An ultrasound printing method, system, and storage medium for mimicking a blood vessel network

Abstract

An ultrasonic printing method, system and storage medium for an artificial blood vessel network. The ultrasonic printing method includes: obtaining preset printing information of the artificial blood vessel network, where the preset printing information includes a printing path and a printing cross-sectional area corresponding to each printing site on the printing path; determining a first cavitation intensity required for printing according to the phantom, and determining excitation parameters of at least two printing transducers; adjusting the position, shape and size of the confocal region of at least two printing transducers according to the preset printing information; determining that the cavitation intensity of the confocal region is greater than or equal to the first cavitation intensity, and starting to print the phantom; obtaining the actual printing cross-sectional area of the current printing site, and if it meets the preset printing information, controlling the confocal region to move to the next printing site to be printed. This application can directly print artificial blood vessel lumens on a cured soft tissue phantom, simplifying the printing process and greatly improving the printing efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of artificial blood vessel manufacturing, and particularly relates to an ultrasonic printing method, system and storage medium for an artificial blood vessel network. Background Art

[0002] The artificial blood vessel network is an important tool commonly used in biomedical experimental research and medical imaging equipment testing. For example, in biomedical drug release research, by attaching and planting vascular epithelial cells on the inner wall of the artificial blood vessel network, artificial blood vessels and organoids can be constructed to analyze the therapeutic effect of blood drugs on vascular epithelial cells. Another example is in the ultrasonic Doppler imaging of blood flow, where the artificial blood vessel network is commonly used to test the accuracy of blood flow imaging. The parameters of the artificial blood vessel network (such as lumen diameter, shape, number of bifurcated vessels, and flow rate, etc.) can determine the hemodynamic characteristics, so as to simulate pathological conditions (such as abnormal blood flow states caused by vascular stenosis), and then test the accuracy of different ultrasonic Doppler imaging algorithms.

[0003] Existing artificial blood vessel network printing technologies mostly adopt indirect methods, using sacrificial materials to indirectly form or solidify the soft tissue phantom outside the blood vessels. However, directly printing the lumen in soft tissues requires high penetration efficiency and control accuracy. Although existing lithography technologies have high printing accuracy, they have obvious light attenuation in opaque tissues and it is difficult to directly print blood vessel lumens. Summary of the Invention

[0004] The main technical problem to be solved by the present invention is the problem of low printing accuracy or difficult printing in existing artificial blood vessel printing methods.

[0005] According to a first aspect, in one embodiment, an ultrasonic printing method for an artificial blood vessel network is provided, including:

[0006] Obtaining preset printing information of the artificial blood vessel network, where the preset printing information includes a printing path and the printing cross-sectional area corresponding to each printing site on the printing path;

[0007] Determining a first cavitation intensity and a second cavitation intensity required for printing according to the phantom, and determining the excitation parameters of at least two printing transducers;

[0008] Adjusting the position, shape and size of the confocal region of at least two printing transducers according to the preset printing information;

[0009] Determining that the cavitation intensity in the confocal region is greater than or equal to the first cavitation intensity and the cavitation intensity in the region other than the confocal region is less than the second cavitation intensity, and starting to print the phantom;

[0010] Obtain the actual printing cross-sectional area of the current printing site. If the preset printing information is satisfied, control the confocal region to move to the next printing site to be printed, and adjust the size of the confocal region according to the printing cross-sectional area required by the next printing site to be printed; if the preset printing information is not satisfied, continue printing at the current printing site, and obtain the actual printing cross-sectional area of the current printing site again after a preset interval time.

[0011] According to a second aspect, in one embodiment, an ultrasonic printing system for simulating a blood vessel network is provided, including:

[0012] At least two printing transducers, the printing transducers are used to emit a first ultrasonic signal, and the first ultrasonic signals of the at least two printing transducers form a confocal region;

[0013] A first motion mechanism for driving the printing transducers to perform relative motion to adjust the shape and size of the confocal region and the first position of the confocal region relative to the first motion mechanism;

[0014] A second motion mechanism for driving the first motion mechanism to move, and the printing transducers move with the first motion mechanism to adjust the second position of the confocal region relative to the phantom;

[0015] A control module for:

[0016] Obtain the preset printing information of the simulated blood vessel network, where the preset printing information includes a printing path and the printing cross-sectional area corresponding to each printing site on the printing path;

[0017] Determine the first cavitation intensity and the second cavitation intensity required for printing according to the phantom, and determine the excitation parameters of the at least two printing transducers;

[0018] Adjust the position, shape and size of the confocal region of the at least two printing transducers according to the preset printing information;

[0019] Determine that the cavitation intensity of the confocal region is greater than or equal to the first cavitation intensity and the cavitation intensity of the region other than the confocal region is less than the second cavitation intensity, and start printing the phantom;

[0020] Obtain the actual printing cross-sectional area of the current printing site. If the preset printing information is satisfied, control the confocal region to move to the next printing site to be printed, and adjust the size of the confocal region according to the printing cross-sectional area required by the next printing site to be printed; if the preset printing information is not satisfied, continue printing at the current printing site, and obtain the actual printing cross-sectional area of the current printing site again after a preset interval time.

[0021] According to a third aspect, in one embodiment, a computer-readable storage medium is provided, on which a program is stored, and the program can be executed by a processor to implement the method described in the first aspect.

[0022] According to the ultrasonic printing method, system and storage medium of the vascular network simulation in the above embodiment, by using at least two printing transducers to form a confocal region, and the size and shape of the confocal region can be adjusted, it is possible to realize complex vascular network simulation printing in a phantom using ultrasound. By directly printing the vascular lumen simulation in the already cured soft tissue phantom, the printing process is simplified and the printing efficiency is greatly improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic structural diagram (one) of an ultrasonic printing system provided by an embodiment of the present application;

[0024] Figure 2 It is a schematic structural diagram (two) of an ultrasonic printing system provided by an embodiment of the present application;

[0025] Figure 3 It is a schematic structural diagram (three) of an ultrasonic printing system provided by an embodiment of the present application;

[0026] Figure 4 It is a flowchart of an ultrasonic printing method provided by an embodiment of the present application;

[0027] Figure 5 It is a schematic diagram of the adjustment of the confocal region provided by an embodiment of the present application;

[0028] Figure 6 It is a schematic diagram of an ultrasonic image of a monitoring module provided by an embodiment of the present application;

[0029] Figure 7 It is a schematic diagram of the cavitation intensity collected by a monitoring module provided by an embodiment of the present application.

