Structures and methods for modifying ultrasound therapy - Patents.com

Abstract

A structure and method for ultrasound treatment of neurological and psychological disorders using energy levels that do not cause heating or cavitation. The structure includes an outer frame comprising a first material and a disk positioned inside the outer frame. The disk comprises a second material that is compositionally different from the first material and has a higher acoustic attenuation rate of ultrasonic energy than the first material. In one embodiment, the second material is an open cell foam. In one embodiment, the second material is a closed cell foam.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Application No. 63 / 177,084, filed April 20, 2021, which is incorporated by reference in its entirety.

[0002] The present disclosure is directed to ultrasound, and more particularly to structures and methods for ultrasound treatment of neurological and psychological disorders using energy levels that do not cause heating or cavitation. [Background technology]

[0003] Ultrasonic or ultrasound therapy can be used to treat a variety of disorders, such as neurological and psychological disorders. During treatment, a level of ultrasound energy should be delivered to specific areas in the brain, such as, but not limited to, the amygdala, hippocampus, entorhinal cortex, ventral striatum, and thalamus regions, among others. The ultrasound energy is delivered through the bones of the skull and focused onto the desired area within the skull.

[0004] When conducting the study, the patient / subject should be unaware of the treatment condition, so that the true effect of the treatment can be evaluated independently of any conscious actions of the patient. This is called "blinding" of the subject. This is also known as "placebo" or "sham" treatment, and is employed to determine the effect of ultrasound treatment when the patient can affect the results by their actions, inactions, or reactions.

[0005] Some neurological conditions, such as anxiety, may be influenced by factors other than ultrasound therapy. For example, the ultrasound transducer itself may generate audible sounds while delivering ultrasound for therapy. Such audible sounds may be perceived by the patient and may increase, decrease, or change the anxiety of the patient. The approach to not administering ultrasound therapy to the placebo test group was to apply the transducer to the subject's head, but not activate the transducer, so that there is no actual ultrasound therapy.

[0006] The approach of not administering ultrasound to patients in the placebo group fails to adequately address the problem due to the mechanics of the transducer itself. When turned on to administer ultrasound, the transducer produces an audible "click" or "buzz" sound that can be heard by the patient. When the transducer is turned off to not administer ultrasound, the "click" sound is not made by the transducer and therefore is not heard by the patient. This creates a distinguishable difference between the actual treatment and the placebo treatment that can be discerned by the patient and by the operator administering the treatment.

[0007] Another approach to inhibiting ultrasound therapy is to use a non-functional ultrasound transducer, but this presents similar problems to the audible "click" or "buzz" sound as when the transducer is not excited.

[0008] Another approach to inhibiting ultrasound therapy is to not properly acoustically couple the ultrasound transducer to the subject's head, either by leaving a gap between the front of the transducer and the subject's skull, or by mounting the transducer in an inverted position (facing away from the subject's skull). In either case, the difference between the actual treatment and the placebo treatment may be enough for the subject to perceive that the treatment conditions are different. The operator who must place the transducer certainly perceives the difference.

[0009] During single- or double-blind studies, approaches to blinding the patient and / or the operator have not been proven adequate and involve electrical approaches (such as not exciting the transducer) or mechanical approaches (such as reorienting the transducer to face away from the patient). Both approaches can be undesirably discriminated by either the patient or the operator, or both.

[0010] As a further example of a blinded procedure, there may be a desire for a third condition beyond the full treatment and the sham or placebo treatment. Such a third condition may involve modification of the ultrasound beam characteristics, such as a reduction or modification (though not a complete elimination) of exposure, which may involve a transducer transmission surface geometry smaller than that used for the full treatment, or an annular or otherwise geometrically limited or modified transmission surface geometry, which would lead to a different ultrasound beam pattern in the patient. Current single element transducer technology does not allow for such modifications, except by substituting a modified transducer. This substitution approach would not be discernible to the patient, but the operator would be aware of the substitution. This would also involve additional costs for the production of additional transducers with modified geometry.

