Real-time navigation method and system for ultrasound transducer for transcranial ultrasound stimulation

Abstract

The present application provides a real-time navigation method for an ultrasonic transducer for transcranial ultrasonic stimulation, comprising the following steps: (b) performing forward transcranial ultrasonic sound field simulation calculation based on the initial position and angle of the ultrasonic transducer to obtain the position of the simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer; (c) using the gradient descent method to calculate the position and angle of the ultrasonic transducer in the intermediate round; (d) performing forward transcranial ultrasonic sound field simulation calculation based on the position and angle of the ultrasonic transducer in the intermediate round calculated in step (c) to obtain the simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer in this round; (e) repeating and iterating steps (c) and (d) to obtain the optimal position and angle of the ultrasonic transducer for navigation; this method can effectively reduce the ultrasonic focus position offset error caused by the skull, and guide the placement of the ultrasonic transducer so that the focus of the ultrasound falls accurately on the predetermined stimulation target in the skull.

Description

Technical Field

[0001] The present invention relates to the fields of neural regulation and brain function detection, and in particular to a real-time navigation method and system of an ultrasonic transducer for transcranial ultrasonic stimulation. Background Art

[0002] Transcranial ultrasound stimulation (TUS) utilizes low-frequency, low-intensity focused ultrasound, which boasts high spatial resolution and a deep focal depth compared to other common non-invasive neuromodulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). Currently, a number of studies have demonstrated the immediate and sustained regulatory effects of TUS on brain neural activity in healthy subjects, inducing plastic changes in the human cerebral cortex. Clinical studies have also reported the application of TUS in neurological or psychiatric brain disorders such as epilepsy, stroke, and impaired consciousness. These findings suggest that TUS has great potential for the study of human brain function and the clinical treatment of brain diseases. However, to fully utilize the advantages of TUS's high spatial resolution, the ultrasound waves must be precisely focused on the target therapeutic site after passing through brain tissue, such as the skull. This is technically challenging and requires overcoming various difficulties arising from various factors.

[0003] In the current practical application of TUS, users generally determine the rough position of the ultrasound transducer manually, or use a navigation system suitable for other neuromodulation technologies such as TMS to guide the placement of the ultrasound transducer. Since the direction of ultrasound propagation will be deflected when the ultrasound passes through the skull and other brain tissues, the focus in the skull will be offset and distorted in shape relative to the focus in the absence of brain tissue such as the skull. Existing navigation systems suitable for other neuromodulation technologies fail to take into account the impact of the transcranial propagation of the sound field on the focal position, making it difficult to guide the placement of the ultrasound transducer to the appropriate position so that the transcranial ultrasound can be accurately focused on the target area.

[0004] To address the aforementioned issues, a navigation method and system suitable for transcranial ultrasound stimulation (TUS) is needed. This method and system integrates rapid transcranial sound field simulation calculations into the navigation system, thereby achieving high-spatial-precision navigation of TUS. First, because the skull deflects the direction of ultrasound propagation, it is impossible to directly determine the actual transcranial sound field focus position based on the relative position of the focus and the ultrasound transducer. Furthermore, because the sound pressure or intensity of low-intensity focused ultrasound within the skull is difficult to measure in real time during neuromodulation, it is impossible to use this real-time measurement data to provide feedback and guidance for adjusting the ultrasound transducer's position and orientation. One approach to addressing this challenge is to use skull imaging to detect structural information about brain tissue, such as the scalp and skull. Based on this brain tissue structure and acoustic properties, ultrasound propagation simulation calculations are then performed to determine the placement and orientation of the ultrasound transducer relative to the stimulation target.

[0005] After simulating the expected incident direction and position of the ultrasound transducer, a method is needed to guide the actual transducer to the desired location. Furthermore, because transcranial focused ultrasound is non-invasive, it cannot directly observe internal brain structures. Considering these requirements, a feasible navigation solution is frameless neuronavigation technology.

[0006] Navigation systems for neuromodulation technologies are primarily divided into two categories: MRI-guided navigation and optical navigation. MRI-based navigation systems offer high precision, but they require high-quality surgical equipment and are technically challenging to operate. Furthermore, the low-intensity focused ultrasound used for neuromodulation causes minimal temperature changes in brain tissue, making these subtle changes difficult to detect using MRI. Optical-based navigation systems offer ease of operation, low cost, and minimal environmental requirements, making them highly compatible with TUS.

[0007] Currently, TUS navigation schemes have also been proposed in the existing technology. However, these schemes do not take into account the fact that the actual focused ultrasound stimulation is actually forward propagating in the sound field simulation scheme. The technical scheme based on the time reversal method obtains that the focus of the ultrasound wave emitted by the ultrasound transducer at the placement position in the skull may still have a certain degree of spatial error with the target target; and these schemes also fail to provide visual sound field distribution information to guide the placement of the ultrasound transducer.

[0008] Therefore, there is an urgent need in this field to develop a real-time navigation method and system for ultrasound transducers for TUS, so as to effectively reduce the ultrasound focus position offset error caused by the skull and guide the placement of the ultrasound transducer, so that the focus of transcranial ultrasound can accurately fall on the predetermined stimulation target in the skull. Summary of the Invention

[0009] The purpose of this application is to provide a real-time navigation method and system for an ultrasonic transducer for transcranial ultrasound stimulation, which can effectively reduce the ultrasound focus position offset error caused by the skull, guide the placement of the ultrasound transducer, and allow the focus of the transcranial ultrasound to accurately fall on a predetermined target point in the skull.

[0010] The present application provides a real-time navigation method of an ultrasound transducer for transcranial ultrasound stimulation, comprising the following steps:

[0011] (a) Establish a computational model of the ultrasound sound field passing through the skull, pre-mark the intended stimulation targets within the skull based on skull morphology and stimulation requirements, and pre-determine the initial position and angle of the ultrasound transducer;

[0012] (b) placing a concave sound source representing a focused ultrasonic transducer based on the initial position and angle of the ultrasonic transducer, performing forward transcranial ultrasonic sound field simulation calculation, and thereby obtaining the position of a simulated acoustic focus (the simulated acoustic focus of the ultrasonic transducer) of the transcranial ultrasonic sound field generated by the ultrasonic transducer;

[0013] (c) calculating the distance between the ultrasonic transducer and the predetermined intracranial stimulation target at this time, and the distance between the ultrasonic transducer and the position of the simulated acoustic focus of the transcranial ultrasound sound field, and then using the gradient descent method to calculate the position and angle of the ultrasonic transducer in the intermediate rounds;

[0014] (d) placing a concave sound source representing a focused ultrasonic transducer based on the position and angle of the ultrasonic transducer in the intermediate round calculated in step (c), and performing a forward transcranial ultrasonic sound field simulation calculation to obtain a simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer in this round;

[0015] (e) Repeating iterative steps (c) and (d), and stopping the iteration when the iterative stopping condition is reached, thereby obtaining the optimal position and angle of the ultrasonic transducer for navigation; wherein the position and angle of the ultrasonic transducer used in each round of iterative calculation are obtained based on the results of the previous round of iterative calculation based on the gradient descent method.

[0016] In another preferred example, after obtaining the position and angle of the ultrasonic transducer in an intermediate round, a forward transcranial ultrasonic sound field simulation calculation is performed to obtain the simulated acoustic actual focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer at the position and angle of the ultrasonic transducer in the intermediate round.

[0017] In another preferred example, when using the gradient descent method to calculate the position and angle of the ultrasonic transducer for the next intermediate round, it is necessary to determine the gradient of the sound pressure field at the predetermined stimulation target point P0 obtained by performing forward ultrasonic sound field simulation calculation at the position and angle of the ultrasonic transducer in the previous intermediate round.

[0018] In another preferred example, considering that there may be multiple local minimum points or multiple local maximum points in the simulated sound field of transcranial ultrasound, the Gaussian smoothing filter algorithm is first used to smooth the transcranial ultrasound sound field obtained by simulation calculation, so that there are no local minimum points in the half-maximum full width area of the smoothed transcranial ultrasound sound field, and there are no local maximum points outside the maximum sound pressure value point. Then, when the gradient descent method is used to calculate the position and angle of the ultrasonic transducer in the next intermediate round, it is necessary to determine the gradient of the smoothed ultrasonic simulation sound field at the predetermined stimulation target point P0.

