 MHz. In other examples, the frequency range may be between approximately 0.1 MHz to 0.3 MHz to target neurons within the skull. Imaging ultrasound waveforms may have a relatively higher frequency in the range of approximately 2 MHz to 20 MHz. In some examples, imaging ultrasound waveforms may be between approximately 2 MHz and 10 MHz. The frequency ranges for neuroprotective waveforms and imaging waveforms may overlap in some examples, and any reflections received by one or more transducers of array  23  may be measured by system  10  (e.g., controller device  28  or another imaging module) for generating image data of one or more regions within brain  16 . 
     Higher frequency ultrasound waveforms may be used to generate more detailed imaging data than frequencies used to deliver neuroprotective ultrasound waveforms. In this case, controller device  28  may control array  23  to emit distinct neuroprotective waveforms and imaging ultrasound waveforms, which may be delivered simultaneously or in an alternating manner. The imaging waveforms may be delivered by selecting the same or different transducers within array  23  as the transducers selected for delivering neuroprotective waveforms. The imaging waveforms may be less focused than neuroprotective waveforms to obtain a larger view of an anatomical region or focused on a different region of brain  16  than a targeted region receiving neuroprotective energy in order to monitor a functional response at the different region. Neuroprotective energy may be the energy provided by ultrasound waves that protects neurons, such as dopaminergic neurons, from dopamine depleting neurotoxins. 
     Controller device  28 , or a different device, may measure reflections of the imaging waveforms and may generate image data. In some examples, the reflections of the neuroprotective waveforms may be measured in addition to the reflections of the imaging waveforms for collecting data relating to a target region, relating to the pathways  30  and  32 , and/or relating to a functional response (e.g., a brain state that indicates a level of neuron activity) to the neuroprotective waveforms at the selected region intended to receive the neuroprotective effects or a different region (e.g., a target region to which the neuroprotective waveforms are focused). 
     Although controller device  28  may generate image data from reflected ultrasound waves, data indicative of a brain state of a region in brain  16  may be received using other techniques. For example, system  10  may include one or more electrodes configured to receive electrical signals indicative of neuron activity (e.g., an electroencephalogram (EEG). The electrical signals may be received from independent brain activity and/or in response to ultrasound waves or electrical signals delivered to the region of brain  16 . For example, signals indicating an elevated brain state at the selected region may indicate that delivered ultrasound waves are affecting the desired selected region. In this manner, system  10  may utilize alternative sensors and/or delivery modalities from ultrasound transducers in some examples. 
     A targeted region to which neuroprotective ultrasound waves are focused may be different than a region that is imaged. The neuroprotective ultrasound energy may be delivered at the target region while functional imaging is performed at a monitoring region, i.e., a selected region of interest, to measure a change in response to the delivered ultrasound energy. For example, a response to neuroprotective ultrasound energy may include a change in tissue density due to a blood flow change at the selected region or at a different monitoring region. Accordingly, controller device  18  may use ultrasound parameters that cause array  23  to emit imaging waveforms for imaging and include transducer selection, waveform phase, or other parameters that influence focusing of the imaging waveforms. The size of the monitoring region may be the same as or different (e.g., larger or smaller) than the size of the targeted region, and the monitoring region may or may not include the targeted region. The focusing resolution(s) and target(s) for targeted regions for neuroprotective waves and monitoring regions can be defined separately in a menu or set of regions within brain  16  to be tested. Controller device  28  may control array  23  to achieve neuroprotective wave delivery at targeted region(s) to affect selected regions and monitor for a response to therapy at imaging regions selected to correspond to an expected response to the neuroprotective energy delivered to the targeted regions. In some examples, the imaging regions may be the selected regions of brain  16  that include neurons intended to be protected by the neuroprotective ultrasound energy. 
     Array  23  may, in some examples, include dedicated ultrasound transducers that deliver neuroprotective ultrasound waves and dedicated transducers (e.g., imaging transducers) that receive reflected ultrasound waves. Controller device  28  may be configured to control the imaging transducers to operate simultaneously or in alternating fashion with delivery transducers that deliver the neuroprotective ultrasound waves. As such, array  23  may include two or more sub-arrays, which may include one or more dedicated therapy delivery array(s) and one or more dedicated imaging array(s). The functionality of the transducers  24 A- 24 N, however, may be completely programmable and flexible as controlled by controller device  28 . 
     Controller device  28  may be programmed or otherwise receive instructions by another programming device. Controller device  28  may communicate with the programming device via a wired or wireless communication protocol. In addition, or alternatively, controller device  28  may also include a user interface that receives input from a user (e.g., a clinician, technician, or patient  12 ) and/or outputs data related to the obtained information or currently used ultrasound parameter sets or associated programs. In some examples, the user interface includes, for example, a keypad and a display, which may, for example, be a liquid crystal display (LCD) or light emitting diode (LED) display. The keypad may take the form of an alphanumeric keypad or a reduced set of keys associated with particular functions. Controlling device  28  can additionally or alternatively include a peripheral pointing device, such as a mouse or stylus, via which a user may interact with the user interface. In some examples, a display of controller device  28  may include a touch screen display, and a user may interact with controller device  28  via the display. It should be noted that the user may also interact with controller device  28  remotely via a networked computing device. In other examples, controller device  28  may interface with a separate computing device (e.g., a mobile computing device or workstation) that interfaces with the clinician. 
