An expandable contractible flexible graded matching layer for matching a skull and its preparation method and application

Abstract

The application discloses an expandable and contractible flexible gradual matching layer for matching a skull, the matching layer comprises a plurality of hydrogel layers with different densities, and in the direction of increasing density, the acoustic impedance is exponentially distributed in a gradient from one end of the matching layer to the other end; wherein the matching layer adjusts the range of acoustic impedance by expansion and contraction, and the expansion and contraction are respectively realized by water absorption and water loss. The application also discloses a preparation method of the expandable and contractible flexible gradual matching layer for matching a skull and application of the preparation method in the preparation of products for transcranial ultrasound treatment and intracerebral ultrasound focusing imaging. The matching layer provided by the application adjusts the impedance range by expansion and contraction, meets different acoustic impedance change gradient requirements, and has good acoustic intensity transmission performance when applied to cranial ultrasound imaging and focused ultrasound treatment.

Description

Technical Field

[0001] This invention belongs to the field of acoustic impedance matching materials technology, and specifically relates to an expandable and contractile flexible gradient matching layer for matching the skull, its preparation method and application. Background Technology

[0002] Ultrasound plays a vital role in the fields of medicine and biomedical engineering, and is widely used in clinical testing and medical research due to its non-invasive, real-time, and safe nature. It can provide high-resolution images for the detection and diagnosis of various diseases, such as tumors, cardiovascular diseases, and pregnancy monitoring. However, some challenges exist in ultrasound applications, such as the influence of the skull on ultrasound transmission.

[0003] In the transmission of ultrasound through the skull, a significant impedance mismatch exists between the high acoustic impedance of the skull and the low acoustic impedance of biological tissues, posing a series of challenges to ultrasound waves as they penetrate the skull. This impedance mismatch creates a potential barrier at the skull interface, causing most of the ultrasound energy to be reflected by the skull and unable to penetrate effectively. This presents a challenge for diagnosing intracranial lesions and monitoring brain activity, as traditional ultrasound techniques struggle to penetrate the skull to obtain clear and accurate images.

[0004] Addressing the challenges posed by the skull is crucial for developing more advanced intracranial ultrasound imaging techniques. Researchers have explored various approaches to meet this challenge, including improving ultrasound probe design, optimizing ultrasound frequencies and beamforming, and utilizing advanced signal processing techniques. These efforts aim to increase the penetration depth and resolution of intracranial ultrasound, enabling it to play a greater role in the early diagnosis and treatment monitoring of brain diseases.

[0005] Currently, commonly used matching layer technology involves adding several layers of matching layer material with a gradient distribution of characteristic impedance. This results in a gradual change in acoustic impedance from one end of the matching layer to the other, thus broadening the transducer bandwidth. For example, Chinese Patent Publication No. CN112040382A discloses a high-frequency broadband underwater acoustic transducer based on an acoustic impedance gradient matching layer, comprising a backing, an active material layer, a uniform matching layer, a gradient matching layer, and a waterproof and sound-permeable layer. These layers are arranged sequentially. The backing is tightly connected to the active material layer; the uniform matching layer is tightly connected to the active material layer; the gradient matching layer is tightly connected to the uniform matching layer; and the waterproof and sound-permeable layer is tightly connected to the gradient matching layer. The gradient matching layer includes a gradient matching layer frame and a filling cone, and the characteristic impedance value of the gradient matching layer exhibits an exponential decay along the sound propagation direction. Another example is Chinese Patent Publication No. CN109535650A, which discloses a resin-based acoustic matching layer with an impedance gradient for an ultrasonic transducer and its manufacturing method, belonging to the fields of composite materials and functional materials technology. The resin-based acoustic matching layer is composed of epoxy resin, polystyrene powder, alumina powder, tungsten carbide powder, silica / cerium oxide composite micro / nanospheres, butyl glycidyl ether, polyetheramine, resorcinol and diethylenetriamine.

