Treatment Device

Abstract

A method and a treatment device configured to be worn on the head are disclosed. The treatment device includes a frame configured with emitters that deliver at least one radiation modality to a volume within the head, irradiating the brain with the emitters to activate drugs or pharmaceuticals. The device may be a helmet that includes emitters that are adjustable with respect to orientation and position around the head. A method is further included for creating a patient-specific customized treatment device by acquiring a three-dimensional (or 3D) topology of the head using an imaging system.

Description

[Technical field]

[0001] The present invention relates to therapeutic devices, uses of therapeutic devices, and manufacture of therapeutic devices, and in particular to the treatment of brain disorders. [Background technology]

[0002] Treatment of the mammalian brain for disorders, disease, injury, and research is complicated by the brain's complexity, the protective skull, and the selective permeability of a sieve-like layer of tissue called the blood-brain barrier (BBB), which surrounds each blood vessel and separates the contents of those vessels from the brain's neurons.

[0003] Drugs introduced into the bloodstream to treat the brain are systemic to the circulatory system of the entire body; once they enter the blood vessels of the brain, they cross the BBB and are distributed throughout the brain, with little control over the location or timing of their activation. Systemic administration of drugs targeted to specific regions of the brain can produce deleterious side effects in non-targeted regions of the brain and body.

[0004] To remedy at least some of these problems, techniques are developed to deliver different types of radiation to intracranial volumes. To date, these devices are typically applied to the head by bulky instruments while the participant is immobilized. The individual receiving the radiation is mechanically transported to the area of ​​the instrument where the radiation is delivered. This approach has the disadvantage that such instruments are large, expensive, located in clinics, and in high demand, resulting in long wait times between successive applications. The treatments are burdensome for the participants, and it may be practically impossible to apply continuous or semi-continuous or on-demand signals to specific volumes of the brain over long periods of time.

[0005] Additionally, instruments that deliver radiation to specific volumes of the brain often require surgical attachment of a stereotactic frame to the participant's head to immobilize the head during radiation delivery, which can be uncomfortable and undesirable for the participant, poses surgical risks, and adds cost.

[0006] There is a need for a therapeutic device that can deliver ultrasonic pressure and / or photon radiation and / or magnetic fields to specific intracranial volumes without the drawbacks of bulky instruments, implants, or indwellings, that is capable of continuous, semi-continuous, or on-demand use, that can be conveniently reconfigured for alternative intracranial volumes, that is widely available, convenient to maintain, and relatively inexpensive. Summary of the Invention

[0007] According to one example, a therapeutic device is provided, the therapeutic device may be configured to be mounted on a head and may include a frame configured to be mounted on the head and a plurality of emitters supported by the frame, the plurality of emitters configured to deliver a first radiation modality to a volume within the head, the plurality of emitters configured to activate a drug within the volume irradiated by the emitters.

[0008] According to another example, a treatment device is provided that can be configured for mounting to a head and can include a frame configured for mounting to the head and a plurality of emitters supported by the frame, each emitter configured to deliver at least one radiation modality to a volume within the head, the treatment device configured to allow an orientation and / or position of the at least one emitter relative to the frame to be adjustable, and the plurality of emitters configured to deliver radiation to a common volume within the head.

[0009] According to another example, a method of manufacturing a customized head mounted therapy device is provided, the method including imaging a head to determine a three-dimensional topology of the head, identifying at least one designated volume within the head to be irradiated by a plurality of emitters, determining a desired orientation of the at least one emitter relative to the designated volume, and manufacturing a customized frame configured to be mounted on the head, the customized frame configured to support the at least one emitter such that when the customized frame is mounted on the head, the at least one emitter is positioned in the desired orientation relative to the designated volume within the head.

[0010] According to another example of the present invention, there is provided a method of treating a brain disorder in a subject in need thereof, the method comprising applying a treatment device described herein to the subject's head.

[0011] It is recognized that the terms "comprise, comprise, and include" may have exclusive or inclusive meanings in various jurisdictions. For purposes of this specification, unless otherwise noted, these terms are intended to have an inclusive meaning, that is, they are meant to include the recited components to which their usage directly refers, and possibly other unspecified components or elements as well.

[0012] The reference to any document in this specification is not an admission that it is prior art, that it may be usefully combined with other documents, or that it forms part of the general general knowledge. [Brief description of the drawings]

[0013] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate examples of the present invention and, together with the general description of the invention given above and the detailed description of the examples given below, serve to explain the principles of the invention. [Figure 1A] FIG. 1 illustrates an example of a treatment device. [Figure 1B] FIG. 2 illustrates an example of an emitter. [Diagram 2] FIG. 13 illustrates a further example of a treatment device. [Diagram 3] FIG. 13 illustrates a further example of a treatment device. [Figure 4] FIG. 13 illustrates a further example of a treatment device. [Diagram 5] FIG. 13 illustrates a further example of a treatment device. [Figure 6] 1A-1C illustrate a method for manufacturing a treatment device. [Figure 7] FIG. 1 illustrates an example of a treatment device. [Figure 8] FIG. 1 shows recordings made by hydrophone. [Figure 9] FIG. 2 is a contour plot showing measured sound pressure levels. [Figure 10] FIG. 2 is a contour plot showing measured sound pressure levels. [Figure 11] FIG. 13 illustrates the desired orientation of multiple emitters relative to a phantom head. [Figure 12] FIG. 13 shows a treatment device on a phantom head. [Figure 13] FIG. 13 shows a treatment device on a phantom head. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] 1A illustrates an example of a therapeutic device 100. The therapeutic device 100 includes a frame 103 configured to be worn on the head of a user 101. The frame 103 supports a plurality of emitters 104 configured to deliver at least one radiation modality, shown generally as a beam 105, to a volume 107 within the head of the user 101. The plurality of emitters 104 are configured to activate an agent within the volume 107 irradiated by the plurality of emitters 104. The agent may be thermally activated, mechanically activated, and / or magnetically activated. For example, the agent may be a thermally activated liposome.

[0015] The therapy device 100 further includes (or is in operative communication with) a control circuit 90 that is used to control the operation of the emitter 104 , and a power circuit 95 that provides power to the therapy device 100 .

[0016] As used herein, "radiation" refers to the emission, transmission, and / or propagation of energy in the form of waves or particles, including acoustic radiation (such as ultrasound radiation) and electromagnetic radiation (such as infrared radiation). The radiation modality emitted by the multiple emitters 104 may vary depending on the application of the therapeutic device 100 (e.g., the type of agent activated within the volume 107). For example, the multiple emitters 104 may be configured to emit ultrasound / focused ultrasound, electromagnetic radiation (such as infrared or near infrared radiation), or a magnetic field. Any or all of the emitters 104 may be tunable, as described in more detail below.