[0011] Improved structures and methods for inhibiting, enabling, or modifying ultrasound therapy are needed. Summary of the Invention [Means for solving the problem]

[0012] In one embodiment of the invention, a structure includes an outer frame comprising a first material and a disk positioned inside the outer frame, the disk comprising a second material that is compositionally different from the first material and has a higher acoustic attenuation of ultrasonic energy than the first material.

[0013] In one embodiment of the invention, the method includes, in a first stage of a molding process, introducing a first layer of a first material into a mold, inserting a disk into the mold, and in a second stage of the molding process, introducing a second layer of the first material into the mold. The disk is surrounded by a gap between the disk and the mold, and the second layer of the first material fills the gap and provides a physical connection with the first layer. The method further includes curing the first and second layers of the first material.

[0014] In one embodiment of the invention, the method of treatment includes transmitting ultrasound energy from an ultrasound transducer through a first pad to provide a real exposure, and further including transmitting ultrasound energy from the ultrasound transducer through a second pad that significantly attenuates the transmission of the ultrasound energy to provide a placebo exposure. [Brief description of the drawings]

[0015] Embodiments will be readily understood from the following detailed description, taken in conjunction with the accompanying drawings and the appended claims, and are illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings.

[0016] [Figure 1A] FIG. 1A illustrates generally an ultrasound treatment device with a transducer holder holding an ultrasound transducer at a first angle (eg, a 0 degree angle) and with a corresponding gel pad, according to various embodiments.

[0017] [Figure 1B] FIG. 1B illustrates the ultrasound treatment device of FIG. 1A, showing the path of an ultrasound beam from a transducer through a gel pad, according to various embodiments.

[0018] [Figure 2A]FIG. 2A illustrates an ultrasound treatment device with a transducer holder that holds an ultrasound transducer at a second angle (eg, a 5 degree angle) and with a corresponding gel pad, according to various embodiments.

[0019] [Figure 2B] FIG. 2B illustrates the ultrasound treatment device of FIG. 2A, showing the path of the ultrasound beam from the transducer through the gel pad, according to various embodiments.

[0020] [Diagram 3] FIG. 3 is a schematic illustration of a top view of a non-conductive gel pad that may be coupled to a transducer during treatment.

[0021] [Figure 4] 4A and 4B are schematic illustrations of side cross-sectional views of non-conductive gel pads (0 degrees and 5 degrees) that may be coupled to a transducer during treatment.

[0022] [Diagram 5] FIG. 5 is a schematic illustration of a top view of a transmissive gel pad that may be coupled to a transducer during treatment.

[0023] [Figure 6] 6A and 6B are schematic illustrations of side cross-sectional views of transmissive gel pads (0 degrees and 5 degrees) that can be coupled to a transducer during treatment.

[0024] [Figure 7] 7A and 7B are schematic illustrations of a top view of a modified transmissive gel pad that can be coupled to a transducer during treatment.

[0025] [Figure 8] FIG. 8 is a schematic illustration of a side cross-sectional view of a modified transmissive gel pad. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] Detailed Description FIG. 1A is a schematic depiction of an ultrasound device 50 as applied to a patient 60. A transducer holder 10 may be affixed to the skull of the patient 60 using an elastic strap 15. A transducer 30 is clipped into the holder 10. A gel pad 20, a 0 degree pad, is coupled to the transducer 30 and allows transmission of ultrasound to the patient since ultrasound cannot travel through air. The transmission plane 40 is where the ultrasound will be focused. The transducer 30 is off and not emitting any pulses.

[0027] In one embodiment, the transducer 30 may be connected to a system such as provided in "Design, development and operation of a Low Intensity Focused Ultrasound Pulsations (LIFUP) system for clinical use" by Schafer, Spivak, Korb, and Bystritsky, IEEE Trans Ultrason. Ferroelectr. Freq Control 68(1):54-64 2021 DOI: 10.1109 / TUFFC.2020.3006781, and / or U.S. Patent Publication No. 2021 / 0361975, which are incorporated by reference in their entirety into this specification.

[0028] Figure 1B is a schematic illustration of ultrasound device 50 as described in Figure 1A, but with transducer 30 excited to the on state and emitting a pulse to form a beam 70 along a transmission plane 40 into the brain of patient 60. Gel pad 20 allows ultrasound waves to be transmitted to and pass through the brain of patient 60.

