A compact electroencephalogram-ultrasound composite multifunctional diagnosis and treatment device

Abstract

The application discloses a compact electroencephalogram-ultrasound composite multifunctional diagnosis and treatment device, which comprises a patch type ultrasonic transducer, a matching layer, an ultrasonic tissue simulation material layer and a flexible ECoG electrode, and the TM material layer, the matching layer and the patch type ultrasonic transducer are sequentially arranged from bottom to top above the flexible ECoG electrode. The compact electroencephalogram-ultrasound composite multifunctional diagnosis and treatment device can be implanted under the skull, effectively avoids the problem that the skull interferes with the ultrasonic signal, and can effectively realize ultrasonic imaging and ultrasonic focusing. Meanwhile, the flexible ECoG electrode layer used for electroencephalogram signal detection is added through structural design, and the integration of electroencephalogram-ultrasound is realized.

Description

Technical Field

[0001] This invention relates to the field of medical and health diagnosis and treatment, specifically to a compact EEG-ultrasound composite multifunctional diagnostic and treatment device. Background Technology

[0002] Since the beginning of the 21st century, research in human brain science has entered a completely new stage. Among these methods, electroencephalography (EEG) and ultrasound diagnosis have gained popularity due to their low-invasiveness and real-time monitoring capabilities.

[0003] Ultrasound possesses excellent directionality and strong reflectivity, making it easy to obtain concentrated acoustic energy. Its medical value in the field of brain surgery is receiving increasing attention. Cranial ultrasound is considered to have significant diagnostic value, serving as an important method for evaluating neonatal cranial structure and diagnosing cranial diseases. Ultrasound stimulation of specific brain regions can induce lasting changes in neural function, potentially leading to therapeutic interventions for brain function and diseases. However, in ultrasound detection and biomedical ultrasound engineering, impedance mismatch between the high-acoustic-impedance piezoelectric layer and the low-acoustic-impedance working medium causes significant acoustic energy loss. The skull has a high characteristic impedance, resulting in a large impedance mismatch with intracranial soft tissues and currently used ultrasound coupling gels. When using conventional ultrasound diagnostic methods, ultrasound waves are severely reflected at the interfaces between the skull and its interior. Combined with the skull's absorption of sound waves, only about 1% of the energy of the ultrasound signal carrying information about intracranial tissue and blood flow reaches the receiving probe, which is highly detrimental to cranial ultrasound imaging or ultrasound therapy. Therefore, the development of ultrasound devices that can be placed subskull is of great significance.

[0004] Among the many ultrasound transducers with different structures and styles, flexible ultrasound patches for ultrasound imaging and stimulation therapy are a very popular research area, showing great promise in transforming healthcare and supporting the shift towards preventative care and proactive health management. In clinical settings, they can continuously monitor high-risk patients, track fetal health in high-risk pregnancies, or monitor postoperative recovery. In 2022, a team led by Xuanhe Zhao at MIT developed an ultrasound patch the size of a postage stamp that could provide continuous 48-hour ultrasound imaging of organs (Bioadhesive ultrasound for long-term continuous imaging of diverse organs, Chonghe Wang, Xiaoyu Chen, Liu Wang, Mitsutoshi Makihata, Hsiao-Chuan Liu, Tao Zhou, Xuanhe Zhao. Science, 2022, 377, 517-523. DOI:10.1126 / science.abo254). In 2024, they launched the BAUS-E ultrasound patch, which can detect changes in organ stiffness (Yuk, H., Varela, CE, Nabzdyk, CSet al. Dry double-sided tape for adhesion of wet tissues and devices. Nature). 575,169-174(2019).https: / / doi.org / 10.1038 / s41586-019-1710-5), which is expected to be applied in clinical practice. In 2022, the team led by Sheng Xu at the University of California, San Diego developed a novel "patch-type" cardiac ultrasound imaging device (A wearable cardiac ultrasound imager[J].Nature[2024-08-28].DOI:10.1038 / s41586-022-05498-z.), which can continuously extract important cardiac status information of patients in both exercise and non-exercise states, attracting widespread attention in the industry; in 2024, the team further developed an ultrasound patch that can be used for transcranial imaging (Zhou,Sai, et al.Transcranialvolumetric imaging using a conformal ultrasound patch.Nature 629.8013(2024):810-818.), which can be used for non-invasive clinical cerebral blood flow detection. It is evident that the patching, flexibility, and miniaturization of ultrasonic transducers have considerable application potential in brain science-related research fields.