[0006] However, the following problems still exist: impedance mismatch still exists between the matching layers, resulting in energy loss; the frequency of high-frequency ultrasonic transducers is high, the required matching layer thickness is small, the processing accuracy is difficult to control, and the cost is high; the impedance range that the matching layer can match is fixed, and it cannot be easily adjusted when applied to different individuals. Summary of the Invention

[0007] The purpose of this invention is to provide an expandable and contractile flexible gradient matching layer for matching the skull, which can adjust the impedance range through expansion and contraction to meet different acoustic impedance gradient requirements; and has good acoustic intensity transmission performance when applied to cranial ultrasound imaging and focused ultrasound therapy.

[0008] This invention provides the following technical solution:

[0009] An expandable and contractile flexible gradient matching layer for matching the skull, the matching layer comprising several hydrogel layers of different densities, wherein the acoustic impedance is distributed in an e-exponential gradient from one end to the other along the direction of increasing density.

[0010] The matching layer adjusts the range of acoustic impedance by expanding and contracting, and expands and contracts by absorbing and losing water, respectively.

[0011] In this invention, the cross-sectional thickness of each layer is uniform along the height / thickness direction of the matching layer structure; taking the plane containing the upper surface of the skull as the xy plane, the acoustic impedance of the matching layer varies exponentially in the z-direction. The end of the matching layer with higher density faces the skull.

[0012] In this invention, multiple layers of hydrogels with different densities are integrated into a single structure. The multiple hydrogels adhere tightly to each other and will not peel off. This results in a better effect of the acoustic impedance gradually changing exponentially from one end of the matching layer to the other. Furthermore, the multiple hydrogels will not detach during expansion and contraction.

[0013] In this matching layer, the end with the lowest density has an acoustic impedance similar to water, while the end with the highest density is close to and in direct contact with the human skull. The term "close to" means that the maximum acoustic impedance of the matching layer is between 80% and 120% of the acoustic impedance of the skull. The acoustic impedance of the human skull is approximately 6.5 μm.

[0014] The hydrogel layer comprises hydrogel or hydrogel and solid particles, wherein the solid particles are selected from metal nanoparticles or metal oxide nanoparticles. That is, the density of each hydrogel layer is adjusted by doping with solid particles. Solid particles with good hydrophilicity and biocompatibility are used; the solid particles are selected from metal nanoparticles or metal oxide nanoparticles.

[0015] The hydrogel is selected from polyacrylamide.

[0016] Preferably, the hydrogel is polyacrylamide, and the polyacrylamide material is a material with an acoustic impedance similar to that of the medium to be tested. For example, the medium to be tested is generally water or human tissue, with an acoustic impedance of 1.5 μm. Therefore, the end with the lowest acoustic impedance can be selected from polyacrylamide hydrogels without solid particles.

[0017] Furthermore, since the acoustic impedance of polyacrylamide material is almost identical to that of water, during the process of the matching layer absorbing water and expanding and losing water and shrinking, the acoustic impedance at the end with the smallest acoustic impedance always remains at 1.5mrayl, which can then match the acoustic impedance between human tissues and different individuals' skulls.

[0018] The metal oxide nanoparticles are selected from one or a combination of at least two of the following: titanium dioxide nanoparticles, iron oxide nanoparticles, iron tetroxide nanoparticles, or silicon dioxide nanoparticles.

[0019] Taking the plane containing the upper surface of the skull as the xy plane, the acoustic impedance of several hydrogel layers in the matching layer all satisfy the following:

[0020] y = A + Be Cx

[0021] Where A+B=Z1, Where Z1 represents the required low acoustic impedance, Z2 represents the required high acoustic impedance, and d represents the total thickness of the matching layer. In this invention, the low acoustic impedance is represented by the acoustic impedance of water, and the high acoustic impedance by the acoustic impedance of the skull. Without considering absorption, a gradually changing matching layer whose acoustic impedance follows this rule minimizes the reflection of ultrasound waves in the direction of sound propagation, thus exhibiting better transmission performance. The calculation process is relatively complex, involving the following steps for key coefficients:

[0022] The characteristic impedance of the dielectric is:

[0023]

[0024] Where p represents sound pressure, v consists of waves propagating in both directions, ρ is the density of the material, and c is the speed of sound of ultrasound propagating in the material.

[0025] For non-uniform layers, they are usually divided into n incremental layers, where for the i-th layer, the parameter α is calculated. i As shown below, where d represents the thickness.