[0030] Reference numerals: 10 - printing transducer; 11 - confocal region; 20 - first motion mechanism; 21 - first fixture; 22 - second fixture; 23 - electric rotating shaft; 30 - second motion mechanism; 40 - monitoring module; 50 - control module; 51 - signal generator; 52 - signal amplifier; 53 - multi-channel pulse transceiver circuit; 100 - phantom. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0031] The present invention will be further described in detail below in conjunction with the specific embodiments and the accompanying drawings. Similar elements in different embodiments are denoted by related similar element numbers. In the following embodiments, many detailed descriptions are provided to enable a better understanding of the present application. However, those skilled in the art can easily recognize that some of the features can be omitted in different situations, or can be replaced by other elements, materials, or methods. In some cases, some operations related to the present application are not shown or described in the specification to avoid overwhelming the core part of the present application with excessive descriptions. For those skilled in the art, it is not necessary to describe these related operations in detail, and they can fully understand the related operations based on the descriptions in the specification and the general technical knowledge in the art.

[0032] In addition, the features, operations, or characteristics described in the specification can be combined in any suitable manner to form various embodiments. At the same time, the steps or actions in the method description can also be reordered or adjusted in an obvious manner by those skilled in the art. Therefore, the various sequences in the specification and the drawings are only for clearly describing a certain embodiment and do not mean that they are the necessary sequences, unless it is stated that a certain sequence must be followed.

[0033] The serial numbers assigned to the components herein, such as "first", "second", etc., are only used to distinguish the objects described and do not have any sequential or technical meaning. The terms "connection" and "coupling" used in the present application, unless otherwise specified, both include direct and indirect connection (coupling).

[0034] 3D printing is a feasible method for preparing a vascular network mimic, such as an indirect forming method based on the fused deposition modeling (FDM) printing technology. First, a sacrificial material for supporting the blood vessels is printed, and then the sacrificial material is placed in a container and infused with a tissue mimic solution. After the external tissue mimic solidifies, the internal 3D-printed sacrificial material is removed to obtain a vascular network mimic. The printing resolution of the FDM printing method is affected by the material properties and nozzle size, and it is prone to situations such as clogging of the sacrificial material and rupture of the mimic. Moreover, the indirect forming method has cumbersome steps and is not suitable for the fabrication of vascular network mimics with complex branches and small diameters.

[0035] Another existing technology is stereolithography, also known as Stereolithography for Tissue Engineering (SLATE) technology, which uses lasers or ultraviolet projections to precisely cure polymers, converting them from fluids to solids. The light prints each two-dimensional slice of blood vessels at a high resolution with pixel sizes ranging from 10 to 50 micrometers. When one layer is photo-cured, the light spot is moved to continue the photo-curing of the liquid to complete the printing of the next two-dimensional slice of blood vessels. Finally, the three-dimensional blood vessel-like network is printed layer by layer. The SLATE technology utilizes the stereolithography technology of phantom materials, which has limitations on phantom materials and requires optical equipment with high printing resolution. Moreover, this line-by-line printing method is relatively time-consuming, especially when printing large-volume structures. In addition, there is significant light attenuation of this light in opaque phantoms and human tissues, and deep printing cannot be completed. Therefore, it is difficult to achieve remote printing with stereolithography.

[0036] Therefore, in the existing FDM and SLATE methods, it is still difficult to construct blood vessel-like networks. These blood vessel phantoms not only need to maintain sufficient mechanical strength and viscoelasticity similar to human tissues for a certain period of time to withstand external pressure and high internal blood flow rates, but also require high biocompatibility and safety. More importantly, in order to be similar to the human blood vessel system, the blood vessel-like network should be distributed and connected in three-dimensional space, and there are lumen configurations with different diameters, directions, and bifurcations in the network. Currently, there is still a need for technological breakthroughs in the fabrication of three-dimensional complex blood vessel-like networks.

[0037] This application provides a printing system and method for an in vitro blood vessel-like network, which performs three-dimensional printing through ultrasonic waves. A soft tissue phantom 100 is placed in a container filled with a coupling agent (such as water). A high-intensity ultrasonic transducer is placed outside the phantom 100 as the printing transducer 10. At least two printing transducers 10 focus the acoustic energy into the acoustic focal region in the container through a confocal method. The acoustic cavitation effect at the solid-liquid interface in the acoustic focal region is used to slightly damage the soft tissue phantom 100 to form cavities. The second motion mechanism 30 (such as a programmable numerical control robotic arm) is used to control the movement of the focus of the printing transducer 10 to achieve remote in vitro printing of a blood vessel-like network with a complex structure without physical contact with the printing site. Compared with optical printing, the above printing method has the characteristics of fixed focus and good penetrability, can penetrate the soft tissue phantom 100 and print within a range of more than ten centimeters, and no toxic by-compounds are produced. Compared with the above FDM and SLATE methods, the ultrasonic printing method proposed in this application can directly print hollow tubular structures, and the tubular structures can achieve millimeter-level control accuracy without sacrificing materials. At the same time, the propagation of ultrasonic energy has little attenuation in opaque phantoms 100 and human tissues, and deep and opaque printing can be achieved.

[0038] In this application, the phantom 100 can be made of materials such as agar, gelatin, or polyvinyl alcohol because their acoustic and mechanical properties are close to those of real soft tissues.

[0039] The present application also provides a material and a preparation method for a soft tissue phantom 100. The phantom material can be selected from sodium alginate or acrylamide. By crosslinking a 40% g / ml acrylamide solution, a 10% g / ml ammonium persulfate solution, a crosslinking agent N-N'-methylenebisacrylamide, a calcium chloride solution, and a 3% g / ml sodium alginate solution, a soft tissue phantom 100 with high mechanical strength can be prepared. Of course, the phantom material can also be other natural or synthetic materials with high biocompatibility and acoustic and mechanical properties similar to those of human soft tissue. To avoid the rupture of the phantom 100 during the printing process, a phantom material with a certain mechanical strength is preferably selected, and the acoustic excitation parameters are controlled. By adjusting the composition, ratio of the above printing materials, and the external environmental conditions during the curing process, the material properties of the soft tissue phantom 100 can be adjusted. For example, by increasing the ratio of PDMS and photoinitiator during the curing process of polydimethylsiloxane (PDMS), the cured soft tissue phantom 100 can be made more uniform and transparent.

[0040] The ultrasonic printing system and method for simulating a vascular network provided by the present application will be specifically described below.