[0017] In some examples, the emitter 104 is selected from an acoustic emitter, an ultrasonic emitter, an electromagnetic emitter, an optical emitter, a radio frequency emitter, a magnetic emitter, and / or a magnetic field emitter. A single emitter 104 and its emission 105 are shown in FIG.

[0018] In some examples, the frame 103 can be selected from a group including a permanent frame, an adjustable frame, a custom frame, a flexible frame, a rigid frame, a metal frame, a polymer frame, a composite frame, an additively manufactured frame, and / or a 3D printed frame.

[0019] The treatment device 100 shown in Figure 1A includes emitters 104 positioned around a frame 103, such that an irradiated volume 107 receives radiation from each emitter 104. This arrangement reduces the amount of radiation received by off-axis volumes within the head of the wearer 101. This improves the precision of the treatment and reduces potentially harmful outcomes, such as thermal damage, that may occur when non-target volumes are irradiated. The emitters 104 are typically positioned around the frame 103 such that the beams 105 are approximately orthogonal to the target volume 107.

[0020] It should be noted that the orientation and shape of radiation by beam 105 shown in Figure 1A is schematic, and that the actual shape of the radiation beam emitted by each emitter 104 may have a more complicated path from emitter 104 to target volume 107. For example, ultrasound radiation may reflect and / or refract between or through different tissues in the head of user 101 due to differences in impedance. The front of beam 105 also spreads out, making its orientation somewhat unclear.

[0021] In some examples, the emitters 104 are positioned around the frame 103 and their radiation is focused, defocused, orthogonal, collinear, overlapping, intersecting, and / or superimposed.

[0022] In some examples, the multiple emitters 104 can be configured in an array. In some examples, the array of emitters is selected from the group including a sparse array, a dense array, an array of less than 3 emitters, an array of less than 10 emitters, an array of less than 20 emitters, an array of less than 50 emitters, an array of less than 100 emitters, and / or an array of less than 300 emitters. A sparse array of emitters can be advantageous in that a specified volume within the skull is not occupied by a single emitter, in which case targeting will be highly dependent on the placement of the treatment device. There may be a trade-off between the number of emitters 104 and the illumination volume 107, the tolerance for aberrations in the illumination field due to incomplete coverage of the head, the physical weight of the treatment device, and the manufacturing costs of the treatment device.

[0023] In some applications of the therapeutic device 100, the volume 107 irradiated by the emitter 104 may include tissue, scalp, bone, dura mater, arachnoid mater, pia mater, brain tissue, gray matter, white matter, blood vessels, vasculature, neurons, glial cells, cerebral hemispheres, cerebellar hemispheres, lobes, frontal lobe, parietal lobe, temporal lobe, occipital lobe, cortex, frontal cortex, motor cortex, sensory cortex, occipital cortex, insular cortex, temporal cortex, cerebellum, brainstem, midbrain, pons, medulla oblongata, diencephalon, thalamus, hypothalamus, striatum, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra, amygdala, hippocampus, drugs, malignant tissue, tumors, diseased tissue, gliosis, neuromodulatory drugs, cytotoxic drugs, contrast agents, ultrasound responsive materials, ultrasound labile materials, light responsive materials, magnetic field responsive materials, phase The particles may be one or more of: a variable material, a bubble, a gas bubble, a liquid bubble, a perfluorocarbon, a lipid, a membrane, a micelle, a lipid bilayer, a liposome, a solid lipid nanoparticle, a cubosome, a solid particle, a solid nanoparticle, a hollow nanoparticle, a metal particle, a non-metal particle, a magnetic particle, a ferromagnetic particle, a plasmonic particle, a surface enhanced plasmonic particle, a plasmonic nanoparticle, a gold particle, a gold nanoparticle, an inorganic particle, an amorphous particle, a crystalline particle, a semi-crystalline particle, a lipid linked particle, a lipid encapsulated particle, a molecule, a protein, an antibody, a peptide, a nucleic acid, a deoxyribose nucleic acid, a ribose nucleic acid, a genetic construct, a gene, a genetic sequence, a vector, a virus.

[0024] In some examples, the volume 107 irradiated by the multiple emitters 104 may be greater than 1 mm 3 Less than 5mm 3 Less than 10mm 3 Less than 20mm 3 Less than 50mm 3 Less than 100mm 3 Less than 200mm 3 Less than 500mm 3 Less than 1,000mm 3 Less than 2,000mm 3 Less than 5,000mm 3 Less than 10,000mm 3 Less than 50,000mm 3 Less than 100,000mm 3 Less than 500,000mm 3 Less than 1,000,000 mm 3Less than and / or 2,100,000 mm 3 is less than.

[0025] In some examples, the shape of volume 107 is regular, irregular, spherical, ovoid, and / or a combination or superposition of shapes.

[0026] 1A, only one volume 107 is shown, but this is not intended to be limiting. Some applications of the treatment device 100 irradiate multiple volumes within the head of the wearer 101. In some examples, the volumes 107 are a number of overlapping or non-overlapping volumes selected from the group including: 1, 2, 3, 4, 5, 6, 7, less than 20 designated volumes, less than 100 designated volumes, and / or less than 300 designated volumes.

[0027] In some examples, the emitter 104 is an acoustic emitter and is selected from the group including an ultrasound emitter, an ultrasound transducer, and / or a piezoelectric transducer.

[0028] In some examples, the emitter 104 may be configured to operate at frequencies of approximately 200 kHz, 300 kHz, 400 kHz, 500 kHz, 600 kHz, 700 kHz, 800 kHz, 900 kHz, 1 MHz, 2 MHz, 3 MHz, 4 MHz, 5 MHz, 6 MHz, 7 MHz, 8 MHz, 9 MHz, 10 MHz, 11 MHz, 12 MHz, 13 MHz, 14 MHz, 15 MHz, 16 MHz, 17 MHz, 18 MHz, 19 MHz, 20 MHz, 21 MHz, 22 MHz, 23 MHz, 24 MHz, 25 MHz, 26 MHz, 27 MHz, 28 MHz, 29 MHz, 30 MHz, 31 MHz, 32 MHz, 33 MHz, 34 MHz, 35 MHz, 36 MHz, 37 MHz, 38 MHz, 39 MHz, 40 MHz, 41 MHz, 42 MHz, 43 MHz, 44 MHz, 45 MHz, 46 MHz, 47 MHz, 48 MHz, 49 MHz, 50 MHz, 51 MHz, 52 MHz, 53 MHz, 54 MHz, 55 MHz, 56 MHz, 57 MHz, 58 MHz, 59 MHz, 60 MHz, 61 MHz, 62 MHz, 63 MHz, 64 MHz, 65 MHz, 66 MHz, 67 MHz, 68 MHz, 69 MHz, 70 MHz, 71 MHz, 72 MHz, 73 MHz, 74 MHz, The ultrasonic radiation is emitted at a frequency selected from the group including 3 MHz, 24 MHz, 25 MHz, 26 MHz, 27 MHz, 28 MHz, 29 MHz, 30 MHz, 31 MHz, 32 MHz, 33 MHz, 34 MHz, 35 MHz, 36 MHz, 37 MHz, 38 MHz, 39 MHz, 40 MHz, 41 MHz, 42 MHz, 43 MHz, 44 MHz, 45 MHz, 46 MHz, 47 MHz, 48 MHz, 49 MHz, or about 50 MHz. In one example, the frequency is about 1 MHz. In another example, the frequency is about 300 kHz. In another example, the frequency is about 600 kHz. In other examples, the ultrasonic signal is provided at a frequency between about 50 MHz and about 100 MHz, i.e., about 50 MHz, 55 MHz, 60 MHz, 65 MHz, 70 MHz, 75 MHz, 80 MHz, 85 MHz, 90 MHz, 95 MHz, or about 100 MHz.

