Method and device for guiding operation and control of sound tweezers through interactive ultrasonic real-time imaging

Abstract

The technical problem to be solved by the invention is how to guide the sound tweezers to control micro-nano particles through imaging feedback. Therefore, the invention discloses a visual interactive or automatic targeted sound tweezers micro-nano particle control method and a sound tweezers device, sound tweezers control is guided through ultrasonic imaging information, and target object interactive control and visualization of feedback type sound tweezers in biological tissues are realized. Specifically, an object is positioned through imaging or the position of a target area is automatically determined through feature recognition of an imaging result, and then acoustic tweezers parameters are fed back and modified, so that the acoustic tweezers are focused to the target area, and the effects of accurate targeting and artificial deviation getting rid of are achieved.

Description

Technical Field

[0001] The present invention relates to the field of acoustic manipulation technology, and in particular to a method for interactive ultrasonic real-time imaging guided acoustic manipulation and an acoustic tweezers device. Background Art

[0002] Compared with optical tweezers, acoustic tweezers have the advantages of less thermal damage and larger scale of captured objects. Whether in the field of surgery or in the field of targeted drug delivery in vivo, acoustic tweezers have great research significance and application value. In order to be able to manipulate tiny particles more accurately, acoustic tweezers targeted drug delivery guided by imaging visualization is a considerable challenge.

[0003] However, the imaging guidance methods required for acoustic tweezers are currently very scarce. In fact, ultrasound can image deep blood vessels, and the equipment is portable and has no radiation, making it very suitable as an imaging guidance method for acoustic tweezers. The feedback correction of acoustic tweezers by ultrasound imaging can be achieved through a single probe, dual probes, or multiple probes. In particular, a single matrix probe can obtain isotropic volume imaging results in a single transmission and reception, without the need for mechanical scanning like a linear probe, and the imaging coordinate system and the acoustic tweezers coordinate system remain consistent, without the need for alignment. However, when using dual and multiple probes, the imaging coordinate system is not the same as the acoustic tweezers coordinate system, and the dual and multiple systems need to be aligned. Regardless of the strategy chosen, the imaging result is a common problem that needs to be solved urgently. Summary of the invention

[0004] The technical problem to be solved by the present invention is how to guide the manipulation of micro-nano particles by acoustic tweezers through imaging feedback. To this end, the present invention discloses a method and an acoustic tweezers device for visually interactive or automatically targeted acoustic tweezers to manipulate micro-nano particles, which guides the manipulation of acoustic tweezers through ultrasonic imaging information, thereby realizing interactive manipulation and visualization of target objects by feedback-type acoustic tweezers in biological tissues. Specifically, the object is positioned by imaging or the target area is automatically determined by identifying the features of the imaging results, and then the acoustic tweezers parameters are modified by feedback to focus on the target area, thereby achieving precise targeting and getting rid of human bias. The acoustic field emission pulse sequence is composed of an imaging pulse sequence unit and an acoustic tweezers pulse sequence unit; it includes the following steps.

[0005] 1) Injecting micron or nanometer-scale manipulated particles into blood vessels;

[0006] 2) S1 is emitted through the excitation unit A in the time period t1, and the echo signal is transmitted to the ultrasound imaging reconstruction unit B for reconstruction, and the imaging result is displayed through the visualization interaction unit C; wherein the parameters of S1 are determined by the classical ultrasound imaging method;

[0007] 3) In the imaging area, the acoustic tweezers action area G1 is obtained by manual interaction; or the acoustic tweezers action area G1 is automatically obtained by pattern recognition or machine learning methods according to target features given by the user;

[0008] 4) According to the position information of G1, the parameters of the excitation pulse design unit D are updated, and the parameters are passed to the pulse sequence calculation unit E. Unit E obtains the parameters of the acoustic tweezers pulse sequence unit S2 through the angular spectrum propagation algorithm and the delay algorithm;

[0009] 5) Controlling the ultrasonic transducer to emit the acoustic tweezers pulse sequence unit S2 for G1 through the excitation unit A within the time period t2, that is, forming a focused acoustic vortex potential well in the action area G1, and completing the capture of the manipulated particles in the action area G1;

[0010] 6) Repeat steps 2), 3), 4), and 5) continuously, and manually specify or automatically identify a new action area G2 to achieve manual interactive or automatic acoustic tweezers to capture micro-nano particles.