[0019] In another preferred example, step (c) also includes: before using the gradient descent method to calculate the position and angle of the ultrasonic transducer in the intermediate round, it includes a step of smoothing the transcranial ultrasonic sound field at this time obtained by the ultrasonic sound field simulation calculation, so that there is no local minimum point in the half-maximum full width area of the smoothed transcranial ultrasonic sound field, and there is no local maximum point outside the maximum sound pressure value point.

[0020] In another preferred example, the step of smoothing the transcranial ultrasonic sound field obtained by ultrasonic sound field simulation calculation occurs after calculating in step (c) the distance between the ultrasonic transducer and the predetermined stimulation target point in the skull and the distance between the ultrasonic transducer and the position of the simulated acoustic focus of the transcranial ultrasonic sound field.

[0021] In another preferred embodiment, the transcranial ultrasound sound field obtained by simulation calculation is smoothed by using a Gaussian smoothing filter algorithm, so that when the position and angle of the ultrasound transducer of the next intermediate round are calculated using the gradient descent method, it is necessary to determine the gradient of the smoothed transcranial ultrasound sound field at the predetermined stimulation target point P0.

[0022] In another preferred example, in step (b), a large number of point sound sources are set at various positions of the concave sound source, and the half-maximum full width area of the transcranial ultrasound sound field can be obtained by performing transcranial sound field simulation calculations, and the geometric center point or peak point of the area is used as the simulated acoustic focus of the transcranial ultrasound sound field generated by the ultrasonic transducer.

[0023] In another preferred embodiment, in step (c), in the first round of iterative calculation, the distance d between the ultrasonic transducer and the predetermined stimulation target in the brain is calculated by the following formula: 1,0 , and the distance d between the ultrasonic transducer and the position of the ultrasonic transducer simulated acoustic focus 1,b :

[0024] d 1,0 =|P0-P 1,a |;

[0025] d 1,b =|P 1,b-P 1,a |;

[0026] Among them, P0 is the location of the predetermined stimulation target in the brain, P 1,a is the initial position of the ultrasonic transducer, P 1,b The position of the transcranial simulated acoustic focus of the ultrasonic transducer obtained by the ultrasonic sound field simulation calculation in step (b).

[0027] In another preferred embodiment, in step (c), the gradient descent method is used to calculate the position and angle of the ultrasonic transducer in the intermediate rounds, including: in the first round of iterative calculation, by To calculate the angle and position of the ultrasonic transducer for the first intermediate round,

[0028] Angle of the ultrasonic transducer in the first intermediate round Determine according to the following calculation formula:

[0029]

[0030]

[0031] Where l is the set iteration step size;

[0032] The position P of the ultrasonic transducer in the first intermediate round 2,a Determine according to the following calculation formula:

[0033]

[0034] In another preferred embodiment, the iteration step length l is set according to the operator's experience, for example between.

[0035] In another preferred embodiment, the iteration stopping condition is: when the number of iteration rounds is greater than a preset iteration round number threshold N, the iteration is stopped.

[0036] In another preferred embodiment, the iteration stopping condition is: when the number of iteration rounds is n, P n,b When the distance error between P0 and P0 is less than a preset navigation space error threshold e, or when the decrease in the navigation space error value obtained in two adjacent iterations is less than a preset threshold, the iteration is stopped.

[0037] In another preferred embodiment, the specific iterative calculation formulas for the angle and position of the ultrasonic transducer in steps (c) and (d) are as follows:

[0038]

[0039]

[0040]

[0041] Where m=1,2,… is the number of iterations, P m,a is the position of the ultrasonic transducer in the mth round of transcranial ultrasound sound field simulation calculation, P m,b is the position of the simulated acoustic focus of the transcranial ultrasound sound field generated by the ultrasound transducer obtained in the mth round of transcranial ultrasound sound field simulation calculation, is the simulated sound field gradient of the transcranial ultrasound sound field at the predetermined stimulation target point P0 obtained by the mth round of sound field simulation calculation, is the angle of the ultrasonic transducer in the mth intermediate round, P m+1,a is the position of the ultrasonic transducer in the mth intermediate round.

[0042] In another preferred embodiment, It is the simulated sound field gradient of the smoothed transcranial ultrasound sound field at the predetermined stimulation target point P0 after smoothing the transcranial ultrasound sound field obtained by the mth round of sound field simulation calculation using the Gaussian smoothing filter algorithm.

[0043] In another preferred embodiment, the transcranial ultrasound sound field simulation calculation method adopts the k-space pseudospectral method.

[0044] In another preferred embodiment, the ultrasonic transducer is a single array ultrasonic transducer or an array composed of multiple element ultrasonic transducers.

[0045] In another preferred embodiment, step (a0) is further included before step (a): preprocessing the image data of the subject's head to obtain a structural model of the subject's head and sound field simulation medium data, wherein the sound field simulation medium data is used to establish a sound field calculation model of ultrasound passing through the skull.

[0046] In another preferred example, the method also includes a registration and alignment step, which converts the position and angle of the optimal ultrasonic transducer of the head in the real coordinate system into the corresponding position and angle of the head structure model in the image coordinate system of the graphical interface based on the subject's head structure model, thereby guiding the ultrasonic transducer in the real coordinate system to the specified position in the image coordinate system of the graphical interface.

[0047] In another preferred example, the registration and alignment step also includes selecting corresponding points of human facial feature points in the image coordinate system on the subject's head structure model to form a pairing point set, and using a rigid body to obtain the positions of the human facial feature points selected in the image coordinate system in the real coordinate system.

[0048] In another preferred embodiment, the number of facial feature points of the human body is 3 or more.

[0049] In another preferred embodiment, the facial feature points are selected from the following group: the outer end of the eye socket, the distal end of the ear, the root of the earlobe, the tip of the nose, the root of the nose, or the corner of the lip.

[0050] In another preferred embodiment, the registration and alignment step implements registration and alignment by performing pairing calculations on feature points using a singular value decomposition method.

[0051] In another preferred example, assuming that the real coordinate system is a first rigid system and the image coordinate system is a second rigid system, the real coordinate system and the image coordinate system are transformed through rotation and translation, thereby obtaining the transformation relationship between the real coordinate system and the image coordinate system, and then obtaining the corresponding position of any point on the real coordinate system on the image coordinate system.

[0052] In another preferred embodiment, the registration and alignment step occurs before, after, or simultaneously with the sound field simulation calculation step; to avoid the subject waiting, the registration and alignment step may be performed after the sound field simulation calculation step.

[0053] The present application also provides a real-time navigation system for an ultrasound transducer for transcranial ultrasound stimulation, comprising:

[0054] An image preprocessing module, configured to preprocess image data of the subject's skull to obtain a structural model of the subject's skull and sound field simulation medium data;

[0055] an acoustic field simulation calculation module configured to establish an ultrasonic acoustic field simulation calculation model based on the acoustic field simulation medium data, adjust the position and angle of the transducer by a gradient descent method, and perform acoustic field calculations to obtain an optimal ultrasonic transducer orientation and position;

[0056] The registration and alignment module is configured to convert the position and angle of the optimal ultrasound transducer of the skull in the real coordinate system and the corresponding position and angle in the skull structure model in the image coordinate system based on the subject's skull structure model.

[0057] In another preferred example, the system further includes a space tracking and positioning device, which is configured to utilize an infrared optical tracking and positioning device to obtain coordinate data of the positioning rigid body in a real space coordinate system.

[0058] In another preferred example, the spatial tracking and positioning device includes a first rigid body, a second rigid body and a third rigid body. The first rigid body points to a feature point on the surface of the skull in the real space coordinate system, and is used to obtain the coordinate data of the feature point in the real coordinate system during registration and alignment. The second rigid body is bound to the ultrasonic transducer and is calibrated with the ultrasonic transducer to obtain the coordinate data of the ultrasonic transducer in the real coordinate system. The third rigid body is bound to the subject's head to obtain the coordinate data of the head in the real coordinate system to track the spatial position of the head.