[0029] In some examples, the emitter 104 may have a power rating of 100 Watts / cm 2 Less than 50 watts / cm 2 Less than 10 watts / cm 2 Less than 1 watt / cm 2 Less than 0.1 watts / cm 2 Less than 0.01 watts / cm 2 The ultrasonic radiation is emitted at an intensity selected from the group including:

[0030] An emitter 104 delivering ultrasound or other acoustic radiation to an intracranial volume 107 can enable imaging of the brain, damaging portions of the brain, damaging malignant tissue in the brain, activating neurons in the brain, repairing damage to the brain, increasing the permeability of the BBB for delivery of substances to the brain, and activating acoustically responsive drugs to specific regions of the brain. The use of ultrasound focused to specific intracranial volumes can provide a method of applying acoustic pressure to specific volumes of brain tissue, including neurons and blood vessels, within the skull without the need for open craniotomy.

[0031] 1A depicts the treatment device 100 on a live human head, but this is not intended to limit the use of the treatment device 100. In some applications, the wearer's head may be one or more of a model, phantom, living body, individual, cadaver, specimen, animal, primate, human, non-human primate, dog, sheep, horse, cow, mouse, and / or rat head.

[0032] The control circuitry 90 and power circuitry 95 may be worn on the head, tethered, and / or in wireless communication with the therapy device 100. The control circuitry 90 and / or power circuitry 95 may include and / or use power sources, batteries, cables, electronic circuits, optoelectronic circuits, integrated circuits, microcircuits, microprocessors, electronic memory, electronic components, telecommunications, global positioning systems, Bluetooth, radios, software, firmware, internet connections, software, firmware, code, operating systems, applications, protocols, and / or internet protocols.

[0033] In one example, the therapy device can communicate with an external control and power unit (e.g., a small backpack unit) that incorporates one or more of a power source, electronics, motion sensors, GPS telemetry, and internet connectivity.

[0034] 2 illustrates a treatment device 200 including a frame 203, a first plurality of emitters 204 configured to emit radiation of a first modality (shown as beam 205), and a second plurality of emitters 214 configured to emit radiation of a second modality (shown as beam 215). Treatment device 200 may alternatively include a single second emitter 214 configured to emit radiation of the second modality in addition to the first plurality of emitters 204. The first plurality of emitters 204 and the second plurality of emitters 214 (or second emitter 214) are configured to deliver radiation to a volume 207 within the head of user 101.

[0035] The therapy device 200 may also include a third plurality of emitters 224 (or third emitters 224) configured to emit radiation of a third modality (shown as beam 225). For example, the first plurality of emitters 204 may be configured to emit ultrasound / focused ultrasound radiation, the second plurality of emitters 214 may be configured to emit electromagnetic radiation, and the third plurality of emitters 224 may be configured to emit a magnetic field. Each emitter (or emitters) may all be configured to deliver radiation to a volume 207 within the head of the wearer 101 and may be configured to activate a drug within the volume 207.

[0036] In some examples in which the treatment device 200 is configured to activate an agent (such as a liposome) within the target volume 207, the emitters 204, 214, and 224 (if applicable) of the treatment device 200 may be configured such that the emitters of either modality deliver a sub-threshold radiation dose to the target volume 207, but the emitters of both (or all) modalities deliver a threshold radiation dose to the target volume 207.

[0037] For example, the treatment device 200 may include a first plurality of emitters 204 configured to emit focused ultrasound radiation and a second plurality of emitters 214 configured to emit electromagnetic radiation. The net radiation of the ultrasound emitters 204 may be below a threshold required to activate a drug in the volume 207. Similarly, the net radiation of the electromagnetic radiation emitters 214 may also be below a threshold required to activate a drug in the volume 207. However, the combined net radiation of the ultrasound emitters 204 and the electromagnetic radiation emitters 214 may be above the threshold required to activate a drug in the volume 207.

[0038] The use of various radiation modalities that are individually below the threshold required to activate agents within volume 207 improves participant safety by reducing the risk of irradiating and damaging off-axis or non-target volumes within the user's head. For example, liposomes within volume 207 may be thermally activated. Thermal damage may occur from the net radiation required to thermally activate the liposomes if the intended radiation is misdirected into volume 207. Splitting the net radiation into two or more sub-threshold modalities reduces the amount of harmful radiation that off-target volumes irradiated by the emitters of a given modality will receive if those emitters are somehow misaligned or misconfigured. This significantly reduces the chance of thermal or other damage due to the relatively low power of a single radiation modality.

[0039] In contrast, when the emitters of each modality are precisely aligned and properly configured, volume 207 receives a combination of radiation from each modality, thereby providing a threshold amount of radiation to the agent within volume 207 .

[0040] While the above examples use radiation of two modalities, the therapy device 200 may also include emitters of three modalities (e.g., ultrasound / focused ultrasound, electromagnetic radiation, and magnetic fields), where radiation from a single modality is below the threshold, but the collective modalities are above the threshold dose. When using three modalities, it may be necessary for emitters of all three modalities to deliver radiation to a common volume to provide the threshold dose. In other examples, emitters of only two of the three modalities may be required to provide the threshold dose to the volume 207.

[0041] Although the emitters are configured to deliver radiation to a common volume, the individual volumes irradiated by the emitters of each modality may differ in size, shape, and location. For example, a first plurality of emitters may be used to deliver diffuse sub-threshold electromagnetic radiation (e.g., infrared radiation) to a relatively large volume in the head. A second plurality of emitters may be used to deliver sub-threshold focused ultrasound radiation to a much smaller volume that at least partially overlaps or intersects with the relatively large volume. The intersection of the larger and smaller volumes is a common volume that receives a combination of diffuse electromagnetic radiation and focused ultrasound radiation. The therapeutic device 200 does not necessarily require multiple emitters of different modalities. For example, the therapeutic device 200 may include a first plurality of emitters configured to emit radiation of one modality and a single emitter configured to emit radiation of a second modality. The therapeutic device 200 may include a single emitter configured to emit radiation of a third modality.