     As described herein, system  10  may be configured to reduce neuron degeneration within brain  16  of patient  12 . For example, system  10  may be configured to deliver, via one or more ultrasound transducers  24 A- 24 N, ultrasound energy focused to a targeted region (e.g., targeted regions  18  and  20 ) of brain  16  of patient  12 . System  10  may deliver the ultrasound energy according to a set of ultrasound parameters selected to cause one or more of ultrasound transducers  24 A- 24 N to generate ultrasound energy that reduces neuron degeneration within a selected region (not shown) of brain  16 . The selected region may be associated with one or both of targeted regions  18  and  20 . In some examples, controller device  28  may include one or more processors that control an ultrasound module to provide signals that modulate the operation of ultrasound transducers  24 A- 24 N. 
     Controller device  28  may also select one or more ultrasound parameters values for the set of ultrasound parameters that at least partially define delivery of ultrasound energy focused to the targeted region(s) of brain  16 . For example, controller device  28  may select the ultrasound parameter values based on one or more selected regions to receive neuroprotective effects of the ultrasound energy and/or one or more targeted regions to which the ultrasound energy is to be focused. In some examples, controller device  28  may automatically select the ultrasound parameter values according to regions of the brain identified by a clinician or other user. In other examples, controller device  28  may select one or more ultrasound parameter values in response to signals received from targeted regions and/or selected regions within brain  16 . Controller device  28  may titrate ultrasound energy to identify appropriate parameter values that may achieve neuroprotective effects for a certain selected region and select those appropriate parameter values, as described in more detail below. Alternatively, controller device  28  may select the ultrasound parameter values based on a program or other instructions received by a clinician or patient. 
     The set of ultrasound parameters may specify one or more aspects of delivery of the neuroprotective ultrasound energy. For example, the ultrasound parameters may define the one or more ultrasound transducers of array  23  that are to deliver ultrasound waves, waveform shape, waveform amplitude, waveform frequency, duty cycle, waveform phase, and start and stop times of ultrasound energy. In this manner, ultrasound parameters may define the ultrasound waves delivered to patient  12  and when each of the ultrasound transducers of array  23  is activated to generate such ultrasound waves. 
     The process of delivering neuroprotective ultrasound energy may also include positioning the one or more ultrasound transducers of array  23  on an external surface of a head (e.g., cranium  14 ) of patient  12  to focus the ultrasound energy from the ultrasound transducers to targeted regions  18  and  20 . In some examples, positioning the one or more ultrasound transducers of array  23  may include positioning transducer substrate  22  on cranium  14  of patient  12 . A clinician or patient  12  may align one or more locations of substrate  22  with landmarks on the head of patient  12 , such as the ears, temples, or other locations. In other examples, substrate  22  may be pre-conformed to cranium  14  such that substrate  22  only fits correctly in one position. In other examples, a clinician or patient  12  may need to place ultrasound transducers  24 - 24 N, either individually or in groups, at the appropriate locations on cranium  14 . Positioning of ultrasound transducers  24 A- 24 N may be performed to focus the ultrasound transducers to a certain targeted region within brain  16 . Positioning ultrasound transducers  24 A- 24 N may be an iterative process in which ultrasound transducers emit imaging waves, detect reflected waves resulting from the emitted imaging waves, and determine that the current ultrasound transducer location is satisfactory or unsatisfactory to focus ultrasound energy to the targeted region. In this manner, the one or more ultrasound transducers  24 A- 24 N may form an array of ultrasound transducers positionable at respective locations on an external surface (e.g., cranium  14 ) of a head of patient  12 . 
     As discussed herein, targeted regions and selected regions of brain  16  may include the same, at least partially overlapping, portions of brain  16  or separate or distinct portions of brain  16 . Targeted regions are those regions of brain  16  to which ultrasound energy is focused. Selected regions of brain  16  are those regions that contain neurons intended to be protected by the neuroprotective ultrasound energy. In other words, a selected region typically includes neurons that would otherwise degenerate due to a neurodegenerative disorder without the delivery neuroprotective ultrasound energy. A targeted region may be the same as a selected region in some examples. In other examples, the targeted region of the brain may include at least a portion of the selected region of the brain such that the targeted region overlaps with the selected region and/or the targeted region and the selected region share at least one common neuron. 