[0059] In another preferred example, the system further includes a device communication module, which is configured to obtain the position and angle data of the first rigid body, the second rigid body and the third rigid body in the real coordinate system in real time, and pass the obtained data to the registration and alignment module.

[0060] In another preferred example, the system further comprises a real-time navigation module, which is configured to display the specific position and angle of the ultrasonic transducer in the image coordinate system in real time and guide the ultrasonic transducer to an optimal position and angle.

[0061] In another preferred example, the image preprocessing module is also configured to visually display a three-dimensional model of the skull, and to display the relative position and angular relationship between the ultrasonic transducer and the predetermined stimulation target in the skull and the expected (optimal) ultrasonic transducer position, and to superimpose the transcranial ultrasonic sound field distribution generated by the ultrasonic transducer at the expected (optimal) ultrasonic transducer position and angle on the skull structure model in real time.

[0062] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. It should be understood that the drawings described below are merely some implementation examples of the present invention, and those skilled in the art can also derive other implementation examples based on these drawings without inventive effort.

[0064] Figure 1 is a structural block diagram of a real-time navigation system of an ultrasound transducer for transcranial ultrasound stimulation according to one embodiment of the present application;

[0065] Figure 2This is a schematic diagram of guiding an ultrasonic transducer to a specified position through a graphical interface after registration and alignment according to one embodiment of the present application;

[0066] Figure 3 Schematic diagram of an iterative algorithm for finding the optimal incident position and orientation of an ultrasonic transducer based on the principle of gradient descent according to one embodiment of the present application (where a: initial position and angle of the ultrasonic transducer; b and c: intermediate stages of the iterative algorithm based on gradient descent; d: termination condition of the iterative algorithm);

[0067] Figure 4 The figure is a flow chart of a real-time navigation method of an ultrasound transducer for transcranial ultrasound stimulation according to one embodiment of the present application.

[0068] In the accompanying drawings, the symbols are as follows:

[0069] 1-Ultrasonic transducer

[0070] 2-Spatial tracking and positioning equipment

[0071] 3-First rigid body (pointer rigid body)

[0072] 4-Second rigid body (transducer rigid body)

[0073] 5-The third rigid body (head moving rigid body) DETAILED DESCRIPTION

[0074] Through extensive and in-depth research, the inventors have developed for the first time a real-time navigation method and system for ultrasonic transducers for transcranial ultrasonic stimulation. The real-time navigation system and method of the present application can find the optimal placement position and orientation of an array composed of a single-element ultrasonic transducer or a multi-element ultrasonic transducer through transcranial ultrasonic sound field simulation, and through registration and alignment, the position and angle of the optimal ultrasonic transducer of the head in the real coordinate system and the corresponding position and angle in the head structure model in the image coordinate system are converted to each other, so that the ultrasonic transducer in the real coordinate system can be guided to the specified position in the image coordinate system of the graphical interface, thereby realizing that the ultrasonic waves emitted by the ultrasonic transducer or transducer array are accurately focused on the pre-planned stimulation target in the skull after passing through the skull and other brain tissues.

[0075] the term

[0076] As used herein, “orientation of the ultrasonic transducer” and “angle of the ultrasonic transducer” are used interchangeably;

[0077] As used herein, “predetermined stimulation target,” “predetermined stimulation target,” “intracranial predetermined stimulation target,” and “target target” are used interchangeably;

[0078] As used in this article, the "simulated acoustic focus of the transcranial ultrasound sound field" is the "simulated acoustic focus of the transcranial ultrasound sound field generated by the ultrasonic transducer", which can be called the "simulated acoustic focus of the ultrasonic transducer" or the "transcranial simulated acoustic focus of the ultrasonic transducer".

[0079] Transcranial ultrasound stimulation

[0080] Transcranial Ultrasound Stimulation (TUS) is a non-invasive functional neuromodulation technology that has developed rapidly in recent years. It regulates (enhances or inhibits) brain neural activity by transmitting low-frequency, low-intensity pulsed ultrasound waves through brain tissue such as the scalp and skull.

[0081] Neuronavigation technology

[0082] Neuronavigation technology, also known as image-guided neurosurgery (IGNS), is a technique that uses preoperative imaging data such as computed tomography (CT) and magnetic resonance imaging (MRI) to establish an image-guided space. It uses optical or other tracking devices to track and display the position of surgical instruments relative to brain tissue and lesions in real time, thereby guiding doctors during surgical operations.

[0083] Ultrasonic transducer:

[0084] Ultrasonic transducers can convert electrical energy into mechanical (acoustic) energy and vice versa based on the piezoelectric effect. They can generate ultrasonic waves as well as receive and detect them. They are generally composed of five main components: a crystal / ceramic element with piezoelectric properties, a positive electrode and a ground electrode on the surface of the element, a damping (backing) block, a matching layer, and a housing.

[0085] Registration:

[0086] Image registration is the process of converting data from different sources into a single coordinate system. The data may come from different sensors, at different times, at different depths, and at different viewpoints. It is commonly used in computer vision, medical imaging, and automated target recognition in the military. Registration is essential for comparing and integrating data obtained from different measurement methods.

[0087] The terms "comprise," "include," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, article, or apparatus comprising a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus. Without further limitation, the phrase "comprising an element" does not preclude the presence of additional identical elements in the process, method, article, or apparatus comprising the element. Throughout this patent application, reference to performing an action in accordance with an element means performing the action in accordance with at least that element, including two situations: performing the action in accordance with only that element and performing the action in accordance with that element and other elements. Expressions such as "plurality," "multiple times," and "many" include "two," "twice," "two kinds," and more than two, "more than two times," and more than two kinds. It should be noted that, throughout this patent application, relational terms such as "first and second," etc., are used solely to distinguish one entity or operation from another and do not necessarily require or imply any actual relationship or order between these entities or operations.

[0088] In the present invention, all directional indications (such as up, down, left, right, front, back, etc.) are only used to explain the relative position relationship, movement status, etc. between the various components under a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0089] The main advantages of the present invention are:

[0090] (a) The present invention discloses a real-time navigation method and system for an ultrasonic transducer for transcranial ultrasound stimulation. The method and system perform iterative simulation of the transcranial ultrasound sound field based on the gradient descent principle to find the optimal placement and orientation of the ultrasonic transducer for transcranial ultrasound stimulation. This method can effectively reduce the offset error of the transcranial ultrasound focus position caused by the skull, guide the placement of the ultrasonic transducer, and allow the focus of the transcranial ultrasound to accurately fall on the preset stimulation target in the skull. The system also provides visual sound field distribution information to guide the placement of the ultrasonic transducer.

[0091] (b) In the real-time navigation method and system for an ultrasonic transducer for transcranial ultrasound stimulation of the present application, various approaches can be used to set the initial position and orientation of the ultrasonic transducer at the scalp according to the needs of use. Then, the actual focus and sound field data of the ultrasonic transducer at this time are obtained through forward transcranial sound field simulation. In combination with the relationship between the sound field focus and the target point, the next placement position and orientation of the ultrasonic transducer are calculated based on the principle of gradient descent. Then, the next round of forward transcranial sound field simulation calculation is performed, and the iteration is continued until the termination condition is met to obtain the desired (optimal) position and orientation of the ultrasonic transducer.

[0092] (c) Existing navigation technologies do not consider the impact of brain tissue, such as the skull, on transcranial ultrasound propagation, or use other methods to determine the position and orientation of the ultrasound transducer for navigation. This results in a certain degree of spatial error and fails to provide navigation guided by forward transcranial sound field distribution information. The present invention performs forward transcranial ultrasound sound field calculations, performs forward iterative sound field simulation calculations based on the principle of gradient descent, and continuously corrects the position and orientation of the ultrasound transducer. Ultimately, the spatial position error between the acoustic focus of the ultrasound wave emitted by the ultrasound transducer after propagation through the skull and the predetermined stimulation target is minimized, thereby achieving transcranial ultrasound stimulation navigation with high spatial precision.