[0042] The use of subthreshold modalities is not limited to applications in which drugs or liposomes are activated within the irradiated volume of the head. For example, a therapy device including emitters with various subthreshold modalities can be used for neurotherapy applications. Neural tissue within the irradiated volume may require a certain power as part of the neurotherapy. The emitters can be configured such that the sum of the different modalities is sufficient to provide the required power, but the power of any one modality is insufficient.

[0043] There are also no limitations on the various combinations of modalities required to provide the threshold dose or sufficient power. For example, a therapy device may include emitters of three different radiation modalities, and a combination of any two modalities may be sufficient to provide the required dose. Alternatively, all three modalities may be required to provide the required dose.

[0044] Additionally, the therapy device 200 may include emitters of two or more different modalities, each individual modality sufficient to provide the required threshold dose or required power, depending on the application of the therapy device.

[0045] The treatment device 200 may include emitters of at least the following modalities: Ultrasonic emitters, Electromagnetic emitters, Magnetic field emitters, Combination of ultrasonic and electromagnetic emitters, Combination of ultrasonic and magnetic field emitters, Combination of electromagnetic and magnetic field emitters, A combination of ultrasonic, electromagnetic and magnetic field emitters.

[0046] Any or all of the emitter 204 and / or the second emitter and / or the third emitter may be tunable as described below.

[0047] The orientation and number of first, second and / or third emitters 204, 214, and 224 can be positioned to intersect their delivered radiation and apply effective acoustic pressure and / or photon illumination and / or radio frequency radiation and / or magnetic field to a specified volume 207 within the head. Calculations can be based on 3D finite element analysis models, CT scans of human cadavers and phantom models, measurements, and MRI thermal images such that the radiation distribution inside the skull is mapped and predictable within specified tolerances.

[0048] In some examples of the treatment device 200, the electromagnetic emitter includes a lamp, a light emitting diode, a laser, a lens, a transmitter, an antenna, and / or a coil.

[0049] In some examples, the electromagnetic emitter emits electromagnetic radiation at a wavelength selected from the group including narrowband, broadband, monochromatic, visible, infrared, and / or near infrared.

[0050] In some examples, the electromagnetic emitter emits radio frequency electromagnetic radiation at wavelengths selected from the group including narrowband, broadband, shortwave, longwave, and / or microwave.

[0051] In some examples, the electromagnetic emitter has a power rating of 10 Watts / cm 2 Less than 1 watt / cm 2 Less than 0.1 watts / cm 2 Less than 0.01 watts / cm 2 Less than 0.001 watts / cm 2 Less than 0.00001 watts / cm 2 The electromagnetic radiation is emitted at an intensity selected from the group including:

[0052] In some examples, the electromagnetic emitter has a power rating of 10 Watts / cm 2 Less than 1 watt / cm 2 Less than 0.1 watts / cm 2 Less than 0.01 watts / cm 2 Less than 0.001 watts / cm 2 Less than 0.00001 watts / cm 2The radio frequency electromagnetic radiation is emitted at an intensity selected from the group including:

[0053] The use of electromagnetic emitters may enable the delivery of light-responsive drugs to areas of the brain, activation of neurons within the brain, and / or repair of brain damage.

[0054] In some examples of the treatment device 200, the magnetic field emitters can include coils, magnets, electromagnets, permanent magnets, inductors, and / or induction coils.

[0055] The use of magnetic field emitters may enable imaging of the brain, stimulation of neurons in the brain, and / or activation of magnetically responsive drugs to regions of the brain.

[0056] Without being bound by any particular theory, the use of a therapeutic device that delivers acoustic radiation, electromagnetic radiation, and / or magnetic fields to a designated volume within the skull can be used for one or more of the following purposes: i. Tissue damage ii. Opening of the blood-brain barrier iii. Activation of specific circuits in the brain a. Tissue modulation, including i. Contrast agents ii. Neuromodulatory drugs iii. Cytotoxic drugs b. Activation of acoustic and / or photon and / or radio frequency and / or magnetic sensitive drugs; i. Degenerative diseases (e.g., Parkinson's disease, Alzheimer's disease, other dementias) ii. Malignant tumors (e.g., glioblastoma multiforme) iii. Brain injury (e.g. stroke, aneurysm, forcible trauma) iv. Chronic mental disorders (e.g., schizophrenia) v. Mood disorders (e.g., bipolar disorder, depression, PTSD) c. Treatment of brain disorders, i. Motor skills training (e.g. rehabilitation, sports) ii. Behavioral correction (e.g., drug addiction, rehabilitation) d. Neural reprogramming.

[0057] Detector 3 illustrates a further example of a therapy device 300. The therapy device 300 includes a frame 303 and a plurality of emitters 304 supported by the frame 303. The plurality of emitters 304 are configured to deliver at least one radiation modality (represented by beam 305) to a volume 307 within the head of a wearer of the therapy device. The therapy device 300 may also include one or more second and / or third emitters configured to deliver radiation of a second and / or third modality to the volume 307 within the head.

[0058] The treatment device 300 further includes a detector 350. The detector 350 is configured to detect at least one modality of signals emanating from within the wearer's head. The signals may emanate from a volume 307 irradiated by the multiple emitters 305 or may emanate from different volumes. The signals may correspond to the activation and destruction of drugs or liposomes from within the volume 307. The modality of the signal may be independent of the modality (or modalities) of radiation used to activate the drug. The detector 350 may be an ultrasound detector and the signals may be ultrasound signals.

[0059] By detecting signals associated with drug or liposome activation, drug release due to drug activation within the target volume 307 can be monitored in real time. This capability greatly enhances the utility of the treatment device 300 by providing real time feedback control options and a level of precision and participant safety that would otherwise require significant trial and error and experimentation with each participant.

[0060] For example, some configurations of the treatment device 300 may be capable of operating remotely or automatically. In these configurations, the detector 350 may be used as part of a control system to measure the progress of a given treatment and provide appropriate feedback to the emitter 305 (and / or other emitters, if present). For example, the dose of drug introduced into the volume 307 via an activated agent may be inferred or measured by the detector 350 and used to control a characteristic or operation of the emitter, such as: Enable or disable one or more emitters, Determine which emitters of a given modality should be used (in other words, enable one or more emitters based on the modality of the radiation); Automatically turning off one or more emitters when a sufficient dose has been administered; Adjusting the power, frequency, or other operating characteristics of one or more emitters; Adjusting the position and / or orientation of one or more emitters relative to the target volume and / or the frame of the treatment device.

[0061] The data acquired by detector 350 may also be recorded for later analysis.

[0062] The treatment device may include a number of such detectors 350. For example, the number of detectors 350 may be less than 10, 20, 50, 100, 300. The detectors 350 may be arranged in an array. The array may be sparse or dense. The exact geometry of the array will typically depend on the application of the treatment device, such as the location of the target volume 307 within the head and the number of emitters 305 included.