     In another example, a targeted region is different than a selection region of brain  16 , but the targeted region of brain  16  may include neurons that affect different neurons within the selected region of brain  16 . Neurons within brain  16  may be connected to form a brain circuit such that neuron activity in one region of brain  16  affects the activity of another neuron in another different region of brain  16 . In this manner, system  10  may focus ultrasound energy to a targeted region in order to affect, or modulate, neuron activity in a selected region at a different location within brain  16 . Such connections may allow system  10  to provide neuroprotective benefits to neurons within the selected region of brain  16  and limit the exposure of neurons of the selected region to ultrasound waves. In addition, the targeted region of brain  16  may be superficial to an associated selected region of brain  16 . Since system  10  may be able to focus ultrasound waves of lower energy to more superficial neurons (e.g., neurons closer to the surface of scalp  14 ) than deeper neurons, system  10  may focus ultrasound waves with less energy to the more superficial targeted regions of brain  16  in order to affect one or more selected regions deeper within brain  16 . In other words, higher energy ultrasound waves (e.g., lower ultrasound frequencies) may be required to focus ultrasound waves to deeper regions in brain  16  than more superficial regions of brain  16 . 
     In some examples, controller device  28  may select the one or more ultrasound parameters for the set of ultrasound parameters at least partially defining neuroprotective ultrasound energy via an iterative process. This iterative process may be referred to as titrating ultrasound energy. For example, a processor of controller device  28  may be configured to receive a first signal from the selected region of the brain and associate the first signal with a resting state of the selected region of the brain. The first signal may be indicative of reflected imaging ultrasound waves that have reflected off of the selected region of brain  16 . In other examples, the first signal may be indicative of an electroencephalogram (EEG) representative of electrical activity of the neurons within the selected region. In any case, the first signal may be indicative of the resting state of the selected region that occurs without delivery of ultrasound energy. The resting state may be the baseline brain state used to identify an elevated brain state as described below. 
     Controller device  28  may select a first set of ultrasound parameter values as an initial ultrasound parameter set and deliver ultrasound energy to a targeted region (e.g., targeted region  18  or  20 ) of brain  16  according to the initial ultrasound parameter set. The initial ultrasound parameter set may be a predetermined parameter set that may or may not be specific to the location of the selected region in brain  16 . The processor of controller device  28  may then iteratively adjust values of one or more of the ultrasound parameters (e.g., ultrasound wave amplitude, waveform shape, and/or duty cycle) until the processor receives a second signal from the selected region of the brain indicative of an elevated state of the selected region of the brain. The elevated state may indicate that the ultrasound energy is stimulating the neurons of the selected region at too high a level, and the neuron activity associated with neuroprotection may be just below the detected elevated state. A brain state just below the elevated state may be below a perception threshold at which the patient perceives the ultrasound therapy and above an activation threshold at which neurons are activated. However, the activity of the neurons may be insufficient to elevate the brain state of that particular region of the brain. Neuroprotective ultrasound energy may thus protect neurons from dopamine depleting neurotoxins through increased activity, but neuroprotective ultrasound energy may not be configured to produce an immediate therapy or perceivable therapeutic effect reducing symptom frequency or severity. The neuroprotective ultrasound energy is instead configured to protect remaining neurons from further degeneration. In some examples, the neuroprotective ultrasound energy may elicit an increase in the metabolism of affected brain circuits to protect selected regions of the brain from atrophy or degeneration. 
     In response to detecting the elevated state of brain  16 , the processor of controller device  28  may select previous values of the one or more ultrasound parameters as a final ultrasound parameter set. In other words, controller device  28  may use the ultrasound parameters from the last iteration of ultrasound energy that did not result in the elevated state of brain  16  as the final ultrasound parameter set. Controller device  28  may then deliver the neuroprotective ultrasound energy according to the final ultrasound parameter set. In some examples, the neuroprotective ultrasound energy is configured to be below a perception threshold at which patient  12  perceives delivery of the ultrasound energy and also below an activation threshold at which neurons within the selected region of brain  16  are activated. In other examples, the neuroprotective ultrasound energy may be configured to be below either the perception threshold or the activation threshold. In this manner, controller device  28  may request patient feedback during delivery of neuroprotective ultrasound energy to determine if patient  12  can perceive any effects, and controller device  28  may adjust one or more ultrasound parameter values to reduce or eliminate and perceived effects. 
     As described herein, neuroprotective ultrasound energy may be delivered to reduce nerve or neuron degeneration associated with one or more diseases or disorders. For example, the set of ultrasound parameters may be selected to generate ultrasound energy configured to reduce nerve and/or neuron degeneration associated with Alzheimer&#39;s disease, Parkinson&#39;s disease, tremor, or dystonia, dementia, or chronic pain. Each of these diseases or disorders may be associated with typical regions within the brain at which neurons degenerate over time. These typical regions may be identified as the selected regions for neuroprotective ultrasound energy. For example, Parkinson&#39;s disease may be associated with the Substantia nigra and/or subthalamus nucleus. In some examples, targeted regions to which the ultrasound energy is focused may be determined in order to affect the selected regions associated with the disease or disorder of the patient. 
     Neuroprotective ultrasound energy may be delivered to a patient at any time to reduce the degeneration of brain nuclei, fiber tracks and/or neurons. However, early delivery of neuroprotective ultrasound energy may increase the amount of time a patient retains motor function and/or cognitive function. In this manner, a clinician may prescribe neuroprotective ultrasound energy in response to the first diagnosis of a neurodegenerative disease or disorder. The clinician may prescribe neuroprotective ultrasound energy with system  10  concurrently with medication and/or before medication is even prescribed. Since system  10  may operate non-invasively, there may be little to no risk to early delivery of the neuroprotective ultrasound energy. 