[0011] The acoustic tweezers pulse sequence unit S2 is characterized in that, according to the focal area G2, the excitation delay parameters of each element of the transducer are obtained by using the angular spectrum propagation algorithm, and other excitation signal parameters include: signal voltage, pulse repetition frequency, number of cycles, and echo waiting time set by the user. The acoustic tweezers pulse sequence unit S2 is emitted to realize the acoustic vortex potential well in the specified acoustic tweezers focal area G2; the specific steps are:

[0012] 1) Obtain the delay matrix M1 of each array element focused on the G2 area through the classic delay algorithm;

[0013] 2) The delay matrix M2 of each array element of the transducer that constructs the acoustic vortex potential well is obtained through the angular spectrum propagation algorithm; 3) The final delay parameter matrix M of each array element is obtained by adding its own M1 and M2.

[0014] The present invention also provides a device for interactive ultrasonic real-time imaging to guide acoustic tweezers manipulation, characterized in that the device is composed of the following units:

[0015] 1) Pulse sequence calculation unit E and ultrasound imaging reconstruction unit B: responsible for calculating and setting the parameters of S1 and S2 according to the methods described in claims 1 and 2, and then generating and saving S1 and S2; receiving the echo signal of the transducer array, calculating and reconstructing the ultrasound image;

[0016] 2) Excitation unit A: responsible for loading S1 and S2, and providing ultrasonic excitation signals to each element of the transducer in an alternating manner of S1 and S2 according to claim 1;

[0017] 3) Single probe transducer array: Based on the excitation signal provided by the excitation unit, it is responsible for transmitting and receiving ultrasonic excitation signals, completing the imaging of the specified area and the capture of the manipulated particles; the transducer array includes a one-dimensional array, a two-dimensional matrix array, and a ring array;

[0018] 4) Visualization interaction unit C: responsible for displaying the real-time results of ultrasonic imaging, and prompting the user to select the target area where the acoustic vortex potential well needs to be generated by the mouse. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 A schematic diagram of the method and device provided by the present invention for interactive object manipulation using interactive ultrasonic real-time imaging to guide acoustic tweezers manipulation (taking a single probe configuration as an example to better understand the present invention, but the present invention is not limited to this).

[0020] Figure 2 The present invention provides an emission timing diagram of the imaging pulse sequence unit S1 and the acoustic tweezers pulse sequence unit S2. Implementation

[0021] The present invention is further described below by means of specific examples to provide a better understanding of the present invention, but the present invention is not limited thereto.

[0022] like Figure 1 As shown, in a specific embodiment, micron-sized microbubbles are the objects of acoustic tweezer manipulation; microbubbles have a more obvious acoustic impedance difference with biological blood cells and tissues, which can provide a source of contrast for imaging; it is worth noting that if the manipulated particles are drug-loaded microbubbles and drug-loaded nanodroplets of micron to nanometer scale, accurate target drug release can be achieved through acoustic tweezer manipulation. The manipulated particles include but are not limited to contrast microbubbles, drug-loaded microbubbles, nanodroplets, drug-loaded nanodroplets, and magnetic particles.

[0023] In one embodiment, the user interaction interface includes an excitation pulse design unit D and a visualization interaction unit C; the visualization interaction unit C is used to visualize B-mode ultrasound imaging and provide the user with specific location information of the target area G1 by clicking the mouse, that is, to determine the target area of ​​the acoustic vortex potential trap. Imaging modes include but are not limited to ultrasound B-mode imaging, contrast imaging, and ultrasound super-resolution imaging. In fact, the target area G1 can also be automatically determined by feature recognition provided by the user.

[0024] After each modification and determination of the region of interest G1, the acoustic tweezers acoustic field focal position is updated to G1, and it is passed to the excitation pulse design unit D. The excitation pulse design unit D passes the updated pulse parameters and focal position to the pulse sequence calculation unit E. The calculation unit E updates the acoustic field delay parameters and user-defined parameters, and passes the updated parameters to the excitation unit A. The excitation unit A emits the imaging pulse sequence unit S1 in the time period t1, excites the transducer array, emits the imaging acoustic field, and transmits the echo signal to the ultrasonic imaging reconstruction unit B to image the biological tissue. After that, the ultrasonic transducer is serially controlled to emit the acoustic tweezers pulse sequence unit S2 for the G1 region in the time period t2, which is responsible for manipulating the manipulated particles in G1. At this time, the user can continue to click the region of interest G2 with the mouse. Repeat the above steps to control the ultrasonic transducer to emit the acoustic tweezers pulse sequence unit S2 for the G2 region, which is responsible for manipulating the manipulated particles in G2, and realize interactive ultrasonic real-time imaging to guide acoustic tweezers manipulation.