[0063] In some examples, the detector 350 may also be integrated with the emitter 305. For example, an ultrasound detector may be integrated with the ultrasound emitter. The therapy device 300 may include a combination of an emitter 305, a detector integrated with the emitter, and a dedicated detector 350.

[0064] The plurality of emitters 304 and / or the second emitter and / or the third emitter may be substantially as disclosed in connection with Figures 1 and 2. For example, the treatment device 300 may include: Ultrasonic emitters, Electromagnetic emitters, Magnetic field emitters, Combination of ultrasonic and electromagnetic emitters, Combination of ultrasonic and magnetic field emitters, Combination of electromagnetic and magnetic field emitters, A combination of ultrasonic, electromagnetic and magnetic field emitters.

[0065] Any or all of the emitter 304 and / or the second emitter and / or the third emitter may be tunable as described below.

[0066] Alternative detectors 350 may also be used in the treatment device 300. Examples of detectors 350 include ultrasound detectors, piezoelectric detectors, photon detectors, radio frequency radiation detectors, and / or magnetic detectors. Different detectors 350 may also be combined within a single treatment device 300.

[0067] In some examples, the therapeutic device includes acoustic and / or electromagnetic and / or magnetic emitters arranged as an array of adjustable emitters in a head-mounted frame, with each emitter individually delivering radiation to a designated volume within the skull, and by adjusting the parameters of the delivered radiation provided by the array of adjustable emitters, the combination of radiation at the intersections and intersections of the irradiated volumes provides effective single or mixed modality focused radiation to image the brain, damage portions of the brain, damage malignant tissue in the brain, activate neurons in the brain, repair brain damage, increase the permeability of the BBB for delivery of substances to the brain, and activate radiation responsive drugs to specific regions of the brain.

[0068] In some examples, the therapeutic device may include a head-wearable device incorporating an array of adjustable emitters that effectively delivers acoustic and / or electromagnetic and / or magnetic radiation to one or more volumes within the skull, and adjustment means for altering at least one parameter of the delivered radiation provided by the array of adjustable emitters.

[0069] In some examples, the treatment may include a head-wearable device incorporating an array of adjustable emitters that effectively deliver acoustic and / or electromagnetic and / or magnetic radiation to one or more volumes within the cranial cavity, an array of adjustable signal detectors that detect acoustic and / or electromagnetic and / or magnetic signals from the one or more volumes within the cranial cavity, and adjustment means for altering at least one parameter of the delivered radiation provided by the array of adjustable emitters.

[0070] In some examples, a method of delivering acoustic and / or electromagnetic and / or magnetic radiation to one or more designated volumes within the skull includes providing a head-wearable device incorporating an array of emitters configured to emit acoustic and / or electromagnetic and / or magnetic radiation, and adjusting the array of emitters to a defined shape and / or orientation and / or intensity to modify at least one parameter of the radiation and focus the effective radiation at the designated volumes within the skull.

[0071] In some examples, a method of manufacturing a therapeutic device includes: a. determining a three-dimensional topology of a head; b. determining the modality, number, and orientation of emitters required to deliver effective radiation to a specified volume within the skull; and c. manufacturing a head-mounted frame that conforms to the topology of the head and positions the emitters to deliver effective radiation to a designated volume within the skull, and optionally positions the signal detectors to effectively detect signals emanating from within the skull.

[0072] In some use cases of the treatment device, control of the adjustment of the delivered radiation may be performed based on one or more parameters selected from the group including emitter modality, number of emitters, emitter placement, emitter orientation, radiation modality, radiation orientation, radiation intensity, radiation power, radiation amplitude, radiation phase, radiation timing, and / or radiation frequency.

[0073] Adjustable Therapy Device Some therapeutic devices include emitters that are fixed in a static position relative to a frame of the therapeutic device. Alternatively or additionally, the therapeutic device may include adjustable emitters, which allows the therapeutic device emitters to target different areas and volumes within the wearer's head, thereby increasing the versatility of the therapeutic device.

[0074] 4 illustrates an example of a treatment device 400. The treatment device 400 includes a frame 403 configured to be worn on a head. The frame 403 supports a number of emitters 404 configured to deliver at least one radiation modality to a volume 407 within the head of the wearer 101. The treatment device 400 is configured to allow an orientation and / or position of the at least one emitter 404 relative to the frame 403 to be adjustable. The multiple emitters 404 are configured to deliver radiation to a common volume 407. The multiple emitters 404 can be configured to activate liposomes within the volume 407.

[0075] In this particular example, the frame 403 includes one or more rails or guides 460. The one or more emitters 404 may be secured to the rails or guides 460 at different positions on the frame 403, thereby allowing the position of the one or more emitters 404 relative to the head of the wearer 101 to be adjusted.

[0076] For example, one or more emitters 404 may be removably or permanently fixed to a carriage 465 that can slide along a rail or guide 460. The carriage 465 may be fixed at any position on the rail or guide 460 to set the position of the associated emitter 404. Some rails 460 may allow the carriage 465 to be fixed at any position along the rail 460, while other rails 460 may allow the carriage 465 to be fixed at one or more discrete positions. The carriage 465 may include a servo motor 468 that drives the carriage 465 along the rail 460 and sets its position. A stepper motor or the like may be used instead of the servo motor 468. Additionally or alternatively, a piezoelectric element 470 may be used to fine-tune the position of the carriage 465 on the rail 460. Additionally or alternatively, the carriage 465 may be manually adjusted around the rail 460.

[0077] The frame 403 may include a number of rails 460 and a carriage 465. The multiple rails 460 are substantially perpendicular to one another.

[0078] Some treatment devices 400 may include a combination of permanently fixed and adjustable emitters 404. The emitters 404 can pivot or rotate about one or more axes relative to the carriage 465, meaning that the angle and orientation of the emitters 404 can be adjusted relative to the head and volume 407 of the wearer 101. The emitters 404 can be manually pivoted about the carriage 465 (e.g., using a gimbal-like mechanism), actuated by a piezoelectric actuator, or the like, allowing the emitter emission direction to be adjusted very precisely.

[0079] The treatment device 400 includes one or more detectors as described herein, with particular reference to Figure 3. Additionally, the treatment device 400 may include any of the various types of emitters described herein, either alone or in combination. For example, the treatment device may include: Ultrasonic emitters, Electromagnetic emitters, Magnetic field emitters, Combination of ultrasonic and electromagnetic emitters, Combination of ultrasonic and magnetic field emitters, Combination of electromagnetic and magnetic field emitters, A combination of ultrasonic, electromagnetic and magnetic field emitters.