     In other examples, a clinician may prescribe neuroprotective ultrasound energy delivery for patients at risk of contracting a neurodegenerative disease and before any disease symptoms occur or the disease can otherwise be diagnoses. For example, the clinician may monitor one or more risk parameters for one or more respective neurodegenerative disease. If one or more risk parameter values exceed the respective threshold for a neurodegenerative disease, the clinician may prescribe neuroprotective ultrasound energy delivery. In some examples, a single risk parameter value exceeding the threshold may be sufficient for neuroprotection. In other examples, a predetermined number of risk parameter values may need to exceed their respective thresholds before a clinician may prescribe neuroprotective ultrasound energy delivery. Example risk factors may include genetic history, environmental conditions predisposing the patient to a neurodegenerative disorder, measured decrease in the volume of a selected region of the brain, age, and/or injuries known to lead to one or more degenerative diseases. 
     System  10  may be configured to deliver neuroprotective ultrasound energy to patient  12  at only certain times of the day. For example, a clinician may prescribe neuroprotective ultrasound energy to be delivered during a sleep period of patient  12  to reduce any impact to daily routine and/or reduce any perceived side attributed to the ultrasound energy. In other examples, patient  12  may need to receive the neuroprotective ultrasound energy at multiple times during the day. The amount of time patient  12  needs to receive neuroprotective ultrasound energy may depend upon the detected progression of the disease or patient feedback. If patient  12  is experiencing a greater number of symptoms, patient  12  may request an increase delivery time for the neuroprotective ultrasound energy each day, for example. 
       FIG. 2  is a conceptual diagram illustrating an example wearable device  40  that includes an array of ultrasound transducers  52  that deliver ultrasound energy to a targeted region of brain  46 . Wearable device  40  may be similar to system  10  of  FIG. 1  and patient  42  may be similar to patient  12 . As shown in  FIG. 2 , wearable device  40  may include substrate  48 , an array of ultrasound transducers  52 , and controller device  50 . Substrate  48 , ultrasound transducers  52 , and controller device  50  may be similar to substrate  22 , ultrasound transducers  24 A- 24 N, and controller device  28 , respectively, of  FIG. 1 . Patient  42  may wear wearable device  40  during a sleep session, when awake at home, or at any other location. 
     Wearable device  40  may represent a helmet, hat, cap, or other article that is configured to be worn over cranium  44  of patient  42 . Substrate  48  may be constructed of one or more types of polymers, fabrics, or other materials. In some examples, the different materials of substrate  48  may be layered. For example, an interior layer may be constructed of a flexible polymer configured to conform to the skin surface of cranium  44 . An exterior layer may be more durable and more rigid than the interior layer to allow a suitable fixation structure for each of transducers  52  and/or controller device  50 . In some examples, breathable fabric may be disposed between the skin of patient  42  and a flexible polymer layer to accommodate patient  42  wearing wearable device  40  for several hours or even longer. Wearable device  40  may be constructed specifically for patient  42  or to be worn by many different patients. 
     Each of ultrasound transducers  52  may be mounted to or embedded at least partially within substrate  48 . The position of ultrasound transducers  52  within substrate  48  may be selected such that each of ultrasound transducers  52  contacts the skin of cranium  44  when wearable device  40  is placed on cranium  44 . In this manner, an energetic surface of the ultrasound transducers  52  may be disposed flush with an interior surface of substrate  48  or protruding from the interior surface of substrate  48 . In general, wearable device  40  may include between two and 1000 ultrasound transducers  52 . In one example, wearable device  40  may include between 5 and 20 ultrasound transducers  52 . Example numbers of ultrasound transducers  52  may be 5, 10, or 20 transducers. In one example, the ultrasound transducers may be replaced with microscopic Capacitive Machined Ultrasound Transducers (CMUTs). The number of CMUTs may be greater than one million in some examples. Groups of CMUTs may be wired in parallel to create functional transducer blocks in which each CMUT of the group behaves identically. The spatial arrangement of the transducers or transducer blocks on substrate  48  may be patient-specific (based on the size and/or shape of a particular patient&#39;s cranium  44  or on an intended target) or may instead be more generic. 
     Each of ultrasound transducers  52  may be identical. Alternatively, some of ultrasound transducers  52  may have a different size, shape, or even be tuned for different ultrasound frequencies than other ones of ultrasound transducers  52 . In this manner, each ultrasound transducer within substrate  48  may be configured for the specific location at which the transducer is disposed within the substrate. The types of ultrasound transducers may be selected to focus to a specific region of brain  46  (e.g., depth of the region and/or volume of the region) and/or based on the thickness of the skull through which the ultrasound waves must penetrate to reach the targeted region. The type of ultrasound transducers  52  may be tailored to patient  42  and/or the targeted regions to which ultrasound energy will be focused. 