[0041] As Figure 1 shown, an ultrasonic printing system for simulating a vascular network provided by an embodiment of the present application may include: at least two printing transducers 10, a first motion mechanism 20, a second motion mechanism 30, and a control module 50. In some embodiments, the ultrasonic printing system may further include a monitoring module 40.

[0042] As Figure 2 shown, there are at least two printing transducers 10, which may be three, four, etc. The printing transducers 10 are used to emit a first ultrasonic signal. The emission centerlines of at least two printing transducers 10 intersect, and the first ultrasonic signals of at least two printing transducers 10 form a confocal region 11. The confocal region 11 may also be referred to as a printing lumen region, an acoustic printing region, or an acoustic focus region. Without special instructions, the present application takes two printing transducers 10 as an example for illustration.

[0043] Although existing high-intensity ultrasonic transducers can focus acoustic energy into a focal region in space, the focal region of a single ultrasonic transducer (with a major axis of about 8 - 20 mm and a minor axis of about 1.5 - 5 mm) is still relatively large, and the shape of the focal region is "elliptical" or "long spindle-shaped", and at the same time, the size and shape of the focal region are fixed and unchangeable. An embodiment of the present application proposes a method of using confocal mode of two high-intensity ultrasonic transducers. By changing the acoustic beam angle and intersection position of the acoustic fields of the two transducers through the first motion mechanism 20, the shape and size of the acoustic printing region (confocal region 11) can be changed, so as to realize the printing of a simulated vascular network with different diameters.

[0044] As shown Figure 2 in FIG. 1, the first motion mechanism 20 is used to drive relative motion between a plurality of printing transducers 10 to adjust the shape and size of the confocal region 11, and the first position of the confocal region 11 relative to the first motion mechanism 20. Among them, the first motion mechanism 20 may include a first fixture 21, a plurality of second fixtures 22, and a plurality of electric rotating shafts 23, and the printing transducers 10 are mounted on the electric rotating shafts 23. Through the electric rotating shafts 23, the printing transducers 10 can be driven to rotate relative to the second fixtures 22; the second fixtures 22 can swing or rotate relative to the first fixture 21 so that the included angle of the brackets of the plurality of second fixtures 22 changes, and the printing transducers 10 can move following the rotation of the second fixtures 22.

[0045] As shown Figure 3 in FIG. 2, the ultrasonic parameters / excitation parameters (frequency, pulse width, pulse repetition frequency, etc.) of two high-intensity ultrasonic transducers in the acoustic printing area can be synchronized and controlled by a signal generator 51. By changing the focusing shape and size in a confocal manner, and by controlling the acoustic energy intensity, blood vessel mimics with a cross-sectional area of 0.75 mm 2 -12 mm 2 can be printed. By moving the confocal region 11 vertically and horizontally to expand the tube diameter, blood vessel mimics with a cross-sectional area greater than 50 mm 2 can be printed. A complex blood vessel network can be planned for the printing path by the second motion mechanism 30.

[0046] As shown Figure 1 in FIG. 3 Figure 2 and FIG. 4, the monitoring module 40 is mounted on the first motion mechanism 20. The monitoring module 40 is used to emit a second ultrasonic signal to the phantom 100 and receive the second echo signal of the second ultrasonic signal; it is also used to receive the first echo signal of the first ultrasonic signal.

[0047] To ensure the reliability and accuracy of the acoustic printing process, the present application adds a monitoring module 40 to the acoustic printing process. The monitoring module 40 may include a monitoring ultrasonic imaging probe, which can perform cavitation intensity imaging during the printing process of the printing transducers 10 and perform quantitative evaluation imaging on the size of the lumen after printing.

[0048] In some embodiments, the above-mentioned monitoring ultrasonic imaging probe can be replaced by a passive hydrophone. The passive hydrophone can be connected to the input end of an oscilloscope by a wired connection to monitor the backscattered echo of the printing transducer 10 and obtain cavitation intensity information. In other embodiments, the ultrasonic printing system may further include a high-speed optical camera, and the high-speed optical camera can be mounted on the wall of the above-mentioned container to further observe the printing process.

[0049] As shown Figure 1 in the figure, the second motion mechanism 30 is used to drive the first motion mechanism 20 to move, and the printing transducer 10 and the monitoring module 40 move along with the first motion mechanism 20 to adjust the second position of the confocal region 11 relative to the phantom 100. For example, the second motion mechanism can be a programmable numerically controlled robotic arm.

[0050] In the embodiment of the present application, the second motion mechanism 30 may include a programmable numerically controlled robotic arm. The printing transducer 10 is fixed on the first motion mechanism 20. The whole of the printing transducer 10, the monitoring module 40, and the first motion mechanism 20 can be referred to as the printing front end. By moving the printing front end, the confocal region 11 is moved to perform remote direct printing in space. Since the confocal region 11 heats up quickly and has little impact on the soft tissue phantom 100 outside the confocal region 11, the line-by-line printing rate and printing resolution are also limited by the moving rate and moving accuracy of the programmable numerically controlled robotic arm. The moving printing rate of the programmable numerically controlled robotic arm can reach 15000mm 3 -35000mm 3 / h.

[0051] The control module 50 is used to control the operation of the printing transducer 10, the first motion mechanism 20, the second motion mechanism 30, and the monitoring module 40. For example, a multi-array ultrasonic imaging transducer can be used as the ultrasonic imaging probe of the monitoring module 40, and its ultrasonic emission center line intersects with the emission center line of the printing transducer 10. The ultrasonic imaging probe can switch between two working modes: actively emitting pulse scanning imaging (i.e., emitting a second ultrasonic signal and obtaining its second echo signal) and passively receiving the echo of the printing transducer 10 (i.e., the first echo signal of the first ultrasonic signal). The control module 50 uses corresponding algorithms to obtain the spatial position information of the printing site (corresponding to the center position of the confocal region 11), the printing tube diameter area (or called the printing cross-sectional area), and the cavitation intensity information. According to the spatial position information of the printing site, it controls the programmable numerically controlled robotic arm to compensate the spatial position of the first motion mechanism 20 in real time. According to the cavitation intensity information, it adjusts the emission parameters of the printing transducer 10 and the confocal settings. According to the gray level difference in the lumen before and after printing, it obtains the printing cross-sectional area, and further adjusts the confocal settings and the movement of the confocal region 11 to ensure the smooth progress of printing.