[0080] 5 illustrates a further example of an adjustable treatment device 500. The treatment device 500 includes a frame 503 including a plurality of openings 520 spaced about the frame 503 and configured to receive one or more emitters 504. The number of emitters 504 incorporated into the frame 503 and the initial location of the emitters relative to the frame 503 is determined during assembly or construction of the treatment device 500. The emitters 504 are preferably removable from the openings 520 in the frame 503 so that the number and / or location of the emitters 504 can be changed after initial assembly of the treatment device 500. Each emitter 504 is preferably pivotable about one or more axes within its opening so that the direction of emission can be adjusted.

[0081] The treatment device 500 may include one or more detectors as described herein, with particular reference to Figure 3. Additionally, the treatment device 500 may include any of the various types of emitters described herein, either alone or in combination. For example, the treatment device may include: Ultrasonic emitters, Electromagnetic emitters, Magnetic field emitters, Combination of ultrasonic and electromagnetic emitters, Combination of ultrasonic and magnetic field emitters, Combination of electromagnetic and magnetic field emitters, A combination of ultrasonic, electromagnetic and magnetic field emitters.

[0082] Manufacturing of medical devices The required number, modalities, and location / orientation of emitters of a given treatment device may vary depending on the application of the treatment device. For example, two different participants may require radiation of different modalities at two different volumes in their respective heads. Similarly, different head or skull shapes from person to person may affect the required configuration of the treatment device frame and / or emitters. For example, the diffraction and reflection of ultrasound radiation within the head may be affected by the shape of the skull and the distribution of various materials (e.g., bone, fat, and other tissues) within the head. It may therefore be advantageous to create a treatment device customized for use with a given head and specific application.

[0083] 6 shows an example of a method 600 for manufacturing a customized therapeutic device. First, the wearer's head is imaged at 610 to determine the three-dimensional topology of the head. A variety of imaging techniques can be used, including measurements, imaging, scanning, computed tomography (CT) scans, x-rays, magnetic resonance imaging (MRI), optical scans, magnetoencephalography (MEG), and / or positron emission tomography (PET) scans, alone or in combination, with or without contrast agents.

[0084] Next, at 620, at least one designated volume to be irradiated by the multiple emitters is identified from the three-dimensional topology of the head. Multiple volumes can be identified depending on the required application of the treatment device. Next, at 630, a desired orientation of the at least one emitter relative to the at least one designated volume is determined based on the designated volumes. At 640, the number of emitters required, the modality of the emitters, and / or the required position of the emitters relative to the at least one designated volume can also be determined as needed. Finite element modeling can be used to determine the placement and configuration of the emitters. The emitters can be positioned to deliver radiation to a common volume identified in the head using imaging of the head as described above. The emitters can be further positioned such that the common volume receives a threshold dose (e.g., to activate a drug or liposome), while the off-axis volumes receive a sub-threshold dose. At 650, the number and location and / or orientation of the detectors required or desired can also be determined as needed.

[0085] Once the desired orientation of the at least one emitter relative to the designated volume is determined at 630, then a customized frame configured to be worn on a head is manufactured at 660. The customized frame is configured to support the at least one emitter such that, upon wearing the customized frame on the head, the at least one emitter is positioned in a desired orientation relative to the at least one designated volume within the head.

[0086] In some examples, the customized frame can be manufactured using 3D printing or other additive manufacturing techniques. This allows for relatively rapid production of precision frames that are highly customized and yet can be produced at relatively low cost. Other forms of manufacturing are possible, such as precision subtractive manufacturing. The customized frame can be a skeletonized exoskull cap designed to place the required emitter-detector in a cradled orientation.

[0087] Scaling of the three-dimensional model and reprinting of the frames can accommodate changes in head size and retarget to other specific volumes within the skull. For example, a given participant may require multiple treatments at different treatment sites (e.g., due to multiple lesions in a treatment site) or at different times (e.g., undergoing a first radiation modality, then later a second radiation modality). A series of customized frames can be manufactured for that particular participant, with each individual frame configured for treatment at a particular site and / or time.

[0088] For example, a first customized frame can be configured to support one or more emitters in an orientation that targets a first treatment site. A second customized frame can be configured to support one or more emitters in an orientation that targets a second treatment site. The participant can then be treated at a first location (site) using the first customized frame, and then at a second location (site) using the second customized frame. Both the first and second customized frames are customized for the participant (e.g., can be configured to match the outer contours of the participant's head), but each individual frame is configured for the participant's particular treatment.

[0089] The location and orientation of the emitters relative to the customized frame, as well as the shape of the customized frame, can take into account the configuration of the wearer's head as well as the overall shape of the wearer's head.

[0090] For example, the propagation of ultrasound radiation through a wearer's head is subject to diffraction and reflection at interfaces of various types of tissue, such as muscle and bone. These interfaces may be numerous and of complex shapes that vary from head to head. Thus, accurate placement of an ultrasound emitter at the proper location and orientation relative to a target volume may require knowledge of the external contours of the wearer's head (i.e., scalp) as well as the internal configuration of the head.

[0091] Finite element modeling can be used to model how ultrasound radiation propagates through a wearer's head. The position and orientation of the ultrasound emitter can then be determined such that when the ultrasound emitter is in a desired position and orientation, the ultrasound radiation propagates and irradiates at least one identified volume with desired characteristics.

[0092] With particular reference to FIG. 3, the manufactured therapeutic device may include one or more detectors as described herein. Additionally, the manufactured therapeutic device may include any of the various emitters described herein, alone or in combination. Any or all of these emitters may be tunable as described herein. The manufactured therapeutic device may include: Ultrasonic emitters, Electromagnetic emitters, Magnetic field emitters, Combination of ultrasonic and electromagnetic emitters, Combination of ultrasonic and magnetic field emitters, Combination of electromagnetic and magnetic field emitters, A combination of ultrasonic, electromagnetic and magnetic field emitters.

[0093] Supporting Experiments To verify the headset's illumination of specific volumes within the skull, Applicants performed the following experiment.

[0094] Acoustic mapping of the emitter-detector ultrasound beam profile (individually and in sparse arrays), anatomically realistic 3D model heads, and cadaveric heads were used. High-resolution CT scans of the cadaveric heads were performed to establish anatomical compensation and custom positioning of the treatment device for ultrasound emission and detection measurements. In some cases, this scan was performed immediately prior to tissue fixation (necessary for long-term storage of cadavers) to allow comparison of radiation received with and without injection of acoustically sensitive liposomes into the cerebral vasculature. After stimulation, CT scans and dissections were performed. The brain was removed intact (craniotomy) and tissue-specific ultrasound hydrophone probes were inserted into each hemisphere within the striatal volume. The brain was placed back into the cranial vault, the skull was repaired, and the headset was reinstalled. Ultrasound radiation measured by the hydrophone in the dissected tissue was used to validate and refine the model predictions.

[0095] The skull was studied using a HIFU 256 channel Verasonics system that included a 3D scanning tank system to accurately determine the acoustic pressure magnitude and profile and to develop and validate the phase steering method.