[0005] Electroencephalography (EEG) is a fundamental characteristic of brain neural activity, reflecting the physiological state and information encoding of neurons. EEG signals have been applied in sleep monitoring, and in the diagnosis and treatment of diseases such as epilepsy and Parkinson's disease. However, there is still significant room for research into the synergistic application of EEG and ultrasound, and the development of integrated devices that can form a functional closed loop. Electrode technology (EEG) is an electronic device that records the electrophysiological activity of neurons and is an important tool for studying EEG. Based on the degree of invasiveness, it is divided into three types: non-invasive scalp EEG (EEG), semi-invasive cortical EEG (ECoG), and invasive deep brain electrodes (DPS). ECoG electrodes are mostly sheet-like structures, offering higher precision than EEG electrodes while being more convenient, economical, and less invasive than DPS electrodes. Commercially available ECoG electrodes are already commonly used in clinical practice for invasive monitoring of epilepsy patients. They can achieve good structural compatibility and integration with patch-type ultrasound transducers. Further flexible and thin-layer designs are expected to reduce the mutual interference between different functional layers of the device. Therefore, designing a compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device based on flexible ECoG electrodes and patch-type ultrasound transducers is worthy of research and feasible. Summary of the Invention

[0006] The purpose of this invention is to provide a compact EEG-ultrasound composite multifunctional diagnostic and therapeutic device that can be implanted under the skull, effectively avoiding the problem of skull interference with ultrasound signals and effectively realizing ultrasound imaging and ultrasound focusing; at the same time, through structural design, a flexible ECoG electrode layer that can be used for EEG signal detection is added, realizing integrated multifunctional diagnostic and therapeutic EEG-ultrasound composite.

[0007] This invention provides the following technical solution:

[0008] This invention proposes a compact EEG-ultrasound composite multifunctional diagnostic and therapeutic device, which includes: a patch-type ultrasound transducer, a matching layer, an ultrasound tissue-mimicking (TM) material layer, and a flexible ECoG electrode. The TM material layer, the matching layer, and the patch-type ultrasound transducer are arranged sequentially from bottom to top above the flexible ECoG electrode.

[0009] Wherein: the patch-type ultrasonic transducer can realize ultrasonic imaging or focused ultrasound function; the matching layer is used to realize acoustic impedance matching between the patch-type ultrasonic transducer and the TM material layer; the TM material refers to a material that imitates the ultrasonic wave propagation characteristics of human soft tissue, and has similar properties to human tissue such as density, acoustic impedance, sound velocity or absorption coefficient; the flexible ECoG electrode should have sufficiently low bending stiffness to be able to tightly bond with the surface of brain tissue without producing obvious gaps.

[0010] Furthermore, in use, the flexible ECoG electrode of the compact EEG-ultrasound multifunctional diagnostic and therapeutic device is attached to the surface of the meninges.

[0011] Furthermore, the patch-type ultrasonic transducer is a piezoelectric ultrasonic transducer containing a two-dimensional array of multiple piezoelectric elements, which can realize ultrasonic imaging or focused ultrasonic stimulation functions.

[0012] Furthermore, the thickness of the TM material layer is 1–5000 μm, and it has a certain deformation capability.

[0013] Furthermore, the flexible ECoG electrode is a layered structure with low bending stiffness that can ensure close contact with the surface of brain tissue. It typically has one or more conductive contacts that are in direct contact with brain tissue and can detect ECoG signals at corresponding locations.