[0052] In some embodiments, the control module 50 may include a power supply, a signal generator 51, and a signal amplifier 52. The signal generator 51 and the signal amplifier 52 supply electrical energy to the printing transducer 10, which converts the electrical energy into acoustic energy, and finally outputs high-voltage ultrasonic waves that are focused at the acoustic focus. The size of the acoustic focus region (confocal region 11) directly affects the printing resolution of the vascular network simulation. Generally, the size of the acoustic focus region is related to the confocal settings, the curvature radius of the surface of each printing transducer 10, and the excitation parameters set by the signal generator 51 and the signal amplifier 52, especially related to the pulse repetition frequency and the pulse duration. It is necessary to optimize the acoustic excitation parameters to improve the printing resolution as much as possible. The center frequency of the printing transducer 10 can be between 1 MHz and 20 MHz, and preferably a frequency close to the center resonance frequency of the printing transducer 10 is used as the transmission center frequency of the printing transducer 10. Affected by the curvature radius of the transducer surface, the distance from the focus to the front end of the printing transducer 10 is between 30 mm and 60 mm, and the size of the acoustic focus area of a single printing transducer 10 is about 7 mm 2 -10 mm 2 or so. The size of the acoustic focus area after confocal can be selected within a large range. The excitation pulse repetition frequency of the printing transducer 10 is between 100 Hz and 10 kHz, and the pulse duration is between 20 μs and 20 ms. Optimizing the acoustic excitation parameters, such as a higher pulse repetition frequency and a shorter pulse duration, can improve the printing resolution to a certain extent. By changing the focused energy and the size of the acoustic focus region through confocal means, the printed pipe diameter area can be between 0.75 mm 2 -12 mm 2 . By controlling the up, down, left, and right movement and expansion of the confocal region 11 through the first motion mechanism 20, a pipe diameter with a cross-sectional area greater than 50 mm 2 can be printed.

[0053] In some embodiments, a multi-array ultrasonic imaging transducer can be installed at the print front end as a monitoring ultrasonic imaging probe (i.e., the monitoring module 40). The monitoring ultrasonic imaging probe is connected to the control module 50, can actively emit ultrasonic pulses, and reconstruct images using the echoes. Based on the images actively acquired by the monitoring ultrasonic imaging probe, the spatial position information of the printing site and the cross-sectional area of the tube after printing can be obtained. It is also possible to passively receive the echoes in the confocal acoustic focus region when the printing transducer 10 is working. Based on the echoes passively received by the monitoring ultrasonic imaging probe, broadband noise information related to the cavitation intensity at the confocal region 11 is obtained using spectral analysis methods and harmonic filtering methods, and the intensity value is calculated through algorithm analysis to quantify the cavitation intensity. The above-mentioned multiple printing transducers 10 for confocal imaging, the monitoring ultrasonic imaging probe, and the numerically controlled robotic arm together constitute the basis for the control of the ultrasonic printing system. During the printing process, the position of the printing transducer 10 and the output pulse parameters are continuously adjusted based on the data acquired by the monitoring ultrasonic imaging probe and algorithm analysis until the printing is completed.

[0054] The ultrasonic printing system will be further described in detail below.

[0055] As Figure 2 shown, the front stage of the system includes a print front end (i.e., the first motion mechanism 20) composed of a first fixture 21, a second fixture 22, and an electric rotating shaft 23. The printing transducer 10 is installed on the electric rotating shaft 23, and the monitoring module 40 is installed on the first fixture 21.

[0056] As Figure 2 shown, the two printing transducers 10 are fixed to the electric rotating shaft 23 in a hard connection manner and fixed to the print front end through the second fixture 22. As Figure 3 shown, the printing transducer 10 is connected to the output ends of the signal amplifier 52 and the signal generator 51 by a wired connection. The control module 50 is connected to the signal generator 51 by a wired connection to control the excitation parameters output by the signal generator 51 to the printing transducer 10. The excitation parameters include the emission center frequency, pulse duration, pulse repetition frequency, etc. The two electric rotating shafts 23 are connected to the control module 50 by a wired connection to control the front-stage electric rotating shaft 23 to adjust the beam angle and intersection position of the acoustic beams output by the two printing transducers 10.

[0057] As Figure 2As shown, the monitoring module 40 is fixed at the central position of the first motion mechanism 20 through the first fixture 21, aligned with the confocal region 11 of the printing transducer 10, and connected to the multi-channel pulse transceiver circuit 53 and the control module 50 by means of a wired connection. The control module 50 can control the monitoring ultrasonic imaging probe to emit imaging pulses through the multi-channel pulse transceiver circuit 53, and can also collect the echoes received by the monitoring ultrasonic imaging probe, and send the collected echo data back to the control module 50 to achieve spatial positioning, intensity analysis and morphological evaluation through echo analysis and image reconstruction, so as to realize real-time control of the system.

[0058] As Figure 2 shown, the printing front end (including a plurality of confocal printing transducers 10, a monitoring module 40 and a first motion mechanism 20) is fixed on the programmable numerically controlled robotic arm by means of a hard connection. The control module 50 controls the programmable numerically controlled robotic arm to move the printing front end through a wired connection, thereby realizing the movement of the confocal region 11 of the printing transducer 10. During printing, the above-mentioned printing front end and the illustrated soft tissue phantom 100 are both immersed in degassed water, and encapsulated microbubbles are added to the degassed water. The acoustic energy is focused on the solid-liquid interface between the soft tissue phantom 100 and the degassed water, triggering inertial cavitation of the encapsulated microbubbles at the solid-liquid interface, and using the acoustic cavitation effect to slightly damage the soft tissue phantom 100 to form cavities. The programmable numerically controlled robotic arm controls the movement of the printing front end, and prints a vascular lumen-like structure on the path where the acoustic focus moves. By setting the output parameters of the signal generator 51 through the control module 50, the confocal region 11 is set to change the cavitation intensity of the confocal region 11; by programming the printing path of the programmable numerically controlled robotic arm, a complex vascular network-like structure can be printed inside the soft tissue phantom 100.

[0059] In some embodiments, the ultrasonic printing system may further include a printing container. The printing container is used to hold a coupling agent (such as water, generally degassed water). When the ultrasonic printing system works, the phantom 100 is immersed in the coupling agent, and the printing transducer 10 and the monitoring module 40 emit ultrasonic signals to the phantom 100 through the coupling agent; that is, part or all of the printing transducer 10 and the monitoring module 40 are also immersed in water.