[0026] α i =(1 / 2d i )ln[z(x i+1 ) / z(x i )]

[0027] For a matching layer with an exponentially varying acoustic impedance, its energy reflection coefficient E R for:

[0028]

[0029] Where f represents the frequency of the ultrasound.

[0030] Define the matching layer thickness as equal to half the wavelength. Calculations show that waves with frequencies higher than half the wavelength will be transmitted through the e-exponentially graded matching layer with a reflection loss of less than 10%.

[0031] Preferably, in the unexpanded / uncontracted state, the acoustic impedance of each of the several hydrogel layers in the matching layer satisfies: y = 1.0 + 0.47e 1.83x .

[0032] For the unexpanded / uncontracted state, the density ρ0 is:

[0033]

[0034] ρ1 is the density after expansion, and ρ2 is the density after contraction:

[0035]

[0036]

[0037] The present invention also provides a method for preparing the above-mentioned expandable and contractile flexible gradient matching layer for matching the skull, the method comprising:

[0038] (1) Preparation of hydrogel layers with different densities: Based on the selected density, prepare hydrogels without doping or / and doped with solid particles of different masses;

[0039] (2) Preparation of flexible gradient matching layer: First, pour the bottom layer hydrogel with the highest density into the mold and complete the curing. Then, pour the hydrogel with the second highest density on it and complete the curing. According to the density from large to small, the pouring is completed in sequence. After curing, it serves as the matching layer.

[0040] When it is necessary to adjust the range of acoustic impedance of the matching layer, the method further includes:

[0041] (3) Adjust the range of acoustic impedance by expanding or contracting the matching layer: expand the matching layer by immersing it in water or buffer solution; contract the matching layer by heating it (e.g., in an oven).

[0042] In step (2), the cross-section of the mold substrate is circular. In step (3), its density is changed by expansion and contraction, thereby changing the acoustic impedance range of the matching layer.

[0043] The present invention also provides an application of the above-described expandable and contractile flexible gradient matching layer for matching the skull in the preparation of products for cranial ultrasound imaging and (high intensity) focused ultrasound therapy.

[0044] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0045] (1) Compared with the traditional uniform matching layer, the acoustic impedance of the matching layer is distributed in an e-exponential gradient. The acoustic impedance of the matching layer changes from the acoustic impedance of the skull to the acoustic impedance of the working medium in an e-exponential gradient.

[0046] (2) The acoustic impedance change of the matching layer in this invention can be adjusted by changing the density of the matching layer through expansion and contraction, which can meet different acoustic impedance change gradient requirements without the need for re-customization.

[0047] (3) In the application scenario of ultrasonic testing, the matching layer has good flexibility, which can reduce the sound energy loss caused by poor bonding, and will not affect the matching performance. Attached Figure Description

[0048] Figure 1 Here are schematic diagrams of the expandable and contractible flexible gradient matching layer in Example 1: (a) a cross-sectional view of the matching layer along the thickness direction, and (b) a top view of the matching layer.

[0049] Figure 2The following are actual images of the polyacrylamide hydrogel without solid particles in Example 1: (a) hydrogel before expansion and shrinkage, (b) hydrogel after expansion;

[0050] Figure 3 The following are actual images of the monolayer polyacrylamide hydrogel with uniform density doped with solid particles in Example 1: (a) hydrogel before expansion and shrinkage, (b) hydrogel after expansion;

[0051] Figure 4 Examples 1 show the following physical images of a flexible, gradient matching layer containing multiple layers of hydrogels with different densities that can expand and contract: (a) matching layer before expansion and contraction, (b) matching layer after expansion, (c) matching layer after contraction, and (d) cross-sectional view of the matching layer along the thickness direction.

[0052] Figure 5 This is a schematic diagram of the ultrasonic test using COMSOL simulation.

[0053] Figure 6 The results of simulation using COMSOL are as follows: (a) is the sound intensity transmission coefficient obtained by simulation in COMSOL for Example 1; (b) is the sound intensity transmission coefficient obtained by simulation in COMSOL for Comparative Example 1. Detailed Implementation

[0054] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. Here, the embodiments and descriptions of the present invention are used to explain the invention, but are not intended to limit the invention.