     Controller device  50  may also be partially or fully embedded within substrate  48  or otherwise attached to substrate  48 . Controller device  50  may be electrically connected to each of ultrasound transducers  52  and include an ultrasound module configured to energize and/or receive signals from the ultrasound transducers. Controller device  50  may also include a processor configured to control the ultrasound module and perform other tasks related to delivery of neuroprotective ultrasound energy. Controller device  50  may include a power source (e.g., rechargeable and/or replaceable battery) and a user interface that allows a clinician or patient to adjust at least some operations of controller device  50 . 
     A telemetry module within controller device  50  may also allow a programming device to transmit instructions to and/or receive data from controller device  50 . The programming device may be a dedicated handheld computing device, a mobile device (e.g., a mobile phone or tablet computing device), a notebook computer, a workstation, or any other computing device configured to communicate with controller device  50 . In some examples, controller device  50  and/or the programming device may communicate with a remote server or other remove computing device via a network. In this manner, a clinician may remotely interact with the operation of controller device  50 . 
     Although external devices with ultrasound transducers may be used as described herein, ultrasound transducers may be implanted in some examples. For example, some or all of the ultrasound transducers may be implanted beneath the skin of the scalp and external of the cranium during a minimally invasive procedure. A controller device  50  and other electronics may be included within an implantable medical device coupled to the ultrasound transducers such that no percutaneous ports are necessary for operation. Alternatively, one or more percutaneous leads may couple the implanted ultrasound transducers with an external control circuitry. In other examples, the only implanted element may include a positioning device that positions one or more externally placed ultrasound transducers to the head of the patient. For example, one or more small magnets may be implanted beneath the scalp of the patient. A corresponding magnet associated with an external one or more ultrasound transducers (e.g., the corresponding magnet constructed into an array of ultrasound transducers) may then couple to the implanted one or more magnets to maintain proper alignment of the external ultrasound transducers to deliver ultrasound energy to the targeted region of the brain of the patient. 
       FIG. 3  is a conceptual diagram illustrating example ultrasound transducers  60 ,  70 , and  80  that can be used to focus ultrasound energy to a targeted region of a brain. Any of ultrasound transducers  60 ,  70 , or  80  may be implemented in system  10  of  FIG. 1  or wearable device  40  of  FIG. 2 . Transducer  60  is shown having a flat acoustical surface  62  such that emitted waveforms  64  are unfocused. In other words, emitted waveforms  64  may be emitted generally perpendicular from flat acoustical surface  62 . Transducer  70  includes a concave acoustical surface  72  emitting focused ultrasound waves  74  to a particular location at a specified distance from concave acoustical surface  72 . Transducer  80 , having a flat acoustical surface  82 , includes an acoustical lens  84  (e.g., a convex lens) for focusing ultrasound waves  86  to a particular location at a specified distance from flat acoustical surface  82 . 
     Ultrasound transducers of the types illustrated by transducers  60 ,  70 , and  80 , or other types of ultrasound transducers, may be used solely or in any combination in a transducer array for delivering neuroprotective ultrasound energy and/or imaging ultrasound energy. In some examples, certain types of transducers may be used to deliver neuroprotective ultrasound waves and other types of transducers may be used to deliver and/or receive ultrasound waves for imaging or functional diagnostic purposes. The waveforms emitted by a combination of transducers may be focused at a target region using ultrasound parameters such as phase relationships. As used herein, a transducer “array” refers to any n×n array, wherein n may be 1 or greater than 1, the array including multiple transducers or a 1×1 array with a singular transducer. A transducer array is not limited to a linearly arranged array, or an array arranged in rows and columns, but may include, for example, a circular array, a random array or any other arrangement of transducers along a substrate. 
       FIG. 4  is a schematic diagram of example regions and brain circuits within brain  500  of a patient. A first brain circuit  96  shown by a solid line in  FIG. 4  links multiple brain structures  92  (shown as dotted regions). A second brain circuit  98  links brain structures  94  (shown as stripped regions). An ultrasound transducer selection protocol may be defined to select ultrasound transducers that will enable system  10 , for example, to focus neuroprotective ultrasound waveforms on one or more structures  92  and  94  of a respective brain circuit  96  and  98  and along known neural pathways of these circuits. Neuroprotective ultrasound energy may be focused to a target region along a brain circuit in order to affect neurons within a different selected region within the same brain circuit. In other words, brain circuits such as example brain circuits  96  and  98  may allow neuroprotective ultrasound energy to be focused to a targeted region of the brain to affect neurons within a different selected region of the brain. For example, neuroprotective ultrasound waves focused on a superficial region within brain circuit  96  may affect a selected region deep within brain  90  and within the same brain circuit  96 . Alternatively, or additionally, neuroprotective ultrasound waves may be focused to one or more target regions within one or more brain circuits while acquiring functional imaging data to provide detailed diagnostic data of other selected regions within the respective brain circuits. 