[0060] In some embodiments, acoustic-sensitive nanoparticles may be added to the coupling agent. The acoustic-sensitive nanoparticles are used to enhance the thermal effect, sonochemical reaction or acoustic cavitation effect of the first ultrasonic signal. The acoustic-sensitive nanoparticles may be microbubbles. Alternatively, other acoustic-sensitive nanoparticles may be added during the preparation process of the above-mentioned soft tissue phantom 100 to improve the effects of the thermal effect, sonochemical reaction or acoustic cavitation effect during the above-mentioned three-dimensional ultrasonic printing process.

[0061] For soft tissue phantoms 100 with high toughness, high acoustic energy is often required to achieve lumen printing, which to some extent limits the selection of excitation parameters and thus restricts the printing accuracy. To reduce the acoustic energy required for printing, inspired by the microbubble-enhanced acoustic cavitation effect, microbubbles are added to the water tank during three-dimensional ultrasonic printing to increase the printing efficiency, and microbubbles can also be added during the fabrication of the phantom 100 to increase the printing efficiency. Microbubbles are injected into the water and printing is performed at the solid-liquid interface to reduce the required acoustic energy and avoid damage outside the printing site. For example, the microbubbles used can have a single-layer phospholipid structure and be filled with C3F8.

[0062] For example, the printing container can be a container made of plexiglass. Before ex vivo printing, water is injected into the plexiglass container to couple acoustic energy, and then the soft tissue phantom 100 is placed into the container. The entire ex vivo three-dimensional ultrasonic printing process is carried out in the container. Microbubbles with internal gas nuclei and external envelopes at a specific concentration can be added to the water in the above container to enhance the acoustic cavitation effect and reduce the requirements for the excitation parameters of the printing transducer 10. The concentration range of the encapsulated microbubbles can be between 10 4 microbubbles / ml - 10 7 microbubbles / ml. Ex vivo three-dimensional ultrasonic printing adopts a remote printing method to control the printing front end fixed on a programmable numerically controlled robotic arm, so that the confocal region 11 of the confocal printing transducer 10 is aligned with the printing site at the solid-liquid interface of the soft tissue phantom 100 and water. During printing, the acoustic energy output by the confocal printing transducer 10 is focused on the solid-liquid interface, triggering inertial cavitation of the encapsulated microbubbles in the degassed water. The microbubbles collapse to generate energy, creating microdamage on the soft tissue phantom 100 at the solid-liquid interface and forming cavities. By controlling the printing front end with the programmable numerically controlled robotic arm and moving the focus of the above confocal printing transducer 10, lumens simulating a vascular network are printed along the path of the acoustic focus movement inside the soft tissue phantom 100. After printing, some of the separated phantom material enters the water through the simulated vascular network and does not block the already printed simulated vascular network.

[0063] Next, the specific process of the ultrasonic printing method for the ultrasonic printing system will be elaborated as follows, as Figure 4 shown. The method can include the following steps:

[0064] Step 1: Obtain the preset printing information of the blood vessel-like network. The preset printing information may include the printing path and the printing cross-sectional area corresponding to each printing site on the printing path. For example, before printing, the phantom 100 and the blood vessel-like network in the phantom 100 are designed through corresponding software, and the corresponding preset printing information is exported. Each printing site has determined spatial position information in the coordinate system of the second motion mechanism 30. Through the combined motion of the first motion mechanism 20 and the second motion mechanism 30, the confocal region 11 of the printing transducer 10 can be aligned with the printing site. For each printing site, the printing cross-sectional area can also be the same or different. The printing transducer 10 adjusts the size and shape of the confocal region 11 through the first motion mechanism 20 to match the printing cross-sectional area. Of course, the above preset printing information can be exported after software design or provided in a manual design manner. The present application does not limit the formation method of the preset printing information.

[0065] Step 2: Determine the first cavitation intensity required for printing according to the phantom 100, and determine the excitation parameters of at least two printing transducers 10.

[0066] In some embodiments, the phantom 100 generally has a first cavitation intensity. Microdamage will occur at the ultrasonic energy corresponding to the first cavitation intensity, and cavities will be formed. However, in some phantoms 100, at the ultrasonic energy corresponding to the second cavitation intensity (less than the first cavitation intensity), no microdamage occurs and cavities are not formed, but damage will be caused, affecting the performance of the phantom 100.

[0067] For example, a phantom 100 will have microdamage and form cavities at 1 unit of ultrasonic energy, and damage will occur at ultrasonic energy greater than 0.5 units. Therefore, the maximum ultrasonic energy emitted by a single printing transducer 10 cannot be greater than 0.5 units. At this time, three printing transducers 10 can be used, and each printing transducer 10 emits 0.33 units, so that the ultrasonic energy in the confocal region 11 of the three printing transducers 10 is 1 unit, and the ultrasonic energy in the region other than the confocal region 11 is less than 0.5 units. At this time, the phantom 100 will only have microdamage and form cavities in the confocal region 11, and no damage will occur in other regions, ensuring the performance of the phantom 100.

[0068] Therefore, in the embodiments of the present application, the first cavitation intensity, the second cavitation intensity, the number of printing transducers 10, and the excitation parameters corresponding to the maximum output ultrasonic of the printing transducers 10 are determined according to the phantom 100. To protect the performance of the phantom 100 on the premise of meeting the requirements of microdamage printing.

[0069] Step 3: Adjust the position, shape, and size of the confocal regions 11 of at least two printing transducers 10 according to the preset printing information.

[0070] In some embodiments, adjusting the position, shape, and size of the confocal region 11 of at least two printing transducers 10 may include:

[0071] Step 301: Adjust the beam angle θ and intersection position of at least two printing transducers 10 to adjust the shape and size of the confocal region 11.

[0072] As Figure 5 shown, the first motion mechanism 20 can adjust the angle between the printing transducer 10 and the second fixture 22 where it is located, and can also adjust the angle between the second fixture 22 and the first fixture 21, so that the confocal region 11 can be as Figure 5 in (a) Figure 5 change to (b) in the figure. At this time, the position of the confocal region 11 corresponding to the first position of the first motion mechanism 20 changes, and the shape and size also change.

[0073] In some embodiments, before starting to print the phantom 100, it may further include:

[0074] Step 302: Determine whether the actual starting printing site meets the requirements of the starting printing site in the preset printing information.