[0055] The present invention proposes an expandable and contractile flexible gradient matching layer with acoustic impedance varying exponentially (e). Its expandable and contractile hydrogel material is polyacrylamide, and the filler material is nano-sized titanium dioxide particles. The specific preparation method is as follows:

[0056] (1) Preparation of hydrogels with different densities: Based on the selected density, prepare hydrogels doped with different masses of solid particles;

[0057] In this model, the plane containing the upper surface of the skull is taken as the xy-plane, and the acoustic impedance of the matching layer exhibits an exponential (e) variation in the z-direction. The matching layer can expand and contract through water loss and absorption, thereby controlling its impedance range. The matching layer consists of multiple layers of hydrogel with varying densities, and a cross-sectional view along its thickness is shown below. Figure 1 As shown in (a); viewed from the end with the lowest density, as... Figure 1 As shown in (b) of the diagram.

[0058] (2) Preparation of flexible gradient matching layer: First, pour the bottom layer hydrogel with the highest density into the mold and complete the curing. Then, pour the hydrogel with the second highest density on it and complete the curing. According to the density from large to small, complete the pouring in sequence. After curing, take out the matching layer.

[0059] (3) Swelling and shrinkage: Soak the matching layer in the buffer solution and let it stand for a certain time to complete the swelling; put the matching layer in the oven and heat it for a certain time to complete the shrinkage.

[0060] It should be noted that the directional indication in the embodiments of the present invention is only used to explain the relative positional relationship and movement of the components in a specific posture. When the specific posture changes, the directional indication will also change accordingly.

[0061] In this invention, unless otherwise explicitly specified and limited, the terms "connection," "fixing," etc., should be interpreted broadly. For example, "fixing" can mean a fixed connection, a detachable connection, or an integral part; it can mean a direct connection or an indirect connection through an intermediate medium, unless otherwise explicitly limited. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0062] Furthermore, the technical solutions of the various embodiments of the present invention can be combined with each other, but only if they are based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such combination of technical solutions does not exist and is not within the scope of protection claimed by the present invention.

[0063] Example

[0064] like Figure 2 to- Figure 4 The expandable and shrinkable flexible gradient matching layer with an exponentially varying acoustic impedance provided in this embodiment is prepared from several layers of polyacrylamide hydrogel with different densities of undoped and doped solid particles. It can expand after absorbing water and shrink after dehydration. Along the direction of increasing matching layer density, the acoustic impedance is gradually distributed from one end of the matching layer to the other.

[0065] In this embodiment, the acoustic impedance in the unexpanded / uncontracted state satisfies: y = 1.0 + 0.47e 1.83x .

[0066] In this embodiment, the doped solid particles are nano-titanium dioxide powder, uniformly mixed with titanium dioxide and polyacrylamide gel at mass ratios of 0:1, 0.58:1, 0.73:1, 0.92:1, and 1.15:1, respectively, in ascending order of density. The acoustic impedance of titanium dioxide is approximately 30 mRayl, and that of the polyacrylamide gel is 1.5 mRayl. The test medium is water or human tissue, with an acoustic impedance of 1.5 mRayl. Thus, the acoustic impedance gradient variation range under unexpanded / uncontracted conditions is 3.22 mRayl–1.5 mRayl.

[0067] The image shows a physical example of a polyacrylamide hydrogel without solid particles. Figure 2 As shown in (a) above, the actual image of the hydrogel after swelling is as follows: Figure 2 As shown in (b) of the figure. A physical image of the monolayer of polyacrylamide hydrogel layer doped with solid particles of uniform density prepared in this embodiment is shown below. Figure 3 As shown: Figure 3 (a) in the image represents the hydrogel layer in its unexpanded and unshrunken state. Figure 3 (b) shows the hydrogel layer after expansion; the overall physical image of the matching layer prepared in this embodiment is shown below. Figure 4 As shown in (a) above, the physical image after the matching layer dilation is as follows: Figure 4 As shown in (b) above, the physical image after the matching layer has shrunk is as follows: Figure 4 As shown in (c) in 5, the cross-sectional view of the matching layer along the thickness direction is shown in (d) in 5.