     While the examples of  FIG. 4  primarily focus on the brain as the target, it will be understood that some or all of the techniques described herein may be applied to any other area of the anatomy that may be the target of an electrical stimulation therapy, an ultrasound therapy, a drug delivery therapy, or any combination thereof. Such therapies or procedures may be delivered acutely or chronically. A chronic therapy is a therapy used for more than one day, for example, and may be delivered using external and/or implantable therapy delivery devices. 
     Targets for acute or chronic neuroprotective ultrasound stimulation delivery may include but are not limited to, the following: spinal nerves for back pain, intercostal nerves for mastectomy pain, sciatic nerve for muscular constriction, supra/suborbital/infraorbital nerves and trigeminal nerve for facial pain, cranial nerves for cervical pain, median nerve for carpal tunnel, cluneal/iliohypogastric/lateral femoral nerves for pain associated with iliac bone crest harvest, ilioinguinal and iliohypogastric nerves for herniorrhaphy pain, vagus nerve for vagus nerve stimulation for treating epilepsy, hypertension and depression and occipital nerves for chronic migraine. Urinary frequency and urgency, fecal incontinence, chronic pelvic pain, painful bladder syndrome, interstitial cystitis, chronic prostatitis, and sexual dysfunction may be treated with any combination of delivery of ultrasound stimulation to sacral nerves, pudendal nerve and its branches, tibial nerve and its branches, dorsal nerve of clitoris for females, and dorsal nerve of penis for males. In some examples, ultrasonic stimulation may be delivered to excite nerves for exercising muscles following spinal cord injury. Neuroprotective ultrasound energy may be combined with electrical, pharmaceutical or other neuromodulation techniques, and may target a different modulation site. For example, ultrasound modulation of a peripheral nerve site may be combined with electrical stimulation of a central nervous system site or vice versa. 
       FIG. 5  is a block diagram illustrating an example configuration of controller devices  28  or  50   FIGS. 1 and 2 , respectively. In the example of  FIG. 5 , controller device  28  includes processor  100 , memory  102 , ultrasound module  112 , sensor  114 , input devices  108 , output devices  110 , communication module  116 , and power source  118 . In other examples, controller device  28  may include more or fewer components. For example, controller device  28  may include electrodes and sensing circuitry for receiving electrical signals from the brain and generating an EEG from the received signals. In other examples, sensor  114  and/or one or more of input devices  108  or output devices  110  may not be included. 
     In general, controller device  28  may comprise any suitable arrangement of hardware, alone or in combination with software and/or firmware, to perform the techniques attributed to controller device  28  and processor  100  and ultrasound module  112  of controller device  28 . In various examples, controller device  28  may include one or more processors, such as one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. Controller device  28  also, in various examples, may include a memory  102 , such as random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, comprising executable instructions for causing the one or more processors to perform the actions attributed to them. Moreover, although processor  100  and ultrasound module  112  are described as separate modules, in some examples, processor  100  and ultrasound module  112  (or more devices of controller device  28 ) are functionally integrated. In some examples, processor  100  and/or a separate controller for ultrasound module  112  correspond to individual hardware units, such as ASICs, DSPs, FPGAs, or other hardware units. 
     Memory  102  stores information such as instructions and generated data. For example, memory  102  may include delivery programs  104  and patient data  106 . Delivery programs  104  may include instructions (e.g., one or more programs) that define the delivery of neuroprotective ultrasound energy. Each program may include respective a set of ultrasound parameters that defines which ultrasound transducers of an array are active, waveform shape, waveform amplitude, waveform frequency, duty cycle, the waveform phase, the number of waveforms within each burst of waveforms, and the frequency of bursts of waveforms. Each delivery program  104  may also define when the neuroprotective ultrasound energy should be delivered (e.g., certain times of day, duration of delivery, days of the week, etc.). In some cases, the time at which ultrasound energy should be delivered is coordinated with, or otherwise based on, the time of delivery of another therapy, such as the delivery of a medication. Memory  102  may also include programs that define determination of appropriate ultrasound parameters, ultrasound imaging processes, and/or the determination of brain states of selected regions of the brain. 
     Patient data  106  may include data generated during the operation of controller device  28 . For example, patent data  106  may include times and durations at which neuroprotective ultrasound energy was delivered, detected brain states, targeted regions and selected regions, imaging information from reflected ultrasound waves, EEG information, or any other data. Processor  100  may, in some examples, output patient data  106  for presentation to the user via output devices  110  and/or via for communication by communication module  116  to a different computing device. Patient data  106  may also include any detected errors that occurred during the delivery of neuroprotective ultrasound energy. 
     Ultrasound module  112  is configured to energize any of ultrasound transducers  24 A- 24 N according to the ultrasound parameters stored in delivery programs  104 . For example, processor  100  may control ultrasound module  112  to apply electrical signals to one or more of ultrasound transducers  24 A- 24 N to generate neuroprotective ultrasound waves. Alternatively, ultrasound module  112  may independently control the ultrasound transducers using the stored ultrasound parameters. In some examples, ultrasound module  112  may also receive signals generated by one or more of ultrasound transducers  24 A- 24 N in response to detecting reflected waves. Ultrasound module  112  may then generate data indicative of the received signals for purposes such as generating imaging information regarding targeted regions and/or selected regions within the brain. 