[0014] Furthermore, the flexible ECoG electrode has a sufficiently small impact on the patch-type ultrasonic transducer and will not affect its normal operation. The thickness of the flexible ECoG electrode can be designed to be smaller than the wavelength corresponding to the operating frequency of the patch-type ultrasonic transducer. The thickness should be multiples of the wavelength (the smaller the thickness, the better the effect) or the thickness should be an integer multiple of the half wavelength corresponding to the working frequency of the patch-type ultrasonic transducer.

[0015] Limiting the thickness of the flexible ECoG electrode effectively reduces obstruction of the ultrasound module.

[0016] Furthermore, the thickness of the flexible ECoG electrode is 1–1000 μm. The thickness of the patch-type ultrasonic transducer is 1–2000 μm. The overall thickness of the device is 100–20000 μm.

[0017] The implementation principle of this invention is as follows:

[0018] (1) Design principles of the matching layer

[0019] To achieve acoustic matching between brain tissue and the piezoelectric element of the patch-type ultrasound transducer, a matching layer was placed beneath the piezoelectric element to improve transducer performance (e.g., improve sensitivity, broaden bandwidth, and reduce distortion). The acoustic impedance of human soft tissue is approximately 1.5 × 10⁻⁶. 6 Pa·S / m, the acoustic impedance of the piezoelectric element is as high as 30×10⁻⁶ Pa·S / m. 6 The difference between the two is very large, with a pressure of approximately Pa·S / m.

[0020] When a plane wave is incident perpendicularly at the interface between two media, if Z1 and Z2 represent the acoustic impedances of the first and second media respectively, then:

[0021] Reflectance coefficient

[0022]

[0023] Transmission coefficient

[0024]

[0025] Therefore, radiating ultrasound waves from piezoelectric ceramics into human soft tissue results in a high reflection coefficient and a low transmission coefficient, with most sound waves being reflected. As can be seen from the formula, when the acoustic impedances of the two media are similar (Z1≈Z2), the acoustic intensity reflectivity approaches 0, and the acoustic intensity transmittance approaches 1. Therefore, a matching layer can be added to compensate for the acoustic impedance mismatch when ultrasound waves pass through the interface.

[0026] The function of the matching layer is determined by its characteristic impedance and size. Different frequencies of sound waves require matching layers with different thicknesses. The effectiveness of the matching layer is related to the frequency of the propagating sound waves. Currently, there are various structural, material, or size designs that can be applied to the preparation of matching layers.

[0027] (2) Design of TM materials and flexible ECoG electrodes

[0028] TM material has a certain degree of flexibility and deformation capability. The flexible ECoG electrode involved in this invention has a small stiffness coefficient. The existence of this two-layer structure can make the compact EEG-ultrasound composite multifunctional diagnostic and therapeutic device fit closely to the surface of brain tissue, ensuring the effectiveness of the device.

[0029] (3) Design of the thickness of the flexible ECoG electrode layer

[0030] An intermediate layer medium (equivalent to the flexible ECoG electrode layer in this invention) with a thickness of D and an impedance characteristic of R2 = ρ2c2 is placed between media (media I and media III, equivalent to the TM material layer and biological brain tissue in this invention) with a characteristic impedance of R1 = ρ1c1. Figure 1 A coordinate system is established as shown. In the formula, ρ represents the density of the medium, c represents the sound velocity of the medium, and λ represents the wavelength of the ultrasonic wave.

[0031] When the planar acoustic wave (p) emitted by the patch transducer i ,v i When a wave is incident perpendicularly on the interface of the intermediate layer (medium II), a portion of it is reflected back into medium I, thus forming a reflected wave (p). 1r ,v 1r Another portion penetrates into the intermediate layer and is denoted as (p). 2t ,v 2t When sound waves (p) 2t ,v 2t When the material travels to another interface of the intermediate layer, due to the change in impedance characteristics, a portion of it will return to the intermediate layer, denoted as (p). 2r ,v 2r The remaining portion penetrates into the ρ1c1 medium (medium III) after the intermediate layer, ignoring the re-reflection of the transmitted wave.