[0068] For the matching layer provided in this embodiment, after absorbing water and swelling, the volume of the matching layer can expand to a maximum of 8 times its original size, at which point the acoustic impedance gradient changes within the range of 1.72 mrayl-1.5 mrayl. During dehydration and shrinkage, theoretically, the volume can shrink to approximately the volume of titanium dioxide powder. However, considering practical use, we assume the volume shrinks to 1 / 8 of its original size, at which point the acoustic impedance gradient changes within the range of 15.3 mrayl-1.5 mrayl. Therefore, when the test medium is fixed as water or human tissue, the acoustic impedance range that can be matched at the other end is 1.72 mrayl-15.3 mrayl.

[0069] A simulation was performed in the time domain using COMSOL Multiphysics software. A schematic diagram of the simulation is shown below. Figure 5 When the acoustic impedance of the matching layer is in the range of 6.5mrayl-1.5mrayl, the obtained acoustic intensity transmission coefficient is... Figure 6 As shown in (a), the sound intensity transmission coefficient remains in a high range between 0.5MHz and 2.5MHz, indicating that this gradient matching layer has better sound intensity transmission performance than the traditional matching layer.

[0070] Comparative Example 1

[0071] Comparative Example 1 uses a conventional 1 / 4 wavelength matching layer, and its material is the same as that of Example 1. It is obtained by uniformly mixing titanium dioxide powder and polyacrylamide hydrogel at a mass ratio of 1.1:1, with a thickness of about 3 mm.

[0072] The sound intensity transmission coefficient was obtained by performing a simulation in the time domain using COMSOL Multiphysics software, as shown below. Figure 6In (b), although the sound intensity transmission performance is very good at its matched 2MHz, the sound intensity transmission performance at other frequencies is significantly worse than that of the e-index graded matching layer.

[0073] The specific embodiments described above illustrate the technical solution and beneficial effects of the present invention in detail. It should be understood that the above description is only the most preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, additions, and equivalent substitutions made within the scope of the principles of the present invention should be included within the protection scope of the present invention.

Claims

1. An expandable and contractile flexible gradient matching layer for matching the skull, characterized in that, The matching layer comprises several hydrogel layers with different densities. Along the direction of increasing density, the acoustic impedance gradually changes from one end of the matching layer to the other in an e-exponential gradient. The matching layer adjusts the range of acoustic impedance by expanding and contracting, and expands and contracts by absorbing and losing water, respectively. The hydrogel layer comprises hydrogel and solid particles, wherein the solid particles are selected from metal nanoparticles or metal oxide nanoparticles. The hydrogel is selected from polyacrylamide; Taking the plane containing the upper surface of the skull as the xy plane, the acoustic impedance of several hydrogel layers in the matching layer all satisfy the following: y=A+Be Cx Where A+B=Z1, Where Z1 is the required low acoustic impedance, Z2 is the required high acoustic impedance, and d is the total thickness of the matching layer. The acoustic impedance of several hydrogel layers in the matching layer all satisfy: y = 1.0 + 0.47e 1.83x .

2. The expandable and contractile flexible gradient matching layer for matching the skull according to claim 1, characterized in that, The metal oxide nanoparticles are selected from one or a combination of at least two of titanium dioxide nanoparticles, iron oxide nanoparticles, or iron tetroxide nanoparticles.

3. A method for preparing an expandable and contractile flexible gradient matching layer for matching the skull as described in any one of claims 1-2, characterized in that, The method includes: (1) Preparation of hydrogel layers with different densities: Based on the selected density, prepare hydrogels without doping or / and doped with solid particles of different masses; (2) Preparation of flexible gradient matching layer: First, pour the bottom layer hydrogel with the highest density into the mold and complete the curing. Then, pour the hydrogel with the second highest density on it and complete the curing. According to the density from large to small, the pouring is completed in sequence. After curing, it serves as the matching layer.

4. The method for preparing an expandable and contractile flexible gradient matching layer for matching the skull according to claim 3, characterized in that, When it is necessary to adjust the range of acoustic impedance of the matching layer, the method includes: (3) Adjust the range of acoustic impedance by expanding or contracting the matching layer: expand the matching layer by immersing it in water; contract the matching layer by heating it.

5. The use of the expandable and contractile flexible gradient matching layer for matching the skull as described in any one of claims 1-2 in the preparation of products for cranial ultrasound imaging and focused ultrasound therapy.

Images