[0029] FIG. 2A is a schematic depiction of an ultrasound device 50 as applied to a patient 60. The transducer holder 10 may be affixed to the skull of the patient 60 using an elastic strap 15. The transducer 30 is clipped into the holder 10. A gel pad 22, a 5 degree pad, is coupled to the transducer 30 and allows for the transmission of ultrasound to the patient since ultrasound cannot travel through air. The transmission plane 40 is where the ultrasound will be focused. The transducer 30 is off and not emitting any pulses.

[0030] 2B is a schematic depiction of ultrasound device 50 as described in FIG. 2A, but with transducer 30 on and pulsing to form beam 70 along plane 40 within the brain of patient 60. Gel pad 22 changes the trajectory of beam 70 by 5 degrees. Gel pad 22 allows ultrasound waves to be transmitted to and pass through the brain of patient 60. Gel pads 20, 22 may be employed to provide the actual exposure or treatment.

[0031] Depending on the anatomical region in the brain to be treated with ultrasound, the angle of the transducer 30 (provided by the wedge angle of the gel pad) may be different, and the angle is not limited exclusively to 0 degrees or 5 degrees, but can range continuously from 0 degrees to at least 5 degrees. In an embodiment, the angle may range from 0 degrees to 5 degrees. The gel pad may be sufficiently flexible, compressible, and conformable to accommodate a range of transducer angles. For example, a transducer plane 40 providing an angle of 0 or 1 or 2 or 3 degrees would be accommodated by a gel pad 20 of 0 degrees, while a transducer angle 40 of 3 to 8 degrees would be accommodated by a gel pad 22 of 5 degrees. Also, gel pads may be produced with wedge angles other than only 0 and 5 degrees. Angles greater than 8 degrees may produce distortions in the ultrasound beam due to the acoustic properties of the skull.

[0032] 3 is a schematic depiction of a top view of a non-transmissive gel pad 23 that will be coupled to the transducer 30 described in the previous figure. A mating collar 80 allows the gel pad to mate with the face of the transducer 30. In an embodiment, the mating collar 80 may be made by additive manufacturing methods (3D printing) using fused deposition modeling (FDM) printed Ultem 9085 (or other suitable thermoplastics) or can be molded using, for example, DuPont Nylon 66 - Minlon 10B40 NC010 or polyetherimide 1000 (or other similar polymers). In an embodiment, the material 90 may be a skin-safe two-part silicone (Dragon Skin NV-10 from Smooth-On Inc, Macungie, PA) with little to no ultrasonic attenuation properties. The material 90 may be dyed white with a skin-safe silicone dye (Silc-Pig from Smooth-On Inc, Macungie, PA) to hide the internal contents of the pad. This material provides the required acoustic properties and mechanical stability and flexibility, although other similar materials could potentially be used. Acoustic requirements include, but are not limited to, low loss (less than 5%) and slight reflective bending of the beam due to sound speed difference (hence sound speed within 20% of tissue). Mechanically, the gel pad may conform to both the front of the transducer 30 and the surface of the skull, and must be compressible (e.g., Shore 30A) to fill the gap between the two. In use, a fluid ultrasound coupling material such as Aquasonic 100 (Parker Labs, New Jersey) may be placed between the transducer 30 and the gel pad, and between the gel pad and the skull to allow proper acoustic transmission.

[0033] The material 90 may be made in a process that is compatible with the inclusion of the foam disc 100. For example, the gel pad material 90 may limit processing temperatures (i.e., heating above 170° C., for example) during the molding process that may melt the foam disc material 100. The final gel pad material 90 should also be optically opaque, or alternatively, highly translucent, such that it is not visually evident whether the foam disc 100 is present in the final device, and visualization of the foam disc 100 is prevented. For example, a gel pad 20 made from a material that is completely transparent would allow easy identification of a gel pad containing a foam disc 100.