[0093] (d) The real-time navigation method and system of an ultrasonic transducer for transcranial ultrasound stimulation of the present application obtains the positions of multiple anatomical feature points of the head in the image coordinate system and the real coordinate system through software interaction and an optical tracking device (spatial tracking and positioning device), obtains paired point sets in the two coordinate systems, calculates the rotation matrix and vector between the two point sets using singular value decomposition, and obtains the transformation relationship between the two coordinate systems, which is used to display the position of the ultrasonic transducer in the image coordinate system on the software graphical interface;

[0094] (e) The navigation system in this application uses singular value decomposition to solve the rigid body rotation and translation matrix for registration. Compared with the existing technology, the registration method proposed in this application reduces the influence of noise and the operational error when obtaining the coordinates of the paired points by increasing the number of paired points involved in the registration, thereby achieving high-precision registration, thereby obtaining higher-precision transcranial ultrasound stimulation navigation;

[0095] (f) The TUS navigation method designed in this application will strongly promote the development and application of TUS, provide a new tool for TUS-based brain science research and clinical treatment of brain diseases, and give full play to the high spatial precision advantage of TUS.

[0096] In the following description, many technical details are provided to help readers better understand this application. However, those skilled in the art will understand that even without these technical details and various changes and modifications based on the following embodiments, the technical solutions claimed in this application can be implemented.

[0097] Real-time navigation method of ultrasound transducer for transcranial ultrasound stimulation

[0098] The present application provides a real-time navigation method of an ultrasound transducer for transcranial ultrasound stimulation, the method comprising the following steps:

[0099] (a0) Preprocessing the image data of the subject's head to obtain the subject's head structure model and sound field simulation medium data;

[0100] (a) Establishing a computational model of the ultrasound field passing through the skull based on the acoustic field simulation medium data, and determining the initial position and angle of the ultrasound transducer based on the predetermined stimulation target within the skull;

[0101] (b) placing a concave sound source representing a focused ultrasonic transducer based on the initial position and angle of the ultrasonic transducer, performing forward transcranial ultrasonic sound field simulation calculation, and thereby obtaining the position of the simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer;

[0102] (c) calculating the distance between the ultrasonic transducer and the predetermined intracranial stimulation target at this time, and the distance between the ultrasonic transducer and the position of the simulated acoustic focus of the transcranial ultrasound sound field, and then calculating the position and angle of the ultrasonic transducer in the intermediate rounds using a gradient descent method;

[0103] (d) performing a forward transcranial ultrasound sound field simulation calculation based on the position and angle of the ultrasound transducer in the intermediate rounds calculated in step (c), thereby obtaining a simulated acoustic focus of the transcranial ultrasound sound field generated by the new ultrasound transducer;

[0104] (e) Repeating iterative steps (c) and (d), and stopping the iteration when the iterative stopping condition is reached, thereby obtaining the optimal position and angle of the ultrasonic transducer for navigation; wherein the position and angle of the ultrasonic transducer used in each round of iterative calculation are obtained based on the results of the previous round of iterative calculation based on the gradient descent method.

[0105] In which, in step (b), a large number of point sound sources are set at various positions of the concave sound source representing the ultrasonic transducer. After performing sound field simulation calculations, the half-maximum full width area of the transcranial ultrasonic sound field can be obtained, and the geometric center point of the area is used as the simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer; the peak point of the half-maximum full width area can also be used as the simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer.

[0106] In addition, in step (c), considering that the simulated sound field of transcranial ultrasound may have multiple local minimum points or multiple local maximum points, the Gaussian smoothing filter algorithm is first used to smooth the simulated transcranial ultrasound sound field, so that there are no local minimum points in the half-maximum full width area of the smoothed transcranial ultrasound sound field, and there are no local maximum points outside the maximum sound pressure value point. Then, when the gradient descent method is used to calculate the position and angle of the ultrasonic transducer in the next intermediate round, it is necessary to determine the gradient of the smoothed ultrasonic simulated sound field at the predetermined stimulation target point P0.

[0107] In other words, step (c) also includes: before using the gradient descent method to calculate the position and angle of the ultrasonic transducer in the intermediate round, and after calculating the distance between the ultrasonic transducer and the predetermined intracranial stimulation target and the distance between the ultrasonic transducer and the position of the ultrasonic transducer simulation acoustic focus in step (c), it includes a step of smoothing the transcranial ultrasonic sound field obtained by the ultrasonic sound field simulation calculation at this time, so that there is no local minimum point in the half-maximum full width area of the smoothed transcranial ultrasonic sound field, and there is no local maximum point outside the maximum sound pressure value point.

[0108] Preferably, the transcranial ultrasound sound field obtained by simulation calculation is smoothed by using a Gaussian smoothing filter algorithm, so that when the position and angle of the ultrasound transducer are calculated in the next intermediate round using the gradient descent method, the gradient of the smoothed transcranial ultrasound sound field at the predetermined stimulation target point P0 needs to be determined. It should be noted that in each iteration, before using the gradient descent method to calculate the position and angle of the ultrasonic transducer in the intermediate round, it is necessary to smooth the transcranial ultrasonic sound field obtained by the ultrasonic sound field simulation at this time, so that there are no local minimum points in the half-maximum full width area of the smoothed transcranial ultrasonic sound field, and there are no local maximum points outside the maximum sound pressure value point. Then, when using the gradient descent method to calculate the position and angle of the ultrasonic transducer in the next intermediate round, it is necessary to determine the gradient of the smoothed ultrasonic simulation sound field at the predetermined stimulation target point P0.

[0109] The method also includes a registration and alignment step, which converts the position and angle of the optimal ultrasonic transducer of the head in the real coordinate system into the corresponding position and angle of the head structure model in the image coordinate system based on the subject's head structure model, thereby guiding the ultrasonic transducer in the real coordinate system to the specified position in the image coordinate system of the graphical interface.

[0110] The registration and alignment step also includes selecting corresponding points of human facial feature points in the image coordinate system on the subject's head structure model to form a pairing point set, and using a rigid body to obtain the positions of the human facial feature points selected in the image coordinate system in the real coordinate system.

[0111] The registration step pairs feature points using the singular value decomposition method. In one embodiment, assuming the real-world coordinate system is a first rigid system and the image coordinate system is a second rigid system, the real-world coordinate system and the image coordinate system are transformed through rotation and translation to derive the transformation relationship between the real-world coordinate system and the image coordinate system, thereby determining the corresponding position of any point in the real-world coordinate system in the image coordinate system. In one embodiment, the registration step occurs before, after, or simultaneously with the sound field simulation calculation step; to avoid waiting for the subject, the registration step can be performed after the sound field simulation calculation step.

[0112] The registration and alignment steps are implemented through the registration and alignment module, the spatial tracking and positioning device, and the device communication module.

[0113] Real-time navigation system of ultrasound transducers for transcranial ultrasound stimulation

[0114] like Figure 1 As shown, the present application also provides a real-time navigation system of an ultrasonic transducer for transcranial ultrasonic stimulation, including: an image preprocessing module, an acoustic field simulation calculation module, a spatial tracking and positioning device, a device communication module, a registration and alignment module, and a real-time navigation module.

[0115] Among them, the real-time navigation module provides real-time display of the specific position of the ultrasonic transducer in the image coordinate system and auxiliary instructions for guiding the ultrasonic transducer to the target position (predetermined stimulation target). The device communication module and the sound field simulation calculation module provide the navigation system with the coordinates of the ultrasonic transducer in the real coordinate system and the target position in the image coordinate system. The registration and alignment module provides the navigation system with the conversion relationship between the two coordinate systems. The image data preprocessing module realizes the function of three-dimensional visualization of the skull structure model, more intuitively showing the relative position relationship between the ultrasonic transducer and the preset target point in the skull and the target transducer position, and superimposing the distribution of the transcranial ultrasonic sound field generated by the ultrasonic transducer at the final determined ultrasonic transducer position and orientation on the skull structure model.