     Sensor  114  may be a temperature sensor that detects the temperature of tissue adjacent to controller device  28  and/or the temperature of the skin adjacent to one or more of ultrasound transducers  24 A- 24 N. Processor  100  may monitor a signal from sensor  114  and terminate the delivery of ultrasound energy if the signal indicates that the temperature exceeds a predetermined threshold. Processor  100  may also redeliver ultrasound energy in response to determining that the temperature falls back below the threshold. In addition, or alternatively, sensor  114  may include one or more accelerometers that generate a signal indicative of patient movement. Processor  100  may monitor the motion of the patient to determine when the patient falls asleep and may begin delivery of neuroprotective ultrasound energy in response to determining that the patient is asleep. In this manner, processor  100  may limit the ultrasound energy from potentially disrupting sleep. In other examples, controller device  28  may include an electroencephalogram (EEG) module configured to receive electrical signals from electrodes placed on the cranium of the patient and generate EEG signals. Processor  100  may determine brain states (e.g., resting states or elevated states) according to the generated EEG signals. In one example, processor  100  may utilize the EEG signals instead of, or in addition to, the accelerometer signal(s) to determine when the patient has fallen asleep so that ultrasound energy may be delivered when the patient is asleep. 
     Controller device  28  may be configured to receive inputs from a user. Input devices  108  may include one or more buttons, keypads, touch-sensitive screen, pointing device, or any other input device. Output devices  110  may include one or more lights, a speaker, and a display, such as a liquid crystal (LCD), light-emitting diode (LED), or cathode ray tube (CRT). In some examples the display may be a touch screen. Output devices  110  may thus be configured to output information (e.g., the status of neuroprotective ultrasound energy delivery and/or patient data  106 ) to a user. Processor  100  may be configured to control input devices  108  and output devices  110 . For example, processor  100  may control output device  104  to present an indication of whether or not ultrasound energy is being delivered. Processor  100  may also control output devices  110  to present any information associated with the delivery of ultrasound energy or the operational status of controller device  28 . In some examples, processor  100  may control output devices  110  to indicate any malfunction of a transducer or controller device  28 . In some examples, the combination of input devices  108  and output devices  110  may be referred to as a user interface for controller device  28 . 
     Communication module  116  may be configured to receive data from another computing device and/or transmit data to another computing device. Communication module  116  may be configured to communicate via wired or wireless communication protocols for direct communication or via a network. Examples of wireless communication techniques that may be employed to facilitate communication between controller device  28  and another computing device include RF communication according to the 802.11 or Bluetooth specification sets, infrared communication, e.g., according to the IrDA standard, or other standard or proprietary telemetry protocols. 
     Power source  118  delivers operating power to the components of controller device  28 . Power source  118  may include a battery and a power generation circuit to produce the operating power. In some examples, the battery may be rechargeable to allow extended operation. In other examples, power source  118  may be configured to accept replaceable batteries or receive power from an alternating current (AC) outlet. 
       FIG. 6  is a flow diagram that illustrates an example process for determining a set of ultrasound parameters that at least partially define ultrasound energy deliverable to a targeted region of a brain of a patient. As described in  FIG. 6 , processor  100  of controlling device  28  may be used to determine ultrasound parameters for use in delivering neuroprotective ultrasound energy to a targeted region of brain  16 . However, in other examples, other devices or systems, such as wearable device  40 , may be used to perform such a process. In some examples, controlling device  28  may perform the process of  FIG. 6  in response to a single input received from a patient requesting the determination of an appropriate set of ultrasound parameter (e.g., controlling device  28  may autonomously determine the set of ultrasound parameters). 
     Processor  100  may select a region (e.g., a selected region) that includes neurons that may be subject to degeneration from a neurodegenerative disease. For example, the substantia nigra (SN) may be the selected region for a patient diagnosed with Parkinson&#39;s disease. The selected region may be determined by processor  100  or a user (e.g., a clinician or user) based on a neurodegenerative disease for which the patient has been diagnosed or is otherwise at risk. Processor  100  may receive a first signal from the selected region of brain  16  of patient  12  ( 120 ). The first signal may be received without delivery of ultrasound energy affecting the neurons in the selected region. The first signal may be representative of an EEG of the selected region or any other diagnostic modality. Processor  100  may then associate the first signal with a resting state of the selected region of brain  16  ( 122 ). 
     Processor  100  may then select a first set of ultrasound parameter values as an initial ultrasound parameter set ( 124 ). The initial ultrasound parameter set may be generic for any selected regions or targeted regions or specifically tailored for a respective selected region or targeted region. Processor  100  may then control ultrasound module  112  to deliver ultrasound energy to a targeted region (e.g., targeted region  18  or  20 ) of brain  16  associated with the selected region of brain  16  ( 126 ). Processor  100  may then monitor the brain state of the selected region in response to delivering the ultrasound energy (e.g., during delivery or after terminating delivery) ( 128 ). If processor  100  has not sensed an elevated brain state (“NO” branch of block  128 ), processor  100  may adjust one or more parameter values to increase the ultrasound energy ( 130 ) and again deliver ultrasound energy with the new parameter values ( 126 ). 