[0075] For example, by obtaining the spatial position information of the starting printing site in the preset printing information, and based on the structures of the first motion mechanism 20 and the second motion mechanism 30, the beam angle θ of the printing transducer 10, and the intersection position, etc., the position of the current confocal region 11 can be determined. If the deviation between the position of the current confocal region 11 and the starting printing site in the preset printing information is greater than the preset range, such as 0.5 mm, it is adjusted by the second motion mechanism 30.

[0076] In some embodiments, it may be after a pre-printing is performed, and the printing cross-sectional area of the pre-printing is smaller than the printing cross-sectional area of the starting printing site. By processing the second echo information of the second ultrasonic signal through the monitoring module 40, the position of the cavity formed by the pre-printing in the phantom 100 is determined, the position of the actual starting printing site is verified, and after determining whether the actual starting printing site meets the requirements of the starting printing site in the preset printing information, the formal printing is started. If the requirements are not met, the position of the actual starting printing site is adjusted according to the position of the cavity formed by the pre-printing in the phantom 100.

[0077] Step 4: Determine that the cavitation intensity of the confocal region 11 is greater than or equal to the first cavitation intensity, and start printing the phantom 100.

[0078] In some embodiments, determining that the cavitation intensity of the confocal region 11 is greater than or equal to the first cavitation intensity may include:

[0079] Step 401: Obtain the first echo signal generated by the confocal region 11, process the first echo signal to obtain the intensity of the corresponding broadband noise component, and quantify the cavitation intensity of the confocal region 11 with this.

[0080] Step 402: When the cavitation intensity is less than the first cavitation intensity, adjust the excitation parameters of the printing transducer 10 so that the cavitation intensity of the confocal region 11 is greater than or equal to the first cavitation intensity. The excitation parameters may include at least one of the emission center frequency, excitation voltage, pulse duration, and pulse repetition frequency.

[0081] Since the excitation parameters determined in step 2 are ideal design values, there must be a deviation in the actual cavitation intensity generated in the confocal region 11. Therefore, during the printing process, the monitoring module 40 obtains the first echo signal, analyzes the cavitation intensity, and adjusts the excitation parameters according to the actual cavitation intensity to meet the requirements of the printing cavitation intensity.

[0082] In some embodiments, processing the first echo signal may include:

[0083] Performing spectral analysis and / or beam synthesis on the first echo signal to obtain the intensity of the corresponding broadband noise component.

[0084] As Figure 6 shown, under the control of the control module 50, the multi-channel pulse transceiver circuit 53 and the monitoring ultrasonic imaging probe can switch between two working modes: actively emitting pulse scanning imaging and passively receiving the echo of the printing transducer 10. Before starting printing, the multi-channel pulse transceiver circuit 53 controls the monitoring ultrasonic imaging probe to actively emit imaging pulses for scanning imaging and receive the echo of the active imaging pulses. After receiving the echo, the control module 50 obtains the B-mode image through beam synthesis and image reconstruction (as shown in (a), (b), and (c) in Figure 6 ). Since the monitoring module 40 is aligned with the confocal region 11, the spatial position of the actual printing site can be determined from the B-mode image. Through the structural relationship between the first motion mechanism 20 and the second motion mechanism 30, the theoretical spatial position of the confocal region 11 can be obtained. The relative position difference between the theoretical spatial position of the confocal region 11 and the actual printing site can be calculated. And when necessary, the programmable numerical control robotic arm is controlled to appropriately adjust the position of the acoustic printing front end to compensate for the relative position difference to meet the printing requirements. Generally, before starting printing, the relative position difference between the actual spatial position of the starting printing point and the theoretical spatial position of the confocal region 11 is determined.

[0085] As Figure 7As shown, before formal printing, the control module 50 outputs an excitation to the printing transducer 10 through the signal generator 51 to emit a test ultrasonic pulse. At the same time, the multi-channel transceiver circuit passively receives the backscattered echo of the confocal region 11 through the monitoring module 40. After the control module 50 receives the echo, it performs spectral analysis on the backscattered echo through Fourier transform, and uses a band-pass filter and a band-stop filter to obtain the broadband noise component related to the cavitation intensity in the echo. The intensity of the broadband noise component is obtained by calculating the sum of squares of the filtered spectrum, so as to quantify the cavitation dose in the echo signal, determine whether the preset intensity is reached, and appropriately adjust the output parameters of the signal generator 51 to meet the printing requirements. When the cavitation dose is insufficient, the excitation voltage, pulse duration or pulse repetition frequency is increased by a preset increment. After determining that the printing position and the emitted pulses meet the printing requirements, the printing transducer 10 starts formal printing.

[0086] Step 5: Obtain the actual printing cross-sectional area of the current printing site. If it meets the preset printing information, control the confocal region 11 to move to the next printing site to be printed, and adjust the size of the confocal region 11 according to the printing cross-sectional area required by the next printing site to be printed; if it does not meet the preset printing information, continue printing at the current printing site, and obtain the actual printing cross-sectional area of the current printing site again after a preset interval.

[0087] In some embodiments, obtaining the actual printing cross-sectional area of the current printing site may include:

[0088] Step 501: Obtain the second echo signal of the second ultrasonic signal emitted by the monitoring module 40, obtain the cross-sectional image corresponding to the current printing site according to the second echo signal, and calculate the actual printing cross-sectional area of the current printing site according to the cross-sectional image.

[0089] During the actual printing process, it takes a certain amount of time for ultrasound to cause microdamage to the phantom 100 and form cavities, which is related to the material of the phantom 100, the concentration and composition of the sonosensitive nanoparticles in the coupling agent, and the excitation parameters of the printing transducer 10. Therefore, it is necessary to obtain the printing cross-sectional area at preset intervals, ensure that the actual printing cross-sectional area meets the requirements before printing the next printing site, and ensure the printing quality of the artificial blood vessel.

[0090] After the formal printing of the printing transducer 10 is completed, the monitoring module 40 is controlled by the multi-channel pulse transceiver circuit to perform active scanning imaging again to obtain a cross-sectional image of the printed blood vessel-like lumen. The control module 50 performs morphological analysis on the images of the printing sites before and after printing, calculates the lumen shape and area through an algorithm, and determines whether the lumen printing is completed. If the printing requirements are not met, the control module 50 appropriately adjusts the excitation time output by the signal generator 51 and the confocal region 11 settings until the printed lumen meets the requirements, and then the robotic arm controls the printing front end to move to the next printing site. The entire system is controlled by the control module 50 and operates continuously according to the preset parameters.