[0116] Image preprocessing module

[0117] The image preprocessing module first preprocesses the CT or MRI image data collected from the subject, and then constructs the skull structure model required in the registration and alignment module, as well as the sound field medium data required in the sound field simulation calculation module, from the image data. MRI has clearer imaging of soft tissues such as gray matter and white matter in the brain, while general structures such as MRI have weaker imaging signals for bone tissue; due to the strong ability of bone tissue to absorb radiation, CT imaging of bone tissue has obvious contrast compared to other tissues, and is the main way to obtain sound field simulation medium data. The present invention will mainly explain the preprocessing of CT image data, and the specific steps are as follows:

[0118] First, a CT scan of the subject's head is performed to obtain a x ×N y ×N z Three-dimensional image, pixel spacing is d x ×d y ×d z , while the 3D image data is Figure 2 The origin coordinate of the image coordinate system shown is o x ×o y ×oz The voxel with image index (i, j, k) is converted to coordinates (X, Y, Z) in the image coordinate system by the following formula:

[0119]

[0120] where i = 1, 2, ..., N x , j = 1, 2, ..., N y , k=1,2,...,N z . Then, the CT value threshold T of the skull is set, and the image pixel data is traversed. If the pixel intensity is greater than T, it will be retained, otherwise it will be removed, and finally three-dimensional data with only skull information is obtained. Since the porosity and density at different positions of the skull are different and it is not a uniform medium, the present invention uses the following empirical formulas (2), (3) and (4) of CT value, density and sound speed, and maps them to the image coordinate system through equation (1) to obtain the distribution of head sound speed and density at different positions of the image. The empirical formulas of CT value, density and sound speed are

[0121]

[0122] c (i，j，k) =c 水 ψ (i，j，k) +c 骨 (1-ψ (i，j，k) ), (3)

[0123] ρ (i，j，k) =ρ 水 ψ (i，j，k) +ρ 骨 (1-ψ (i，j，k) ), (4)

[0124] where H is the CT value indexed by (i, j, k) within the image range, ψ is the porosity, and c 水 and c 骨 is the speed of ultrasound in water and in the skull at that location, ρ 水 and ρ 骨 is the density of water and the density of the skull at that location.

[0125] Regarding image data processing: In this embodiment of the present invention, we primarily use CT image data of the skull as input to extract information about tissues such as the skull as parameters for the simulated sound field medium, which is then input into the simulation program. Equations (2)-(4) are used to convert CT values into medium density and sound velocity. In other embodiments, CT images of the skull can also be synthesized from magnetic resonance imaging (MRI) data of the skull. The synthesized CT images can then be used to extract information about tissues such as the skull as parameters for the simulated sound field medium, which is then input into the simulation program. There are also methods that directly use MRI images as input, segmenting the skull from the MRI images and obtaining representative values for skull density and sound velocity.

[0126] Sound field simulation calculation module

[0127] The sound field simulation calculation module is used to establish the ultrasonic sound field calculation model and determine the placement and orientation of the ultrasonic transducer. The specific steps are as follows: Figure 4 As shown. Step (1): Determine the initial position and orientation of the ultrasonic transducer. The present invention first processes the original image of the subject through the image preprocessing module to obtain the sound field parameter model, and then calibrates the pre-planned stimulation target (predetermined stimulation target) in the image space, and calibrates the position where the axis point of the ultrasonic transducer exit surface and the scalp contact are calibrated in the image space as the initial position of the ultrasonic transducer. The initial position can be determined and adjusted by a variety of methods as needed, such as by the operator based on experience, or by calculating the distance between the scalp and the target at each position and selecting the scalp position with the closest distance as the initial position of the ultrasonic transducer, or by finding a certain point on the scalp as the initial position of the ultrasonic transducer through calculation, and the skull section plane of the point is perpendicular to the line between the point and the target. After preliminarily setting the initial position of the ultrasonic transducer, the inward normal vector of the initial position on the skull surface is further calculated. If the angle between the line connecting the initial position and the target point and the normal vector is too large, then the preliminarily set position should not be used as the initial position of the ultrasonic transducer. The initial position should be further adjusted to make the angle smaller. This is because the ultrasonic wave is incident along the normal vector of the skull, and the skull has a small deflection on the propagation direction of the ultrasonic wave. The greater the deviation of the ultrasonic wave incident direction from the normal vector of the skull, the greater the deflection of the ultrasonic wave propagation direction caused by the skull. After adjusting and determining the initial position of the ultrasonic transducer, the direction of the line connecting the position to the target point is used as the initial orientation of the central axis of the ultrasonic transducer.

[0128] Step (2): Perform sound field calculation and adjust the orientation and position of the ultrasonic transducer based on the gradient descent method proposed in the present invention. According to the specific size and structural design of the ultrasonic transducer used, a concave sound source is set for simulation calculation. The position and orientation of the concave sound source are set according to the initial position and orientation of the ultrasonic transducer determined in step (1). It should be noted that the concave sound source is composed of multiple point sound sources with the same ultrasonic sound source emission parameters. After forward transcranial propagation, these point sound sources obtain the simulated acoustic focus of the entire concave sound source. After the spatial position of this focus is compared with the target point, the gradient descent method proposed in the present invention is used to adjust the orientation and position of the ultrasonic transducer to reduce the spatial error between the focus of the concave sound source representing the ultrasonic transducer and the pre-set stimulation target point. After each round of transcranial sound field calculation in the present invention, the gradient descent method is used to adjust the orientation and position of the ultrasonic transducer, and then the next round of transcranial sound field calculation is performed according to the adjusted orientation and position, and the gradient descent method is used to further adjust the orientation of the ultrasonic transducer according to the new transcranial sound field calculation result. This iterative calculation cycle is repeated multiple times, with the orientation and position adjustments repeated until the spatial distance between the calculated transcranial sound field focus and the pre-set target point after a certain orientation adjustment is less than a user-defined acceptable threshold, or the number of iterations reaches a user-defined threshold. The iterative calculation is then terminated, and the position and orientation of the ultrasonic transducer at the last adjustment is the position and orientation determined by the present invention. If there is a certain distance between the position of the ultrasonic transducer calculated using this method and the scalp, an ultrasonic coupling medium (such as a degassing water bag, a specially formulated gel pad, etc.) may need to be placed between the ultrasonic transducer and the scalp.

[0129] The principle behind the gradient descent method proposed in this paper is to iteratively search in the opposite direction of the gradient or approximate gradient corresponding to the current point in the simulated transcranial ultrasound sound field distribution, until the local minimum of the function is reached. Specifically, the objective function to be optimized is the distance from the simulated transcranial sound field focal point to the target point. The gradient direction of the target point in the simulated transcranial ultrasound sound field is used as the adjustment direction of the ultrasonic transducer, and the position and orientation of the ultrasonic transducer are updated with a given step size.

[0130] Ultrasonic sound field simulation calculation method

[0131] The ultrasound field simulation calculation described in the present invention can be performed by assuming that ultrasound propagates linearly throughout the entire sound field, in order to simplify the simulation steps and computational complexity, reduce the computer memory requirements for the simulation calculation, and maintain the accuracy of the ultrasound simulation results. Furthermore, due to the low frequency of transcranial focused ultrasound, the nonlinear attenuation factor in the sound field can be ignored. Furthermore, to reduce the spatial resolution requirements for the original image data and increase the simulation calculation speed, the present invention uses the pseudo-spectral k-space (k-Space) method for simulation calculation. The calculation steps of this method are as follows:

[0132] For a uniform, lossless fluid medium, the linear acoustic wave equation can be derived from the following three equations:

[0133]

[0134]

[0135]

[0136] Where u is the acoustic particle velocity, p is the acoustic pressure, ρ is the acoustic density, c0 is the speed of sound, and ρ0 is the net field density. This equation assumes that there is no relaxation mechanism in a thermoviscous fluid. Combining the above formulas yields the second-order wave equation

[0137]

[0138] However, for the convenience of calculation and subsequent error elimination, the sound field simulation of the present invention will be calculated using the above-mentioned first-order equations (5), (6) and (7) instead of the more familiar second-order wave equation (8).

[0139] If it is assumed that there is absorption of sound waves and the situation is non-homogeneous, it is necessary to further add correction terms to equations (6) and (7) to obtain

[0140]

[0141]

[0142] Where d is the particle displacement and L is the linear integral differential operator for calculating sound absorption and scattering.

[0143] The above formula describes how the sound field propagates. By adding initial conditions, we can describe how sound waves are generated in the medium.

[0144]

[0145]

[0146] Among them S F is the initial external force source, S M is the initial mass input source.