[0034] The foam disk 100 may be embedded in the material 90 during the multi-stage curing process to prevent any portions of the foam from floating to the surface of the material during curing. The foam disk 100 is made of a material with a different composition than the material 90 and with a higher acoustic attenuation of ultrasonic energy than the material 90. In an embodiment, the foam disk 100 may be made of an open cell material such as an open cell polyethylene foam cladding material (e.g., McMaster Carr (Elmhurst IL, PN 2007T41)). In an alternative embodiment, the foam disk 100 may be made of a closed cell material (e.g., Styrofoam). The open cell foam may provide better adhesion to the material 90 resulting in better cohesion in the final product. The closed cell foam may also tend to be harder and more brittle than thin open cell foams, which may affect mechanical performance and may make non-conductive pads more distinguishable from conductive pads. The thickness of the material 100 should be as thin as possible, e.g., 1 / 32 inch, since it should fit within the existing structure of the gel pad. Typically, the gel pad is designed to be as thin as possible, although if a thicker gel pad is designed for a conductive frame, this allows a thicker foam disk 100 to be used. Degassing during the assembly process may not be required when making a non-conductive pad, since any remaining air bubbles in the material after curing would add to the ultrasonic blocking effect of the pad.

[0035] 4A, 4B are schematic representations showing respective side cross-sectional views of a non-conductive 0 degree pad (23) and a 5 degree pad (24), respectively. The foam disk 100 is embedded within the material 90 during production, thus providing an outer frame surrounding the embedded foam disk 100. In some embodiments, the foam disk 100 may be embedded centrally in the middle of the material 90. In some embodiments, the thickness of the material 90 may be present within the gap between the foam disk 100 and the respective outer surface 23a, 24a of the pad 23, 24. That is, the foam disk 100 has an outer boundary or edge that is smaller than the inner extent of the mold, thus a gap exists between the foam disk 100 and the mold, centered on the outer edge of the foam disk 100. The gel pads 23, 24 may be employed to provide a placebo exposure or treatment.

[0036] FIG. 5 is a schematic depiction showing a top view of a transmissive gel pad 20 coupled to a transducer 30 as described in the previous figures. A mating ring 80 allows the gel pad 20 to align with the face of the transducer 30. The transducer 30 has an outer ridge on its face into which the mating ring 80 can fit. This aligns the gel pad 20 onto the face of the transducer 30. The size of the gel pad 20 should therefore match the transducer 30. The transducer 30 may have any diameter, but a range of clinically useful transducers, e.g., 20mm to 70mm, within 60mm, is typical. In use, a fluid ultrasound coupling material such as Aquasonic 100 (Parker Labs, New Jersey) may be applied to the surface of the gel pad 20 and the transducer 30, and the gel pad 20 tends to stay in place on the transducer 30, facilitating placement of the transducer 30 on the skull.

[0037] The face of the transducer 30 may be flat, concave, or convex. The illustration of the exemplary transducer 30 shown in the figures depicts a convex face. The gel pad 20, 23, or 25 may have a matching concave surface, so that there will be intimate physical contact between the gel pad 20, 23, or 25 and the face of the transducer 30. The opposing side of the gel pad 20, 23, or 25 may be planar and match the surface of the skull. However, that surface may be convex if it provides a better fit to the surface of the skull, depending on the region of the head where the transducer 30 will be used. For example, if the transducer 30 is to be placed on the top of the skull rather than the temporal area (which is generally flat), the gel pad 20, 23, or 25 may be shaped to match the curvature of the skull surface.

[0038] Although this embodiment is directed to the application of ultrasound to the skull, it is also suitable for ultrasound applications to any part of the body where experimental methods require similar blinding of the patient and / or operator, for example, in stimulation of the peripheral nervous system. In such cases, the gel pad 20 or 23 can be fitted to the surface of the skin over the area to be treated.

[0039] Although the transducer 30 and gel pads 20, 23, and 25 are shown with a circular geometry, other transducer designs can be used that may have, for example, an oval, rectangular, square, or other surface geometry. In those cases, the gel pads 20, 23, and 25 can be easily adapted by modifying the mold into which the material 90 is poured, and by modifying the foam disk 100 and mating ring 80.

[0040] The conductive pad should be devoid of any, or substantially any, attenuating components, and therefore no foam disks are embedded in. Any remaining air bubbles within material 90 will block ultrasonic transmission, so degassing may be required prior to the end of the pot life of material 90.