[0032] set up Therefore, it can be deduced that the sound intensity transmission coefficient is equal to the sound intensity I of the transmitted wave. t With the incident wave acoustic intensity I i The ratio:

[0033]

[0034] In the formula,

[0035] From this formula, we can conclude that:

[0036] when When cos k2D≈1 and sink2D≈0, we have t≈1. That is, when the thickness D of the flexible ECoG electrode layer in the middle is small enough, the sound wave can be basically completely transmitted. The smaller the thickness D, the better the sound wave transmission effect.

[0037] In addition, when k2D=nπ, the thickness of the flexible ECoG electrode layer is an integer multiple of half the wavelength, and t≈1. The principle is the same as the sound transmission principle of the half-wave acoustic transducer commonly used in ultrasonic technology, and it will not affect the normal operation of the patch ultrasonic transducer.

[0038] The beneficial effects of this invention are as follows:

[0039] The compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device provided by this invention can realize ultrasound imaging or focused ultrasound stimulation functions, while simultaneously using ECoG electrodes to detect EEG signals. This invention achieves acoustic impedance matching between the human body and the ultrasound transducer through the addition of a matching layer. The TM material layer and flexible ECoG electrodes make the lower surface of the compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device flexible, allowing for close contact with the brain tissue surface. The thickness of the ECoG electrode layer is designed to ensure the effectiveness of the ultrasound.

[0040] The device provided by this invention can be used to image or focus ultrasound stimulation of lesions in the brain in real time, while detecting ECoG signals in the brain, thereby enabling a more comprehensive detection and characterization of the brain state, and is expected to play a role in the fields of brain science research and diagnosis and treatment of brain diseases. Attached Figure Description

[0041] Figure 1 This is a schematic diagram illustrating the principle of the present invention;

[0042] Figure 2 This is a schematic diagram of the compact EEG-ultrasound multifunctional diagnostic and therapeutic device in the embodiment;

[0043] Figure 3 This is a cross-sectional view of the compact EEG-ultrasound multifunctional diagnostic and therapeutic device in the embodiment;

[0044] Figure 4 A method for fabricating a compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device is provided as an example.

[0045] Figure 5 These are photographs of the front and back of the device in the example. Detailed Implementation

[0046] The present invention will be further described below with reference to the accompanying drawings and embodiments. Here, the embodiments and descriptions of the present invention are used to explain the present invention, but are not intended to limit the present invention.

[0047] Example

[0048] like Figure 2 and Figure 3 As shown, the compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device provided in this embodiment includes: a patch-type ultrasound transducer 1, a matching layer 2, a TM material layer 3, and a flexible ECoG electrode 4. In use, the flexible ECoG electrode 4 is attached to the surface of brain tissue and in close contact. The TM material layer 3, the matching layer 2, and the patch-type ultrasound transducer 1 are sequentially arranged above the flexible ECoG electrode 4 from bottom to top. The rear end of the flexible ECoG electrode 4 is connected to an EEG signal acquisition and processing device, and the rear end of the ultrasound transducer 1 is connected to a programmed ultrasound imaging or focused ultrasound device.

[0049] In this embodiment, the TM material layer and the flexible ECoG electrode can achieve a certain degree of deformation, thereby better conforming to the surface of brain tissue, making the device in close contact without gaps, which can better ensure the accuracy of ECoG signals and the effectiveness of ultrasound.

[0050] For ease of understanding, please refer to Figure 4 The method for manufacturing the compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device provided in this embodiment includes steps S1 to S4:

[0051] S1. Based on the acoustic impedance Z1 of the piezoelectric part in the patch-type ultrasonic transducer and the acoustic impedance Z2 of the brain tissue (which is also the approximate acoustic impedance of the TM material layer), select a matching layer material, requiring the material's acoustic impedance Z... m Choose to be as close as possible or slightly higher Such as Al2O3-epoxy resin mixture.

[0052] S2. Based on the wavelength λ corresponding to the working center frequency (1.5MHz) of the patch-type ultrasonic transducer, prepare a substrate with a thickness of [missing information] on the working surface of the patch-type ultrasonic transducer. A single-layer matching layer. In this step, the thickness and shape of the matching layer can be controlled using a mold casting and curing method.