[0147] The present invention introduces a pseudo-spectral k-space method to solve partial differential equations. With this method, the partial differentials in the wave equation can be calculated by the Fourier equation, rather than by the traditional finite difference approximation, to avoid large linear phase errors. At the same time, the pseudo-spectral k-space method can be regarded as the limit case of the infinite-order accurate finite difference method. In theory, only two nodes per wavelength are needed to obtain accurate and smoothly varying coefficients. For a general second-order wave equation, its specific form is

[0148]

[0149] in is the scalar wave number.

[0150] For the general three-dimensional discretized k-space method, calculation can be performed using the following equation.

[0151]

[0152]

[0153]

[0154]

[0155]

[0156] Wherein, equations (14) and (16) represent the gradient calculation formula based on the pseudospectral k-space method, and equations (15), (17), and (18) are the first-order accurate forward differences of equations (11), (12), and (10) in the case of continuous variables after k-space correction; ξ = x, y, z are the coordinate axis directions of the three-dimensional linear space; n and n + 1 are the current time and the next time of the corresponding variable; and They are Fourier transform and inverse Fourier transform, which can be solved by fast Fourier transform; Δt is the time interval; is the k-space operator, c ref is the background sound speed; k ξ Represents the wave number in the ξ direction, and the discrete form is as follows

[0157]

[0158] Among them, N ξ is the number of grids in the ξ direction; L d is the discrete form of power-law absorption, and the specific formula is

[0159]

[0160] in represent the absorption and scattering proportional coefficients respectively, α0 is the power law pre-coefficient, and y is the power law exponent.

[0161] At the same time, the sound intensity of the entire sound field can be calculated by combining the following formula

[0162]

[0163] In order for the discrete simulation to be accurate, the convergence condition needs to be maintained The CFL number is

[0164] Finally, the pseudo-spectral k-space method introduces a perfect matching layer (PML) to absorb sound waves outside the simulation range. Sound waves propagating at the boundary are sharply attenuated and not reflected, preventing the oscillation effect of the Fourier space transform at the boundary from affecting the simulation results. The pseudo-spectral k-space method iteratively calculates the sound pressure gradient of the sound field to determine the sound velocity distribution at the next moment, and then calculates the sound velocity gradient to determine the sound pressure distribution at the next moment, ultimately completing the entire simulation process.

[0165] According to the above simulation formula, after the structural information of the ultrasonic transducer and the sound propagation medium information are given, the forward propagation simulation calculation of the concave sound source of the ultrasonic transducer can be performed.

[0166] It should be noted that compared with other calculation methods, the k-space pseudospectral method has advantages in calculation accuracy and speed.

[0167] Adjust the orientation (angle) and position of the ultrasonic transducer based on the gradient descent method

[0168] Based on the above sound field calculation, the steps of the gradient descent method for determining the orientation and position of the ultrasonic transducer proposed in the present invention are as follows: Figure 3 and Figure 4 The specific simulation steps are as follows:

[0169] Step (1): The specific position of the preset transcranial ultrasound stimulation target point P0 can be expressed as (x0, y0, z0), such as Figure 3 First, the medium information of the sound field simulation, such as the sound velocity, density, shape and boundary of the medium, which has been converted from the original image data in the image preprocessing module, is input as the simulation parameter. The initial position P of the ultrasonic transducer is determined according to the method described above. 1,a and the initial direction of the central axis of the ultrasonic transducer The normal vector on the skull surface is calculated at this initial position to determine the rationality of the initial placement and orientation. The normal vector can be calculated by performing a K-nearest neighbor search on the location point, constructing a covariance matrix for the neighboring points, and solving for the eigenvectors and eigenvalues of the covariance matrix. The eigenvector corresponding to the minimum eigenvalue is the normal vector.

[0170] Step (2): To simulate the forward propagation of the ultrasonic transducer, it is necessary to 1,a Set as Figure 3 The concave sound source of the ultrasonic transducer shown in the figure has a curvature radius of the concave surface and a transducer aperture of . At the same time, the position and orientation of the concave sound source have been determined by step (1). A large number of point sound sources are set at various positions on the surface of the concave sound source, and the input of the external sound source is set in the sound field. The equation for the change of sound pressure at the point sound source with time is:

[0171] p source =A·sin(2πft), (22

[0172] Where A is the ultrasonic sound intensity amplitude, f is the ultrasonic oscillation frequency, and t is the moment of ultrasonic emission.

[0173] Afterwards, the transcranial sound pressure distribution of the ultrasonic transducer placed at the current position can be obtained by performing forward sound field simulation calculations. The actual sound field at the focus after the concave sound source propagates through the skull is a long ellipsoid with the long axis in the direction of sound field propagation. For the convenience of subsequent calculations, the center of the half-height full width area is taken as the focus point P 1,b .

[0174] For a concave single-element transducer, its focal length in a free sound field is a fixed value. In other words, if there is a large difference between the distance from the actual focus to the concave sound source and the distance from the target point to the concave sound source, simply adjusting the orientation of the ultrasonic transducer will not make the target point coincide with the actual focus. The distance from the ultrasonic transducer to the scalp must also be adjusted. First, calculate the distance d between the target point and the ultrasonic transducer placement position at this time. 1，0 =|P0-P 1，a |And the distance d between the transcranial simulation sound field focus and the ultrasound transducer 1，b =|P 1，b -P 1，a |.

[0175] Step (3): Determine the gradient of the sound pressure field calculated by the forward transcranial sound field simulation at the target point P0 as The present invention adopts a gradient descent strategy to adjust the orientation of the ultrasonic transducer, so that the orientation of the ultrasonic transducer is adjusted according to the gradient direction, such as Figure 3 As shown in (b). Let vector The target focus position of the next round of sound field simulation calculation determined by the gradient descent strategy of the present invention is Where l is the set iteration step. In the next round of transcranial sound field simulation calculation, the direction of the ultrasonic transducer is calculated according to the vector to set.

[0176] Step (4): Use the distance d calculated in step (2) 1，0 and d 1，b To update the position of the ultrasound transducer in the next round of transcranial sound field simulation calculation After the orientation and position of the ultrasonic transducer are updated, the next round of forward transcranial sound field simulation calculation is shown in the figure below: Figure 3 As shown in (c), the transcranial sound field focus at this time can be calculated as P 2，b .

[0177] The present invention then iterates and iterates the sound field calculation according to steps (2) to (4). The specific iterative calculation equation is as follows:

[0178]

[0179]

[0180]

[0181]

[0182] Where m = 1, 2, ..., is the number of iterations, P m，a is the position of the ultrasonic transducer in the mth round of transcranial sound field simulation calculation, P m，b is the focal position of the transcranial ultrasound sound field obtained in the mth round of transcranial sound field simulation calculation, P m，c is the target focal position of the m+1th round of sound field simulation calculation determined by the gradient descent strategy based on the sound field obtained in the mth round of transcranial sound field simulation calculation, It is the sound field gradient at the target point obtained by the mth round of sound field simulation. The present invention continuously iteratively adjusts the orientation and position of the ultrasonic transducer according to the above iterative equation, performs forward propagation simulation, obtains the sound field distribution of the next round of transcranial ultrasonic transducer, and stops the iterative calculation when the iterative stop condition is reached. The orientation and position of the ultrasonic transducer obtained at this time are used to guide the navigation system to place the ultrasonic transducer in the target orientation and position. The iterative stop condition can be set in different ways according to needs, such as when the number of iterations is greater than the preset iteration threshold N, or when the number of iterations is n, P n，b When the distance error between P0 and P0 is less than the preset navigation space error threshold e, or when the decrease in the navigation space error value obtained by two adjacent iterations is less than a preset threshold, Figure 3 As shown in (d).

[0183] Preferably, considering that the simulated sound field of transcranial ultrasound may have multiple local minimum points or multiple local maximum points, It is the simulated sound field gradient of the smoothed transcranial ultrasound sound field at the predetermined stimulation target point P0 after smoothing the transcranial ultrasound sound field obtained by the mth round of sound field simulation calculation using the Gaussian smoothing filter algorithm, wherein there is no local minimum point in the half-maximum full width area of the smoothed transcranial ultrasound sound field, and there is no local maximum point outside the maximum sound pressure value point.