[0096] We used liposomes containing dopamine agonists in sheep (Parkinson's disease model) injured with neurotoxins. Sheep preparation included i) CT head scan to determine emitter coordinates, ii) lesion surgery of the substantia nigra (injecting asymmetric amounts of toxin on both sides to promote asymmetric rotation and improve welfare) and recovery, iii) systemic DA challenge (apomorphine, dihydroxidine, ropinirole) to confirm injury and sensitivity, iv) placement of emitters on the animals, v) intravenous cannulation, and vi) behavioral assessment. At the end of the experiment, brains were harvested and catecholamine concentrations (dopamine, homovanillic acid, and dihydroxyphenylacetic acid) were measured by high performance liquid chromatography and cell loss in each substantia nigra was measured by immunohistochemistry. After bilateral injury, all sheep appeared to be slower moving, but were otherwise able to move and graze. We also showed that sheep could spontaneously turn when dopamine depletion was asymmetric.

[0097] Using liposomes containing dopamine agonists in injured sheep, we can selectively enhance the function of one striatum at a time to reverse asymmetric turning. This allows us to demonstrate the precise control of the system over separate (but functionally similar) brain regions. This provides an internal control (lesioned vs. non-lesioned) to compare to unoperated animals where liposomes containing dopamine antagonists are administered to effectively turn off the target region. Sheep preparation includes i) CT scan of the head to determine transducer coordinates, ii) lesion surgery of the substantia nigra in the operated animals (injecting asymmetric amounts of toxin on both sides to promote asymmetric turning and improve welfare) and recovery, iii) placement of emitters on the animals, iv) intravenous cannulation, and v) behavioral assessment. These experiments are demonstrated with pre-testing of rats to project ultrasound radiation to one side of the brain to confirm asymmetric turning.

[0098] Behavioral assessments in the paddock (including ultrasound detection recording) involved sheep being fitted with a harness carrying the emitter-controller-recorder electronics and GPS telemetry. Experimental sessions lasted 3-4 hours and involved applying ultrasound with or without circulating neuromodulator-loaded liposomes. All gross movements were recorded using satellite video and behavior was measured relative to control peers. There was asymmetric rotation, indicating that the head-mounted emitter applied sufficient acoustic pressure to a specific intracranial volume to achieve threshold activation of the acoustically sensitive liposomes.

[0099] Using high-resolution MRI scans, we verified the projection of the ultrasound signal by the headset by applying ultrasound and injecting enough microbubbles to open the BBB in the presence of the MRI contrast agent gadolinium. After ultrasound was applied, the headset was removed and the head was scanned to determine the extent and location of contrast agent extravasation.

[0100] Real-time drug release was monitored by detecting liposome-induced ultrasound radiation emanating from the focal region.

[0101] A mixed modality to trigger drug release from acoustically sensitized liposomes combines ultrasound and near-infrared (NIR) radiation, providing the added capability of enhancing noninvasive drug release at subthreshold acoustic pressures. A mixed-modality drug release paradigm combining monochromatic infrared radiation and ultrasonic pressure demonstrated that by incorporating NIR sensitizing functionality into ultrasound-sensitive liposomes (e.g., by incorporating the dye IR780 into the liposome bilayer), NIR irradiation and ultrasound, either individually or simultaneously, could trigger drug destruction and release.

[0102] Ultrasonic emitter Therapeutic devices may use ultrasound emitters that do not require surgical implantation. These devices may deliver ultrasound radiation to a volume within the wearer's head (e.g., a portion of the brain) via the wearer's scalp and scalp / skull interface. Applicant has discovered that the scalp-skull-brain pathway of the head may have poor acoustic transmission characteristics for delivering ultrasound radiation to the brain for neurotherapy. Acoustic losses may occur, particularly at the interface between the wearer's scalp and skull. Conventional ultrasound emitters that are not designed to minimize these losses may be inappropriate or less desirable for use in wearable therapeutic devices.

[0103] FIG. 7 illustrates an example of a treatment device 700 that includes an adjustable frame 703 (only partially shown) that supports three ultrasound emitters 704. The ultrasound emitters 704 are configured to deliver ultrasound radiation to a volume within the wearer's head through the wearer's scalp / skull interface. Losses at the scalp / skull interface can be minimized if the ultrasound emitters are configured to establish a resonator with the scalp / skull interface to match the impedance of the interface. The operating frequency of the emitters can be selected, at least in part, to improve the transmission of ultrasound radiation through the wearer's skull. Other design factors (such as the type of treatment required by the wearer) may also at least in part determine the operating frequency of the ultrasound emitters.

[0104] The ultrasound emitter 704 is small and typically sized for use in a convenient head-mounted therapy device. The ultrasound emitter 704 shown in FIG. 7 has a diameter of 35 millimeters (mm), a thickness of 10 mm, and a weight of 45 grams. The electronic circuitry used to control the therapy device 700 (not shown) can also have a form factor of portable size (e.g., a footprint of about 8 centimeters (cm) by 5 cm or less). The control of the therapy device 700 can be completely defined by hardware embedding of the control circuitry, so no microprocessor or computer is required. Monitoring functions can be built into the control circuitry so that the therapy device 700 can be configured to be fail-safe.

[0105] The ultrasonic emitters were characterized by measuring the emitted ultrasonic radiation using a 3D scanning tank system and a hydrophone. Figure 8 shows the signal 801 measured by the hydrophone in the time domain. The hydrophone signal is represented in volts on the y-axis 805 against time (in microseconds) on axis 810.

[0106] Also shown in Figure 8 is the hydrophone signal 802 in the frequency domain, represented in dB on the y-axis 815 versus frequency in KHz on the x-axis 820. The output of the ultrasonic emitter has a fundamental frequency of approximately 520 KHz, as shown by peak 830. The second, third and fifth harmonics are shown at 840, 850 and 870, respectively. The amplitudes of these peaks are approximately -45 dB relative to the amplitude of the fundamental frequency. The amplitude of the fourth harmonic 860 does not appear to be significantly above the noise floor of the signal in the frequency domain.

[0107] Figures 9 and 10 are contour plots showing the sound pressure level at various positions relative to one of the ultrasound emitters. Figure 9 is a horizontal plot showing the measured sound pressure level in the xy plane at a fixed depth (i.e., z coordinate). The measured sound pressure (usually designated 910) is approximately symmetric about a radial axis 920 (either "inside" or "outside" the page from the perspective of Figure 9).

[0108] 10 is an axial plot showing the sound pressure level of an xz plate at a fixed y coordinate. The measured sound pressure 1010 is approximately symmetric about the radial axis 1020.

[0109] The ability of the ultrasound emitters to transmit ultrasound radiation through the scalp / skull interface was characterized using the True Phantom Solutions phantom head, which has a structure that mimics the average human head (including the scalp and skull) and is made of materials that mimic the acoustic properties of the average human head.