[0091] As Figure 5 shown, the angle and position between the two printing transducers 10 can be controlled by the second fixture 22 and the electric rotating shaft 23. The control module 50 adjusts the beam angle θ and the intersection position between the sound beams emitted by the printing transducers 10 through the electric rotating shaft 23, changes the shape and size of the confocal region 11, and prints blood vessel-like networks with different shapes and diameters.

[0092] As Figure 5 shown in (a) of [], the control module 50 controls the electric rotating shaft 23 to increase the sound field beam angle θ between the printing transducers 10. The emitted sound beams (the thicker regions near the transducers of the emitted sound beams) of the two printing transducers 10 coincide in space to form a confocal region 11. At this time, the confocal region 11 is larger than the focal region of a single printing transducer 10 and can be used to print blood vessel-like lumens with larger diameters.

[0093] As Figure 5 shown in (b) of [], the control module 50 controls the electric rotating shaft 23 to decrease the sound field beam angle θ between the printing transducers 10. The focal regions (the narrowest parts of the emitted sound beams) of the two printing transducers 10 coincide in space to form a confocal region 11 that is smaller than the focal region of a single printing transducer 10, and a higher printing resolution can be obtained for printing lumens with smaller diameters. During the adjustment process, the monitoring module 40 fixed at the center of the printing front end should always be aligned with the sound focus region.

[0094] Figure 6 In (a) to (c) of [], the monitoring module 40 obtains ultrasonic images through the second echo signal of the second ultrasonic wave. Figure 6 In (a) of [], it is the ultrasonic gray-scale image of the cross-section of the soft tissue phantom 100 obtained by the active scanning of the monitoring module 40 before printing, while Figure 6The ultrasound gray-scale images of the cross-sections of the lumen of the soft tissue phantom 100 in (b) and (c) are actively scanned by the post-print monitoring module 40. As can be seen from the pictures, after printing, the inner wall of the printing lumen shows a high bright gray-scale value due to strong reflection, while the gray-scale value inside the lumen decreases, showing a difference from the gray-scale value of the cross-section of the phantom 100 before printing. With the imaging position unchanged, the gray-scale value of the wall region after printing ( Figure 6 the bright region in (b) and (c)) is used as the boundary segmentation, and the gray-scale value of the inner region of the lumen before printing Figure 6 in (a) is subtracted from the gray-scale value of the inner region of the lumen after printing to obtain the gray-scale value difference between the images before and after printing, and the pixel region of the printed lumen is obtained, as shown in Figure 6 (d) and (e). On the premise of knowing the imaging depth and lateral resolution, the actual spatial size of the pixel image can be known. The size of a single pixel can be obtained by converting through the size of the image pixel data. Furthermore, the lumen size (i.e., the printing cross-sectional area) is calculated using the number of pixels in the lumen in Figure 6 (d) and (e). Whether the printing requirements are met is judged based on the lumen size and shape. If the printing requirements are not met and the pulse parameters output by the signal generator 51 are set correctly. The control module 50 adjusts the pulse emission time of the signal generator 51 and the settings of the confocal region 11, or controls the vertical and left-right movement of the confocal region 11 through the programmable numerical control robotic arm to expand the pipe diameter until the printed lumen meets the application requirements.

[0095] The key point of the three-dimensional ultrasound printing method provided by this application lies in the direct printing method. Utilizing the confocal and sonoporation effects of the high-intensity focused ultrasound transducer, an artificial blood vessel lumen is directly printed in the cured soft tissue phantom 100, greatly improving the printing efficiency. Encapsulated microbubbles can be added during printing to enhance the sonoporation effect. The core of the three-dimensional ultrasound printing system lies in introducing the confocal method. By changing the acoustic beam angle and intersection position of the confocal fields of the two transducers through the electric rotating shaft 23, etc., the shape and size of the acoustic printing area can be controlled, and blood vessel lumens of different shapes and sizes can be printed under appropriate acoustic excitation parameters, improving the printing efficiency. By moving the confocal region 11 vertically and left-right to expand the pipe diameter, artificial blood vessels with a larger cross-sectional area can be printed.

[0096] Compared with the existing indirect forming technologies, such as the indirect forming method based on the fused deposition modeling (FDM) printing technology, the three-dimensional ultrasound printing method provided by this application does not require sacrificial materials. Printing largely depends only on acoustic energy and does not produce toxic and side compounds, having high safety.

[0097] Compared with stereolithography, the three-dimensional ultrasonic printing provided by the present application has relatively controllable acoustic attenuation in the homogeneous soft tissue phantom 100, can perform remote printing in a relatively deep range (>10 mm), and the acoustic energy is focused on the confocal region 11 in space, and basically does not affect the soft tissue phantom 100 in the relatively superficial layer outside the confocal region 11, which is significantly different from the photolithography technology.

[0098] Compared with the acoustic curing forming technology that requires printing line by line, the three-dimensional ultrasonic printing method provided by the present application directly prints the vascular lumen in the cured soft tissue phantom 100, simplifies the printing process, and greatly improves the printing efficiency.

[0099] Those skilled in the art can understand that all or part of the functions of the various methods in the above embodiments can be implemented in a hardware manner or in a computer program manner. When all or part of the functions in the above embodiments are implemented in a computer program manner, the program can be stored in a computer-readable storage medium. The storage medium may include: read-only memory, random access memory, magnetic disk, optical disk, hard disk, etc. The above functions are implemented by a computer executing the program. For example, the program is stored in the memory of the device, and when the processor executes the program in the memory, the above all or part of the functions can be implemented. In addition, when all or part of the functions in the above embodiments are implemented in a computer program manner, the program can also be stored in a storage medium such as a server, another computer, magnetic disk, optical disk, flash drive or mobile hard disk, and is saved to the memory of the local device by downloading or copying, or the system of the local device is updated. When the processor executes the program in the memory, the above all or part of the functions in the above embodiments can be implemented.

[0100] This document has been described with reference to various exemplary embodiments. However, those skilled in the art will recognize that changes and modifications can be made to the exemplary embodiments without departing from the scope of this document. For example, the various operation steps and the components used to perform the operation steps can be implemented in different ways according to a specific application or considering any number of cost functions associated with the operation of the system (for example, one or more steps can be deleted, modified or combined into other steps).

[0101] Although the principles of this document have been shown in various embodiments, many modifications of the structures, arrangements, proportions, elements, materials and components that are particularly applicable to specific environments and operating requirements can be used without departing from the principles and scope of this disclosure. The above modifications and other changes or corrections will be included within the scope of this document.