[0184] Space tracking and positioning equipment

[0185] The spatial tracking and positioning device 2 is a device that determines the target position in real time by tracking the position of an active or passive infrared marker attached to the target, and the position of the infrared reflective marker is determined by a spatial tracking and positioning device 2 (such as a camera system) ( Figure 2 ). The spatial tracking and positioning device in this embodiment uses the PolarisVicra infrared optical positioning device of Canada NDI Company. Figure 2 The first rigid body 3 and Figure 2 As shown in the second rigid body 4 and the third rigid body 5. The first rigid body 3 is calibrated by rotation to determine the relative distance between the needle tip and the rigid body body, thereby obtaining the position in the real coordinate system. The specific operation is: insert the needle tip of the first rigid body 3 into a circular hole groove, and then rotate the first rigid body 3 around the circular hole, while continuously obtaining the rigid body transformation matrix of the tool coordinate system of the first rigid body 3 relative to the real coordinate system. Since the position of the needle tip in the real coordinate system and the tool coordinate system does not change, the position of the tool coordinate system relative to the real coordinate system will continue to change due to the continuous rotation of the first rigid body 3. Specifically, it is distributed on the surface of a sphere with the needle tip as the center of the sphere and the radius as the distance from the origin of the tool coordinate system to the needle tip in the real coordinate system. According to the above relationship, the relevant equations can be obtained, and the position of the needle tip in the tool coordinate system of the first rigid body 3 is solved to determine the coordinates of the needle tip in the tool coordinate system.

[0186] In this embodiment, the coordinates of the ultrasonic transducer 1 in the tool coordinate system of the second rigid body 4 can also be set to determine the position and orientation of the ultrasonic transducer.

[0187] From the above, it can be seen that the spatial tracking and positioning device may include a first rigid body 3, a second rigid body 4 and a third rigid body 5. The needle tip of the first rigid body 3 points to a feature point on the surface of the skull in the real coordinate system, and is used to obtain the coordinate data of the feature point in the real coordinate system during registration and alignment. The second rigid body 4 is bound to the ultrasonic transducer 1 and is calibrated with the ultrasonic transducer 1 to obtain the coordinate data of the ultrasonic transducer in the real coordinate system. The third rigid body 5 is bound to the subject's head to obtain the coordinate data of the head in the real coordinate system to track the spatial position of the head.

[0188] Device communication module

[0189] The device communication module uses the connection between the spatial tracking and positioning device and the computer, such as a universal serial port, wired network cable or wireless network, and the API interface of the software development kit provided by the device manufacturer to obtain the position and orientation of rigid bodies 3, 4 and 5 in the real coordinate system in real time, and pass the obtained data to the registration and alignment module.

[0190] Registration and registration module and registration and registration method steps

[0191] The registration module provides an interactive image interface for selecting corresponding points in the image coordinate system and the real coordinate system, as well as a registration algorithm between paired points. This embodiment uses the anatomical feature paired point registration method. Specifically, the user needs to use the mouse to select human facial features such as the outer end of the eye socket, the distal end of the ear, the tip of the nose, the root of the nose, the corner of the lip, etc. on the interactive interface containing the three-dimensional skull model reconstructed by the image preprocessing module, and form a paired point set {d i}, then use the tip of the first rigid body to select the corresponding position of each feature point selected in the image coordinate system in the real coordinate system, and communicate with the spatial positioning tracking device through the device communication module to obtain the paired point set {s i} in the real coordinate system. At least four pairs of such paired points are selected, and they are not on the same plane. In this implementation case, it is better to select five pairs or more. After obtaining the positions of the paired point set in the image coordinate system and the real coordinate system respectively, the implementation case uses the singular value decomposition method to align the paired points. Specifically, assuming that the two coordinate systems are rigid systems, the two coordinate systems can be transformed into each other through rotation and translation. The coordinates of the paired point set in the real coordinate system {s i} and the coordinates {d i}The following conversion relationship exists

[0192] d i =Rs i +D, (27)

[0193] Where R is the rotation matrix and D is the displacement vector. R and D can be solved by the following steps:

[0194] Step (1): First, find the centroid of the two point clouds respectively

[0195]

[0196]

[0197] Step (2): Find the displacement vector of each point relative to the center of mass, i.e. d′ i =d i -d,s′ i =s i -s.

[0198] Step (3): Calculate the H matrix using the centroid displacement vector

[0199]

[0200] Step (4): Perform SVD decomposition on the H matrix

[0201] H=UΛV T . (31)

[0202] Step (5): Based on matrices U and V, calculate the rotation matrix R

[0203] R=VU T . (32)

[0204] Step (6): Calculate det(R). If det(R) = 1, the result is retained, otherwise the registration step should be repeated. i} and {s i}When the distribution is not on a plane and the error is small, der(R) < 0 will not occur.

[0205] Step (7): Finally calculate the displacement vector D between the two point sets

[0206] D=d-Rs. (33)

[0207] At this point, the transformation relationship between the two coordinate systems is derived. Using this transformation relationship, the corresponding position of any point in the real-world coordinate system in the image coordinate system can be obtained. This allows the coordinates of the second rigid body to be displayed in the image-based coordinate system graphical interface of the real-time navigation module, indicating the ultrasonic transducer position and guiding the system to the desired ultrasonic transducer position.

[0208] Real-time navigation module

[0209] The real-time navigation module provides real-time display of the specific position of the ultrasonic transducer in the image coordinate system and auxiliary instructions for guiding the ultrasonic transducer to the expected position and orientation obtained by iterative calculation based on the gradient descent method.

[0210] The real-time navigation module obtains the coordinates of the second and third rigid bodies in the spatial tracking and positioning device in the real-world coordinate system through the device communication module. It then uses the rigid body transformation matrix obtained by the registration module to obtain the coordinates of these rigid bodies in the image coordinate system, thereby indicating the coordinates of the ultrasonic transducer and the skull in the image coordinate system. By transforming the actual position and angle of the ultrasonic transducer, it is ensured that its position and angle in the image coordinate system coincide with the expected (optimal) position and angle of the ultrasonic transducer, calculated iteratively using the gradient descent method.

[0211] All documents mentioned in this application are considered to be included in their entirety in the disclosure of this application so that they can be used as a basis for modification when necessary. In addition, it should be understood that after reading the above disclosure of this application, those skilled in the art may make various changes or modifications to this application, and these equivalent forms also fall within the scope of protection claimed in this application.

Claims

1. A real-time navigation method for an ultrasound transducer for transcranial ultrasound stimulation, characterized in that: The following steps are involved: (a) Establish a computational model of the ultrasound sound field passing through the skull, pre-mark the intended stimulation targets within the skull based on skull morphology and stimulation requirements, and pre-determine the initial position and angle of the ultrasound transducer; (b) placing a concave sound source representing a focused ultrasonic transducer based on the initial position and angle of the ultrasonic transducer, performing forward transcranial ultrasonic sound field simulation calculation, and thereby obtaining the position of the simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer; (c) calculating the distance between the ultrasonic transducer and the predetermined intracranial stimulation target at this time, and the distance between the ultrasonic transducer and the position of the simulated acoustic focus of the transcranial ultrasound sound field, and then calculating the position and angle of the ultrasonic transducer in the intermediate rounds using a gradient descent method; (d) placing a concave sound source representing a focused ultrasonic transducer based on the position and angle of the ultrasonic transducer in the intermediate round calculated in step (c), and performing a forward transcranial ultrasonic sound field simulation calculation to obtain a simulated acoustic focus of the transcranial ultrasonic sound field generated by the ultrasonic transducer in this round; (e) Repeating iterative steps (c) and (d), and stopping the iteration when the iterative stopping condition is reached, thereby obtaining the optimal position and angle of the ultrasonic transducer for navigation; wherein the position and angle of the ultrasonic transducer used in each round of iterative calculation are obtained based on the results of the previous round of iterative calculation based on the gradient descent method.