[0041] After mixing the silicone material with pigment part A and part B as described in the manufacturer's instructions, the mixture can be degassed for 3 minutes at -90 kPa and then introduced into the mold by pouring during the molding process, at which point it can be degassed again for 10 minutes at the same vacuum level. A small vacuum chamber (e.g. Carolina Supply Vacuum Chamber System #752951) is sufficient with a standard small vacuum pump.

[0042] 6A and 6B are schematic illustrations of side cross-sectional views of transmissive 0 degree (20) and 5 degree (22) pads, respectively. No foam disks are embedded within these pads, and the material 90 can be degassed to remove any air bubbles that may cause attenuation.

[0043] Referring again to Figures 3-4, the foam disc 100 may be centered within the gel pad 23 and may be of sufficient diameter to intercept the ultrasound beam 70. Depending on the geometry of the ultrasound beam 70, the foam disc 100 may not need to extend completely across the entire area of ​​the gel pad 23 as shown in the figures. However, the relative diameters of the foam disc 100 and gel pad 23 shown in the figures are for purposes of clarity of illustration only and are not to be construed as specific design features. After the bottom layer of material 90 is introduced (i.e., poured) into the form during the molding process, the foam disc 10 is placed into the form. Making the foam disc 100 the same diameter as the gel pad 23 would be believed to most completely block the ultrasound beam 70, but requires that there be an area (e.g., an annular area) around the periphery of the foam disc 100 (visible in FIGS. 3, 4A, and 4B) so that when the top layer of material 90 is introduced (i.e., poured) onto the foam disc 100, there is physical connectivity between the top and bottom layers. Otherwise, the gel pad 23 may lack sufficient structural integrity and may delaminate. Additionally, if the foam disc 100 is too wide, distinguishable features may appear on the outer surface of the gel pad 23, defeating the purpose of having visually and physically identical transmissive and non-transmissive gel pads.

[0044] 7A, 7B, 8 show an embodiment of a foam disk 105 that has been modified to have a central aperture 110 that allows ultrasonic energy to pass through it. This would have the effect of modifying the ultrasonic beam and effectively changing the diameter of the ultrasonic transducer. In this case, the focal depth of the transmitted ultrasonic energy 70 would not change, but the beam width at the focal point would increase. In an alternative embodiment, the modified foam disk 105 may lack the central aperture 110, but instead have a smaller diameter than the foam disk 100. In this case, the ultrasonic beam 70 would resemble that of an annular ultrasonic element, which would again have a similar focal length, but would be modified in its beam pattern. In an embodiment, the foam disk 105 may have a diameter that is less than 80% of the diameter of a pad that provides substantially complete attenuation and non-transmission. In an embodiment, the foam disk 105 may have a diameter that is less than 85% of the diameter of a pad that provides substantially complete attenuation and non-transmission. In some embodiments, the foam disc 105 may have a diameter that is less than 90% of the diameter of a pad that provides substantially complete attenuation and non-transmission. In some embodiments, the foam disc 105 may have a diameter that is less than 95% of the diameter of a pad that provides substantially complete attenuation and non-transmission. In some embodiments, the gel pad with the foam disc 100 may attenuate the ultrasound beam and create losses such that less than about 0.7% of the ultrasound energy is passed through, whereas the gel pad with the reduced diameter foam disc 105 may allow for high throughput, such as 3% or more of the ultrasound energy.

[0045] The openings 110 may be any shape that may be of interest other than a circular shape, such as an oval (when the overall transducer 30 has a circular transmission surface shape) or a rectangle (when the overall transducer 30 has a rectangular transmission surface shape), or some other non-circular shape such as a square, star, etc. The modified foam disc 105 may also be used in angled gel pads such as the one illustrated in FIG. 4B, i.e., element 24.