[0025] like Figure 2 As shown, the present invention provides an imaging pulse sequence unit S1 and an acoustic tweezers pulse sequence unit S2 emission timing diagram. In a specific embodiment, in the t1 time period, the imaging pulse sequence unit S1 is emitted, and the imaging pulse sequence unit S1 includes the following parameters: signal voltage (5v), number of pulses (60), pulse repetition frequency (10kHz), number of pulse cycles (2), echo waiting time (10 microseconds), and delay parameters of each array element. Then, the acoustic tweezers pulse sequence unit S2 is emitted, and the acoustic tweezers pulse sequence unit S2 includes the following parameters: signal voltage (5v), number of pulses (5000), pulse repetition frequency (10kHz), number of pulse cycles (2), and delay parameters of each array element. The S1 and S2 units are emitted cyclically.

Claims

1. A method for capturing micro-nano particles using acoustic tweezers, characterized in that: Based on the real-time ultrasonic imaging results, the micro-nano particles are captured by visual interactive or automatic targeted acoustic tweezers; the acoustic field emission pulse sequence is composed of multiple imaging pulse sequence units S1 and acoustic tweezers pulse sequence units S2 in an alternating manner; the following steps are included: 1) Injecting micron or nanometer-scale manipulated particles into blood vessels; 2) S1 is emitted in time period t1, and the region of interest G1 is displayed through the visualization module A; wherein the parameters of S1 are determined by the classical ultrasound imaging method; 3) In the region of interest G1, the acoustic tweezers action region G2 is obtained by manual interaction; or the acoustic tweezers action region G2 is automatically obtained by pattern recognition or machine learning methods based on the target features given by the user; 4) According to G2, the parameters of the acoustic tweezers pulse sequence unit S2 are obtained through the angular spectrum propagation algorithm and the delay algorithm; 5) Control the ultrasonic transducer to emit the acoustic tweezers pulse sequence unit S2 for G2 within the time period t2, that is, to form a focused acoustic vortex potential well in the action area G2, and complete the capture of the manipulated particles in the action area G2; 6) Continuously repeat steps 2), 3), 4), and 5) to achieve artificial interactive or automatic acoustic tweezers to capture micro-nanoparticles.

2. The acoustic tweezers pulse sequence unit S2 according to claim 1, characterized in that: According to the focal area G2, the excitation delay parameters of each element of the transducer are obtained by using the angular spectrum propagation algorithm. Other excitation signal parameters include: signal voltage, pulse repetition frequency, number of cycles, and echo waiting time set by the user. The acoustic tweezers pulse sequence unit S2 is emitted to realize the acoustic vortex potential well in the specified acoustic tweezers focal area G2; the specific steps are: 1) Obtain the delay matrix M1 of each array element focused on the G2 region through the classic delay algorithm; 2) Obtain the delay matrix M2 of each array element of the transducer that constructs the acoustic vortex potential well through the angular spectrum propagation algorithm; 3) The final delay parameter matrix M of each array element is obtained by adding its own M1 and M2.

3. A device for interactive ultrasound real-time imaging to guide acoustic tweezers capture, characterized in that: The device consists of the following units: 1) Pulse sequence calculation and ultrasound imaging reconstruction unit: responsible for calculating and setting the parameters of S1 and S2 according to the methods described in claims 1 and 2, and then generating and saving S1 and S2; at the same time, receiving the echo signal of the transducer array, calculating and reconstructing the ultrasound image; 2) Excitation unit: responsible for loading S1 and S2, and providing ultrasonic excitation signals to each element of the transducer in an alternating manner of S1 and S2 according to claim 1; 3) Single probe transducer array: Based on the excitation signal provided by the excitation unit, it is responsible for transmitting and receiving ultrasonic excitation signals, completing the imaging of the specified area and the capture of the manipulated particles; the transducer array includes one-dimensional array, two-dimensional matrix array, and ring array; 4) Visualization interaction unit: responsible for the real-time display of ultrasonic imaging results, and prompting the user to select the target area where the acoustic vortex potential well needs to be generated by the mouse.

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