[0053] S3. Add the TM material layer onto the matching layer. In this example, agarose is selected as the TM material matrix. The specific method is to dissolve the agarose powder in water at 120°C, stir until clear and transparent, and then put it into the mold to solidify. Before the agarose is completely solidified, it is brought into contact with the matching layer until the two are firmly bonded.

[0054] S4. Add the flexible ECoG electrode before the TM material layer is fully cured. The flexible ECoG electrode is prepared by flexible 3D printing. It is thin and has good flexibility. The electrode thickness is only about 100μm without external pressure, and the contact direction should be consistent with the working surface direction of the patch ultrasonic transducer. The process is basically completed after the TM material layer is fully cured.

[0055] After completing the above steps, in order to improve the stability of the device, an unobstructed housing can be added or the device can be fully flexibly packaged.

[0056] Figure 5 These are front and back photos of the device from the embodiment. The image shows a physical example of an assembly with a 36-element ultrasonic patch and a 16-channel thin-layer flexible ECoG electrode (before overall packaging), demonstrating the small area and high density of the device (36 ultrasonic elements and 16 ECoG electrode channels within a 2cm*2cm area). The overall thickness is in the millimeter range, meeting the requirements for subskull placement.

[0057] In summary, this embodiment provides a compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device. This device is small in area and thin in thickness, allowing it to be placed under the skull. It enables ultrasound imaging or focused ultrasound stimulation while simultaneously detecting EEG signals using ECoG electrodes. The addition of a single-layer matching layer achieves acoustic impedance matching between the human body and the ultrasound transducer. The TM material and flexible ECoG electrodes give the lower surface of the compact EEG-ultrasound hybrid multifunctional diagnostic and therapeutic device flexibility, allowing for close contact with the brain tissue surface. Furthermore, the thickness of the ECoG electrode layer is designed to ensure the effectiveness of the ultrasound. This embodiment can be used for real-time imaging or focused ultrasound stimulation of brain lesions, while simultaneously detecting ECoG signals in the brain. By connecting to backend devices, it can perform multi-dimensional detection and characterization of brain states.

[0058] It should be noted that the above description is merely one embodiment of the present invention and is not intended to limit the invention. For those skilled in the art, the present invention can have various modifications and variations. For example, the design principle of the matching layer can employ a traditional single-layer matching layer, or it can be made using multi-layer matching layers, density-gradient matching layer materials, or structurally designed matching layer materials. Any design that can achieve acoustic impedance matching should be included. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A compact electroencephalogram-ultrasound composite multifunctional diagnosis and treatment device, characterized in that, The device comprises a patch ultrasonic transducer, a matching layer, an ultrasonic tissue-mimicking material layer and a flexible ECoG electrode, and the ultrasonic tissue-mimicking material layer, the matching layer and the patch ultrasonic transducer are sequentially arranged from bottom to top above the flexible ECoG electrode. In use, the flexible ECoG electrode in the device is attached to the surface of the dura mater under the skull. The thickness of the flexible ECoG electrode is 1-1000 μm. The thickness of the patch ultrasonic transducer is 1-2000 μm. The thickness of the ultrasonic tissue-mimicking material layer is 1-5000 μm. The overall thickness of the device is 100-20000 μm.

2. The compact electroencephalogram-ultrasound composite multifunctional diagnosis and treatment device according to claim 1, characterized in that, The patch ultrasonic transducer is a piezoelectric ultrasonic transducer, which comprises a two-dimensional array of multiple piezoelectric vibration elements. 3.The compact electroencephalogram-ultrasound composite multifunctional diagnosis and treatment device according to claim 1, characterized in that, The thickness of the flexible ECoG electrode is less than 1 / 8 of the wavelength corresponding to the working frequency of the patch ultrasonic transducer. times. 4.The compact electroencephalogram-ultrasound composite multifunctional diagnosis and treatment device according to claim 1, characterized in that, The thickness of the flexible ECoG electrode is an integer multiple of the half wavelength corresponding to the working frequency of the patch ultrasonic transducer.

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