[0046] The disclosed embodiments allow the transducer 30 to be excited and pulsed while effectively blocking or modifying all or substantially all of the ultrasound energy 70 from entering the patient's brain to provide a different ultrasound exposure pattern within the brain. In certain embodiments, the gel pads 23, 24 may attenuate the ultrasound energy emitted from the transducer 30 to a transmissibility of less than 0.3% due to the positioning of the foam disc 100 within the transmission path. In certain embodiments, the gel pads 23, 24 may attenuate the ultrasound energy emitted from the transducer 30 to a transmissibility of 0.3% and 0.7%, or between -43 dB and -50 dB, due to the positioning of the foam disc 100 within the transmission path.

[0047] The disclosed embodiments allow for experiments in which operators are blinded to exposure conditions, particularly in those situations in which the objects being exposed (e.g., tissue samples, animals, cell cultures) may not necessarily need to be blinded.

[0048] In contrast, previous solutions do not contemplate the source of the ultrasound, i.e., the transducer 30, and do not generate anything that would block or modify the ultrasound energy 70.

[0049] The gel pads of various embodiments isolate non-ultrasonic (i.e., audible) effects from the combination of ultrasonic and non-ultrasonic effects. As a result, ultrasound can be selectively delivered into the patient without attenuating or altering the audible sound produced by the transducer. This can therefore isolate any patient's response to audible sound from their response to ultrasound treatment and provide a way to accurately describe the effects of ultrasound. Patients / subjects should be blinded as to whether ultrasound was actually delivered into their brain without affecting other possible cues such as sound, or whether the ultrasound was of different beam characteristics. Patient blinding may be utilized in studies where the effects of the presence or absence of ultrasound energy, or the effects of two or more ultrasound beam characteristics, are compared using the same patient or patient group. Study results may not be affected because the gel pads of various embodiments block or otherwise significantly limit the patient / subject from distinguishing between treatment conditions. Furthermore, when conducting such experiments, the gel pads of various embodiments may prevent the operator applying the ultrasound transducer from having an obvious clue as to the treatment state (i.e., transmission or non-transmission). This additional aspect is known as "double blinding," and thus the operator cannot provide subtle clues to the patient / subject as to which treatment state (presence or absence of ultrasound energy into the brain) is associated.

[0050] The gel pads of various embodiments can create the same test conditions for single-blind and double-blind studies for neuromodulation therapy or other ultrasound treatments, so that patients and the person administering the treatment (operator) cannot distinguish which patient groups are receiving ultrasound treatment and which are not.

[0051] Working Example A prototype transmissive pad and a prototype non-transmissive pad, substantially similar to the pads 20, 23 disclosed herein, were fabricated and tested in a water tank with a transducer and a standard hydrophone (underwater hydrophone) to measure the actual ultrasonic energy emitted from the transducer. The table below shows the difference in ultrasonic transmission between a transmissive pad and a non-transmissive pad. The table lists the amplitude of the waveform (in volts peak-to-peak (Vpp)) received by the hydrophone under each test condition relative to the amplitude when no pad is in place (reference condition). The tests were performed using a 60 mm diameter, 80 mm focal circular disk transducer operated at 650 kHz. [Table 1]

[0052] The results show negligible ultrasound attenuation using the transmissive pad, with a loss of approximately 40 dB for the non-transmissive pad indicating significant ultrasound attenuation.

[0053] In subsequent experiments, six sets of conductive and non-conductive pads substantially similar to the pads 22, 24 disclosed herein were fabricated and tested in a water tank with a transducer. The table below shows the relative loss of ultrasonic intensity due to the gel pads when placed in front of the transducer. [Table 2]

[0054] A test was performed to determine whether operators could distinguish the differences in the pads by visual inspection or informal physical manipulation. Operators experienced in the treatment of patients with ultrasound were asked to inspect and handle two gel pads, one each of the transmitting type (gel pad 20) and the non-transmitting type (gel pad 23). The operators were unable to distinguish between them by visual inspection or informal physical manipulation, as would be the clinical case.

[0055] A test was performed to determine if patients could distinguish the difference in pads based on use in a simple exposure experiment. Subjects with extensive experience in typical ultrasound treatments to the skull (as replicate subjects) were exposed to a typical ultrasound treatment regimen, once using a transmissive pad and once using a non-transmissive pad. The subjects were asked to discern the difference between the two. The subjects were unable to distinguish any difference, either sensory or audible, between the two types.