2. The method according to claim 1, wherein Step (c) also includes: before using the gradient descent method to calculate the position and angle of the ultrasonic transducer in the intermediate round, including the step of smoothing the transcranial ultrasonic sound field obtained at this time by ultrasonic sound field simulation calculation, so that there is no local minimum point in the half-maximum full width area of the smoothed transcranial ultrasonic sound field, and there is no local maximum point outside the maximum sound pressure value point.

3. The method according to claim 2, wherein The step of smoothing the transcranial ultrasonic sound field obtained by ultrasonic sound field simulation calculation occurs after calculating in step (c) the distance between the ultrasonic transducer and the predetermined stimulation target point in the skull and the distance between the ultrasonic transducer and the position of the simulated acoustic focus of the transcranial ultrasonic sound field.

4. The method according to claim 2, wherein The transcranial ultrasound sound field obtained by simulation calculation is smoothed by using a smoothing filter algorithm. Therefore, when the position and angle of the ultrasound transducer are calculated in the next intermediate round using the gradient descent method, the gradient of the smoothed transcranial ultrasound sound field at the predetermined stimulation target point P0 needs to be determined.

5. The method according to claim 4, wherein In step (b), a large number of point sound sources are set at various positions of the concave sound source. By performing transcranial sound field simulation calculations, the half-maximum full width area of the transcranial ultrasound sound field can be obtained, and the geometric center point or peak point of the area is used as the simulated acoustic focus of the transcranial ultrasound sound field generated by the ultrasonic transducer.

6. The method according to claim 5, wherein In step (c), in the first round of iterative calculation, the distance d between the ultrasonic transducer and the predetermined intracranial stimulation target is calculated by the following formula: 1,0 , and the distance d between the ultrasonic transducer and the position of the ultrasonic transducer simulated acoustic focus 1,b : the 1,0 =|P0-P 1,a |; d 1,b =|P 1,b -P 1,a |; Among them, P0 is the location of the predetermined stimulation target in the brain, P 1,a is the initial position of the ultrasonic transducer, P 1,b The position of the transcranial simulated acoustic focus of the ultrasonic transducer obtained by the ultrasonic sound field simulation calculation in step (b).

7. The method according to claim 6, wherein In step (c), the position and angle of the ultrasonic transducer in the intermediate rounds are calculated by using the gradient descent method, which includes: in the first round of iterative calculation, To calculate the angle and position of the ultrasonic transducer for the first intermediate round, Angle of the ultrasonic transducer in the first intermediate round Determine according to the following calculation formula: Where l is the set iteration step size; The position P of the ultrasonic transducer in the first intermediate round 2,a Determine according to the following calculation formula:

8. The method according to claim 7, wherein The iteration step length l is between.

9. The method according to claim 7, wherein: The iteration stopping condition is: when the number of iteration rounds is greater than a preset iteration round number threshold N, the iteration is stopped.

10. The method according to claim 7, wherein The iteration stopping condition is: when the number of iteration rounds is n, P n,b When the distance error between P0 and P0 is less than a preset navigation space error threshold e, or when the decrease in the navigation space error value obtained in two adjacent iterations is less than a preset threshold, the iteration is stopped.

11. The method according to claim 7, wherein The specific iterative calculation formulas for the angle and position of the ultrasonic transducer in steps (c) and (d) are as follows: Where m=1,2,… is the number of iterations, P m,a is the position of the ultrasonic transducer in the mth round of transcranial ultrasound sound field simulation calculation, P m,b is the position of the simulated acoustic focus of the transcranial ultrasound sound field generated by the ultrasound transducer obtained in the mth round of transcranial ultrasound sound field simulation calculation, is the simulated sound field gradient of the transcranial ultrasound sound field at the predetermined stimulation target point P0 obtained by the mth round of sound field simulation calculation, is the angle of the ultrasonic transducer in the mth intermediate round, P m+1,a is the position of the ultrasonic transducer in the mth intermediate round.

12. The method according to claim 11, wherein It is the simulated sound field gradient of the smoothed transcranial ultrasound sound field at the predetermined stimulation target point P0 after smoothing the transcranial ultrasound sound field obtained by the mth round of sound field simulation calculation using the Gaussian smoothing filter algorithm.

13. The method according to claim 1, wherein The method for simulating and calculating the transcranial ultrasound sound field adopts the k-space pseudo-spectral method.

14. The method according to claim 1, wherein The ultrasonic transducer is a single array ultrasonic transducer or an array composed of multiple ultrasonic transducers.

15. The method according to claim 1, wherein Before step (a), the method further includes step (a0): preprocessing the image data of the subject's head to obtain a structural model of the subject's head and sound field simulation medium data, wherein the sound field simulation medium data is used to establish a sound field calculation model of ultrasound passing through the skull.

16. The method according to claim 15, wherein The method also includes a registration and alignment step, which converts the position and angle of the optimal ultrasonic transducer of the head in the real coordinate system into the corresponding position and angle of the head structure model in the image coordinate system of the graphical interface based on the subject's head structure model, thereby guiding the ultrasonic transducer in the real coordinate system to the specified position in the image coordinate system of the graphical interface.

17. The method according to claim 16, wherein The registration step also includes selecting corresponding points of human facial feature points in the image coordinate system on the subject's head structure model to form a pairing point set, and using a rigid body to obtain the positions of the human facial feature points selected in the image coordinate system in the real coordinate system.

18. The method according to claim 17, wherein The number of facial feature points of the human body is 3 or more.

19. The method according to claim 18, wherein The facial feature points are selected from the following group: the outer end of the eye socket, the distal end of the ear, the base of the earlobe, the tip of the nose, the root of the nose, or the corner of the lip.

20. The method according to any one of claims 16 to 19, wherein The registration and alignment step performs pairing calculation on feature points through the singular value decomposition method to achieve registration and alignment.

21. The method according to any one of claims 16 to 19, wherein: The registration and alignment step occurs before, after, or simultaneously with the sound field simulation calculation step; to avoid the subject from waiting, the registration and alignment step can be performed after the sound field simulation calculation step.

22. A real-time navigation system for an ultrasound transducer for transcranial ultrasound stimulation, characterized in that: include: An image preprocessing module, configured to preprocess image data of the subject's skull to obtain a structural model of the subject's skull and sound field simulation medium data; an acoustic field simulation calculation module configured to establish an ultrasonic acoustic field simulation calculation model based on the acoustic field simulation medium data, adjust the position and angle of the transducer by a gradient descent method, and perform acoustic field calculations to obtain an optimal ultrasonic transducer orientation and position; The registration and alignment module is configured to convert the position and angle of the optimal ultrasound transducer of the skull in the real coordinate system and the corresponding position and angle in the skull structure model in the image coordinate system based on the subject's skull structure model.

23. The system of claim 22, wherein: The system also includes a space tracking and positioning device, which is configured to use an infrared optical tracking and positioning device to obtain coordinate data of the positioning rigid body in a real space coordinate system.

24. The system of claim 23, wherein: The spatial tracking and positioning device includes a first rigid body, a second rigid body and a third rigid body. The first rigid body points to a feature point on the surface of the skull in the real space coordinate system and is used to obtain the coordinate data of the feature point in the real coordinate system during registration and alignment. The second rigid body is bound to the ultrasonic transducer and is calibrated with the ultrasonic transducer to obtain the coordinate data of the ultrasonic transducer in the real coordinate system. The third rigid body is bound to the subject's head and is used to obtain the coordinate data of the head in the real coordinate system to track the spatial position of the head.

25. The system of claim 22, wherein: The system further includes a device communication module, which is configured to obtain position and angle data of the first rigid body, the second rigid body, and the third rigid body in a real coordinate system in real time, and transmit the obtained data to the registration and alignment module.

26. The system of claim 22, wherein: The system further includes a real-time navigation module configured to display a specific position and angle of the ultrasound transducer in the image coordinate system in real time and guide the ultrasound transducer to an optimal position and angle.

27. The system of claim 22, wherein: The image preprocessing module is also configured to visually display a three-dimensional model of the skull, and to display the relative position and angular relationship between the ultrasonic transducer and the predetermined stimulation target in the skull and the expected ultrasonic transducer position, and to superimpose the transcranial ultrasonic sound field distribution generated by the ultrasonic transducer at the expected ultrasonic transducer position and angle on the skull structure model in real time.

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