     If processor  100  senses an elevated brain state (“YES” branch of block  128 ), processor  100  may select the previous ultrasound parameter values as the final ultrasound parameter set ( 132 ). The previous ultrasound parameter values may be those values that defined the most recent ultrasound energy that did not cause the elevated brain state. Processor  100  may then store the final ultrasound parameter set in memory  102  for subsequent delivery of neuroprotective ultrasound energy. Processor  100  may also control ultrasound module  112  to deliver neuroprotective ultrasound energy to the targeted region of brain  16  according to the final parameter set ( 134 ). 
     Although the process of  FIG. 6  is described as using EEG information to determine brain state, the brain state of patient  12  may be determined using different modalities in other examples. For example, physiological monitoring or imaging sources may include, but are not limited to, reflected ultrasound waves, magnetic resonance imaging (MRI), functional MRI, positron emission tomography (PET), computed tomography (CT), electromyogram (EMG), accelerometer and/or electroencephalogram (EEG). Functional imaging, anatomical imaging, and/or electrophysiological measurements can be used by processor  100  to identify a target region and/or determine brain states of selected regions to determine appropriate ultrasound parameter values for neuroprotective ultrasound energy delivery. 
       FIG. 7  is a flow diagram that illustrates an example process for delivering ultrasound energy focused to a targeted region of a brain of a patient to reduce neuronal degeneration within a selected region of the brain. As described in  FIG. 7 , processor  100  of controlling device  28  may be used to deliver neuroprotective ultrasound energy to a targeted region of brain  16 . However, in other examples, other devices or systems, such as wearable device  40 , may be used to perform such a process. 
     Processor  100  may determine a selected region of brain  16  in which to reduce neuronal or neuron degeneration ( 140 ). Processor  100  may determine the selected region by retrieving instructions from memory  102  or by referencing the diagnosed neurogenerative disease. Processor  100  may then select a set of ultrasound parameter values that focus neuroprotective ultrasound energy to a targeted region of brain  16  associated with the selected region of brain  16  ( 142 ). Using the set of ultrasound parameter values, processor  100  may then control ultrasound module  112  to deliver ultrasound energy focused to the targeted region of brain  16  to reduce neuronal degeneration within the selected region of brain  16  ( 144 ). 
     System  10  or wearable device  40  may be configured to reduce the degeneration of neurons caused by Parkinson&#39;s disease. For example, neuroprotective ultrasound energy may be relatively low energy ultrasound waves configured to protect dopaminergic neurons in the substantia nigra. This result may be caused by neuron activity protecting the neurons from dopamine depleting neurotoxins. The substantia nigra (SN) may be the selected region and the subthalamic nucleus (STN) may be the targeted region, in one example. Targeted regions and selected regions may include one or both of the SN and STN in another example. In addition, or alternatively, a selected region and/or a targeted region may include the globus pallidus inferior (GPI). For Alzheimer&#39;s disease, the selected region and/or targeted region may include the hippocampus, for example. 
     The techniques of this disclosure may be implemented in a wide variety of computing devices, medical devices, or any combination thereof. Any of the described units, modules or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components. 
     The disclosure contemplates computer-readable storage media comprising instructions to cause a processor to perform any of the functions and techniques described herein. The computer-readable storage media may take the example form of any volatile, non-volatile, magnetic, optical, or electrical media, such as a RAM, ROM, NVRAM, EEPROM, or flash memory that is tangible. The computer-readable storage media may be referred to as non-transitory. A server, client computing device, or any other computing device may also contain a more portable removable memory type to enable easy data transfer or offline data analysis. 
     The techniques described in this disclosure, including those attributed to system  10 , wearable device  40 , and various constituent components, may be implemented, at least in part, in hardware, software, firmware or any combination thereof. For example, various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components, remote servers, remote client devices, or other devices. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry. 
     Such hardware, software, firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any of the described units, modules or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components. 
     The techniques or processes described in this disclosure may also be embodied or encoded in an article of manufacture including a computer-readable storage medium encoded with instructions. Instructions embedded or encoded in an article of manufacture including a computer-readable storage medium encoded, may cause one or more programmable processors, or other processors, to implement one or more of the techniques described herein, such as when instructions included or encoded in the computer-readable storage medium are executed by the one or more processors. Example computer-readable storage media may include random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, a hard disk, a compact disc ROM (CD-ROM), a floppy disk, a cassette, magnetic media, optical media, or any other computer readable storage devices or tangible computer readable media. The computer-readable storage medium may also be referred to as storage devices. 
     In some examples, a computer-readable storage medium comprises non-transitory medium. The term “non-transitory” may indicate that the storage medium is not embodied in a carrier wave or a propagated signal. In certain examples, a non-transitory storage medium may store data that can, over time, change (e.g., in RAM or cache). 
     Various examples have been described herein. Any combination of the described operations or functions is contemplated. These and other examples are within the scope of the following claims.