[0056] The embodiments of the present invention provide a method of single-blind and double-blind testing that would be indistinguishable to anyone not informed of the details of the study. For example, during clinical use, the two types of pads may be supplied with individual serial numbers. The serial number of each pad may be recorded as part of the test sequence. During all tests, the transducer will be on and emitting ultrasound energy, but the specific pad will either block (or substantially block) transmission, substantially modify transmission, or allow full transmission of ultrasound to the patient. No person aware of the specific type of pad, full transmission, modified, or non-transmission, may be part of the clinical situation and only after subsequent analysis of clinical exposure and clinical effects may reveal the type of pad used for any given test. This process is called "unblinding" and is used in double-blind studies, which are considered the highest level of clinical testing.

[0057] The modified pad 25 as shown in FIG. 7 also allows for the generation of different ultrasound energy deposition patterns, beam shapes, etc., depending on the geometry of the foam disc 105 and aperture 110. This allows for different exposure conditions without the need to generate different ultrasound transducers, which are much more expensive to construct than gel pads. The modified pad 25 may be used for experiments other than neuromodulation therapy, experiments without blinding, and for the generation of novel ultrasound beams for experiments such as animal exposure, cell exposure, tissue exposure, beam scanning experiments, and other purposes not easily achievable by transducer modification.

[0058] All of the present invention has been illustrated by the description of various embodiments, and while these embodiments have been described in considerable detail, it is not the intention of the applicant 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. The invention in its broader aspects is therefore not limited to the specific details, representative apparatus and methods, and illustrative examples shown and described. Thus, departures may be made from such details without departing from the spirit or scope of the applicant's general inventive concept.

Claims

1. A structure comprising: an outer frame comprising a first material; a disk positioned inside the outer frame, the disk comprising a second material that is compositionally different from the first material and has a higher acoustic attenuation of ultrasonic energy than the first material; A structure comprising:

2. The structure of claim 1 , wherein the second material is an open cell foam.

3. The structure of claim 1 , wherein the second material is a closed cell foam.

4. 2. The structure of claim 1, wherein the outer frame has an outer surface, and the disk is surrounded by a gap between the disk and the outer surface of the outer frame.

5. 5. The structure of claim 4, wherein said disk is centrally located inside said outer frame.

6. The structure of claim 4 , wherein the gap is an annular gap.

7. The structure of claim 1 , wherein the first material is impermeable.

8. 10. The structure of claim 1, wherein the first material is translucent to an extent that prevents visualization of the disk through the outer frame.

9. The structure of claim 1 , wherein the outer frame has a plurality of outer surfaces in an angled relationship to define a wedge shape.

10. 2. The structure of claim 1, wherein the outer frame has a first diameter and the disk has a second diameter that is smaller than the first diameter.

11. The structure of claim 1 , wherein the disk includes an aperture.

12. The structure of claim 11 , wherein the opening is circular.

13. The structure of claim 11 , wherein the opening is non-circular.

14. 1. A method comprising: In a first stage of a molding process, introducing a first layer of a first material into a mold form; inserting a disk into the form, the disk being surrounded by a gap between the disk and the form; introducing a second layer of the first material into the form during a second stage of the molding process, the second layer of the first material filling the gaps and providing a physical connection with the first layer; curing the first layer and the second layer of the first material; and A method comprising:

15. The method of claim 14 , wherein the form has a circular geometry and the peripheral gap is an annular region.

16. 15. The method of claim 14, wherein the disc is maintained at a temperature of less than 170°C during the first and second stages of the molding process.

17. The method of claim 14 , wherein the first material is not degassed prior to or during the molding process.

18. 15. The method of claim 14, wherein the disk comprises a second material that is compositionally different from the first material and has a higher acoustic attenuation of ultrasonic energy than the first material.

19. The method of claim 18 , wherein the second material is an open cell foam.

20. A test system comprising: an ultrasonic transducer configured to transmit ultrasonic energy; a first pad that allows the ultrasonic energy to be transmitted through the first pad to provide a real exposure; and a second pad that significantly attenuates the transmission of said ultrasound energy to provide a placebo exposure; A test system comprising:

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