[0110] FIG. 11 illustrates the desired orientation of multiple emitters relative to a phantom head 1110. The phantom head 1110 was imaged to determine its three-dimensional topology. A designated volume to be treated (designated 1107) was identified from the three-dimensional topology of the phantom head 1110. Modeling was used to determine the desired orientation of five ultrasound emitters 1104 such that the ultrasound emitters 1104 irradiate the volume 1107. The radiation axes 1105 of each ultrasound emitter 1104 are approximately orthogonal to one another in this desired orientation and intersect at a common volume 1107 to be treated. The ultrasound radiation must pass through the scalp and scalp / skull interface of the phantom head 1110 to reach the volume 1107.

[0111] The ultrasound emitters were purposefully selected in this experiment to characterize their ability to transmit ultrasound radiation through the scalp / skull interface. In other examples, the modality of the emitters can be determined at least in part based on the imaged topology and identified volume 1107 of the phantom head 1110. Similarly, while five ultrasound emitters 1104 were selected in this experiment, the number of emitters can also be determined at least in part depending on the imaged topology of the phantom head 1110, the nature of the volume 1107 (including, for example, the size, shape, location, and / or contents of the volume 1107), and the nature of the treatment required.

[0112] The imaged topology of the phantom head 1110 was then used to fabricate a customized frame configured to support the emitter 1104 in a desired orientation around the phantom head 1110. Figures 12 and 13 show the treatment device mounted on the phantom head 1110. The ultrasound emitter 1104 is in contact with the outer scalp of the phantom head 1110 and is positioned in a desired orientation with respect to the volume 1107 within the head (as shown in Figure 11). In this case, the customized frame surrounds the phantom head 1110. The customized frame supporting the emitter 1104 can be 3D printed or constructed using other additive manufacturing techniques, or constructed using any of the techniques described herein using the imaged topology. A series of customized frames can also be constructed for the phantom head 1110, for example, if other volumes within the head need to be treated, if the same volume 1107 needs to be treated from different orientations of the emitter (e.g., if the volume 1107 is particularly large), or if further treatment is required at a later stage. As described herein, the therapy device may also include detectors, emitters of various modalities, either alone or in combination, and / or one or more tunable emitters.

[0113] An ultrasound emitter 1104 was used to irradiate the volume 1107 and the sound pressure in the volume 1007 was measured to determine the transmission of ultrasound radiation through the scalp / skull interface. Losses at the scalp / skull interface were reduced by impedance matching due to reverberation at the scalp / skull interface. Experimental data suggests that refraction by the skull may affect the focal depth of each ultrasound emitter. Taking this into account, the required focal depth can be achieved. The acoustic signal loss caused by wave scattering by the porosity of the skull was significantly less than the signal loss due to wave scattering in the sheep skull.

[0114] advantage Among the advantages already discussed above, a therapeutic device is disclosed herein that can deliver ultrasonic pressure and / or photon illumination and / or radio frequency radiation and / or magnetic field to a specific volume within the skull with a single or mixed emission modality. The array of emitters allows sub-threshold radiation to be delivered from individual emitters to a volume within the skull only if the intersecting radiation from the multiple emitters is above threshold, thus minimizing non-specific effects. The exemplary therapeutic device does not require surgical installation, can deliver continuous or semi-continuous or on-demand acoustic pressure and / or photon illumination and / or radio frequency radiation and / or magnetic field to a specific volume within the skull, can be conveniently reconfigured to another volume within the skull, can be conveniently maintained, and is relatively inexpensive to manufacture, making it widely available.

[0115] Some examples of therapy devices can be used to provide telehealth in communities far from resources or during times when infectious diseases (such as Covid-19) limit personal mobility. Some examples of therapy devices can also be used in communities where surgical interventions on the head are culturally challenging. The use of detectors that allow for automated control of the therapy device also allows for therapy in non-traditional settings. For example, in some cases the therapy device frame can be made into a non-hazardous piece of clothing or accessory (such as glasses) and therapy can be delivered at a convenient time, such as on a bus or at home. In contrast, traditional therapy may need to be delivered in a specialized facility under the direct supervision of a medical professional.

[0116] The use of therapeutic devices can overcome some of the drawbacks present in conventional precision brain surgery to damage parts of the brain, repair brain damage, remove malignant tissue, or insert electrodes to stimulate the brain. These conventional surgical procedures are highly invasive and involve many risks associated with craniotomy, which surgically removes a portion of the skull to access the brain. Surgical risks include, for example, blood loss, tissue damage, infection, and adverse reactions to anesthetic drugs.

[0117] While the present invention has been described by way of illustration of embodiments thereof, and the embodiments have been described in detail, it is not the intention of the applicants to restrict or in any way limit the scope of the appended claims to such details. Additional advantages and modifications will readily occur to those skilled in the art. Thus, the invention in its broader aspects is not limited to the specific details, representative apparatus and methods, and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of the applicants' general inventive concept.

Claims

1. A therapeutic device configured to be worn on the head, the therapeutic device comprising: a frame configured to be worn on the head; a plurality of emitters supported by the frame; the plurality of emitters are configured to deliver ultrasound radiation to a volume within the head; the plurality of emitters are configured to activate a drug, release a drug, activate microbubbles, or perform neuromodulation within the volume illuminated by the emitters; treatment equipment.

2. The treatment device of claim 1 , further comprising a plurality of second emitters configured to deliver a magnetic radiation modality to the volume within the head.

3. The treatment device of claim 1 , further comprising a plurality of third emitters configured to deliver a modality of electromagnetic radiation to the volume within the head.

4. 10. The therapeutic device of claim 1, further comprising at least one detector selected from an ultrasound detector, a magnetic detector, or an electromagnetic detector configured to detect at least one modality of signals emanating from the head.

5. The treatment device of claim 4 , wherein the at least one detector is integrated with the emitter.

6. The therapeutic device of claim 4 , wherein the detector is configured to monitor release of a drug within the volume of the head.

7. 10. The treatment device of claim 6, further comprising a control system configured to measure the progress of a given treatment.

8. The treatment device of claim 7 , wherein the control system provides feedback to at least one emitter.

9. The treatment device of claim 8 , wherein the feedback is used to enable or disable one or more emitters.

10. A therapeutic device as described in claim 1, wherein one or more of the emitters are enabled or disabled based on the modality of the radiation.

11. 10. The therapy device of claim 8, wherein the feedback is used to automatically turn off one or more emitters when a sufficient radiation dose has been administered.

12. 9. The treatment device of claim 8, wherein the feedback is used to adjust the position and / or orientation of one or more emitters relative to the volume and / or frame of the treatment device.

13. The treatment device of claim 1 , wherein the orientation and / or position of at least one emitter is adjustable relative to the frame.

14. A treatment device as described in any one of claims 1 to 13, wherein the treatment device is a portable device.

15. A treatment device as described in claim 14, wherein the treatment device is not connected by a cable.

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