[0102] The foregoing detailed description has been presented with reference to various embodiments. However, those skilled in the art will recognize that various modifications and changes can be made without departing from the scope of the disclosure. Accordingly, the contemplation of the disclosure is illustrative in nature and not restrictive, and all such modifications will be included within its scope. Similarly, the advantages, other advantages, and solutions to problems of the various embodiments have been described above. However, benefits, advantages, solutions to problems, and any elements that produce these, or that make them more explicit, should not be construed as critical, required, or essential. As used herein, the term "comprising" and any other variants thereof are non-exclusive inclusions, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but also other elements not expressly listed or inherent to the process, method, system, article, or apparatus. In addition, the term "coupled" and any other variants thereof as used herein refer to physical connection, electrical connection, magnetic connection, optical connection, communication connection, functional connection, and / or any other connection.

[0103] Those having skill in the art will recognize that many changes may be made to the details of the above-described embodiments without departing from the basic principles of the invention. Thus, the scope of the invention should be determined solely by the claims.

Claims

1. An ultrasonic printing method imitating a blood vessel network, characterized in that Comprising: Obtaining preset printing information of a blood vessel-mimicking network, where the preset printing information includes a printing path and a printing cross-sectional area corresponding to each printing site on the printing path; Determining a first cavitation intensity and a second cavitation intensity required for printing according to the phantom, and determining excitation parameters of at least two printing transducers; Adjusting the position, shape, and size of the confocal region of the at least two printing transducers according to the preset printing information; Determining that the cavitation intensity of the confocal region is greater than or equal to the first cavitation intensity and the cavitation intensity of the region other than the confocal region is less than the second cavitation intensity, and starting to print the phantom. Wherein, the phantom is slightly damaged in the confocal region to form a cavity, and no damage occurs in the region other than the confocal region; Obtaining the actual printing cross-sectional area of the current printing site. If the preset printing information is satisfied, controlling the confocal region to move to the next printing site to be printed, and adjusting the size of the confocal region according to the printing cross-sectional area required by the next printing site to be printed; if the preset printing information is not satisfied, continue printing the current printing site, and obtain the actual printing cross-sectional area of the current printing site again after a preset interval; 2. The ultrasonic printing method according to claim 1, characterized in that Before starting to print the phantom, it further includes: Determining whether the actual starting printing site meets the requirements of the starting printing site in the preset printing information; 3. The ultrasonic printing method according to claim 1, characterized in that Determining that the cavitation intensity of the confocal region is greater than or equal to the first cavitation intensity, including: Obtaining a first echo signal generated by the confocal region, processing the first echo signal to obtain the intensity of the corresponding broadband noise component, and quantifying the cavitation intensity of the confocal region with this; When the cavitation intensity is less than the first cavitation intensity, adjusting the excitation parameters of the printing transducer so that the cavitation intensity of the confocal region is greater than or equal to the first cavitation intensity, and the excitation parameters include at least one of the emission center frequency, excitation voltage, pulse duration, and pulse repetition frequency; 4. The ultrasonic printing method according to claim 3, wherein Processing the first echo signal includes: Performing spectral analysis and / or beam synthesis on the first echo signal to obtain the intensity of the corresponding broadband noise component; 5. The ultrasonic printing method according to claim 1, wherein Obtaining the actual printing cross-sectional area of the current printing site, including: Obtaining a second echo signal of a second ultrasonic signal emitted by the monitoring module, obtaining a cross-sectional image corresponding to the current printing site according to the second echo signal, and calculating the actual printing cross-sectional area of the current printing site according to the cross-sectional image; 6. The ultrasonic printing method according to claim 1, characterized in that, Adjusting the position, shape, and size of the confocal region of the at least two printing transducers, including: Adjusting the beam angles and intersection positions of the at least two printing transducers to adjust the shape and size of the confocal region; 7. An ultrasonic printing system imitating a blood vessel network, characterized in that, Comprising: At least two printing transducers, the printing transducers are used to emit a first ultrasonic signal, and the first ultrasonic signals of the at least two printing transducers form a confocal region; A first motion mechanism for driving the printing transducer to perform relative motion to adjust the shape and size of the confocal region and the first position of the confocal region relative to the first motion mechanism; A second motion mechanism for driving the first motion mechanism to move, and the printing transducer follows the first motion mechanism to move to adjust the second position of the confocal region relative to the phantom; A control module for: Obtaining preset printing information of the vascular network simulation, where the preset printing information includes a printing path and the printing cross-sectional area corresponding to each printing site on the printing path; Determining the first cavitation intensity and the second cavitation intensity required for printing according to the phantom, and determining the excitation parameters of at least two printing transducers; Adjusting the position, shape and size of the confocal region of the at least two printing transducers according to the preset printing information; Determining that the cavitation intensity of the confocal region is greater than or equal to the first cavitation intensity and the cavitation intensity of the region other than the confocal region is less than the second cavitation intensity, and starting to print the phantom, where the phantom is slightly damaged in the confocal region to form a cavity and no damage occurs in the region other than the confocal region; Obtaining the actual printing cross-sectional area of the current printing site. If the preset printing information is satisfied, controlling the confocal region to move to the next printing site to be printed, and adjusting the size of the confocal region according to the printing cross-sectional area required by the next printing site to be printed; if the preset printing information is not satisfied, continuing to print the current printing site, and obtaining the actual printing cross-sectional area of the current printing site again after a preset interval; 8. The ultrasonic printing system according to claim 7, wherein, The ultrasonic printing system further includes a monitoring module; The monitoring module is used to emit a second ultrasonic signal to the phantom and receive the second echo signal of the second ultrasonic signal; it is also used to receive the first echo signal of the first ultrasonic signal; The control module determines the actual printing cross-sectional area according to the second echo signal, and determines the cavitation intensity of the confocal region according to the first echo signal; 9. The ultrasonic printing system according to claim 8, wherein The ultrasonic printing system further includes a printing container; The printing container is used to hold a coupling agent. When the ultrasonic printing system works, the phantom is immersed in the coupling agent, and the printing transducer and the monitoring module emit ultrasonic signals to the phantom through the coupling agent; The coupling agent is added with acoustic-sensitive nanoparticles, and the acoustic-sensitive nanoparticles are used to enhance the thermal effect, sonochemical reaction or acoustic cavitation effect of the first ultrasonic signal; 10. A computer-readable storage medium, characterized in that, A program is stored on the medium, and the program can be executed by a processor to implement the method according to any one of claims 1-6.

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