A method of composite super-resolution ultrasound molecular imaging and related apparatus

Abstract

The application discloses a kind of composite super-resolution ultrasonic molecular imaging method and related equipment, belong to ultrasonic imaging technical field, by obtaining high frame rate ultrasonic contrast image and conventional ultrasonic contrast image sequence, high frame rate ultrasonic contrast image sequence is carried out super-resolution image reconstruction, obtains super-resolution blood vessel image, ultrasonic molecular imaging processing is carried out to conventional ultrasonic contrast image sequence, obtains ultrasonic molecular imaging image, to super-resolution blood vessel image and ultrasonic molecular imaging image is carried out composite super-resolution imaging processing, obtains composite super-resolution ultrasonic molecular imaging result, to the selective display of composite super-resolution ultrasonic molecular imaging result is carried out, and composite super-resolution molecular imaging parameter extraction and analysis can be simultaneously super-resolution visualized vascular structure and blood flow in imaging area and specific biomolecule or marker distribution, simultaneously obtain vascular structure information and hemodynamics and specific target distribution function information.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of ultrasonic imaging, and particularly relates to a composite super-resolution ultrasonic molecular imaging method and related equipment. BACKGROUND

[0002] Ultrasonic molecular imaging forms a targeted contrast agent by connecting an antibody or ligand specifically combined with a specific molecule or cell marker to the surface of an ultrasonic contrast agent, so that the targeted contrast agent can actively bind to a target region and selectively gather in a target tissue or target organ, and then ultrasonic contrast imaging is used to realize specific ultrasonic imaging of the specific molecule or cell marker, thereby reflecting changes occurring at the molecular and cell levels in a lesion site.

[0003] In the development process of various diseases, in addition to specific molecular level changes, changes in the morphological structure of blood vessels often occur. For example, tumor cells proliferate rapidly at the primary tumor site, and will secrete vascular endothelial growth factor and other factors that promote tumor angiogenesis. These pro-angiogenic factors promote the proliferation and migration of endothelial cells in the blood vessel wall, leading to irregular changes in the structure of the blood vessel wall, such as thickening of the blood vessel wall and narrowing of the lumen, and affecting the elasticity and compliance of the blood vessel wall, resulting in increased stiffness of the blood vessel. At the same time, it also affects the physiological function of the blood vessel. The narrowed lumen restricts blood flow and increases blood flow resistance, and the increased stiffness of the blood vessel also reduces the buffering capacity of the blood vessel to blood pressure changes, further exacerbating hemodynamic abnormalities. In addition, there are other biomarkers such as alpha v Beta 3 integrin, P-selectin and endothelin, whose overexpression promotes the growth and division of tumor endothelial cells, and ultimately forms mature tumor neovessels.

[0004] Current ultrasonic molecular imaging cannot accurately obtain the position and distribution of targets at a lesion site due to the resolution limitation of ultrasonic contrast imaging. In addition, it is not known whether the relative position relationship of these targets and the surrounding blood vessels and the microvascular structure and function have changed. In recent years, the rapidly developing super-resolution ultrasonic imaging technology can break through the resolution limitation of traditional ultrasonic imaging, and can obtain super-resolution microflow images reflecting the morphological structure of microvessels and blood flow velocity, direction, etc., but cannot reflect the molecular level reasons that may cause blood vessel abnormalities. SUMMARY

[0005] The application provides a composite super-resolution ultrasonic molecular imaging method and related equipment, which solves the problem that existing ultrasonic molecular imaging cannot accurately obtain the position and distribution of targets at a lesion site and their relative position to blood vessels.

[0006] To achieve the above object, the application provides the following technical scheme:

[0007] A composite super-resolution ultrasonic molecular imaging method comprises:

[0008] acquiring a high frame rate ultrasound contrast image sequence and a regular ultrasound contrast image sequence;

[0009] performing super-resolution image reconstruction on the high frame rate ultrasound contrast image sequence to obtain a super-resolution blood vessel image;

[0010] performing ultrasound molecular imaging processing on the regular ultrasound contrast image sequence to obtain an ultrasound molecular imaging image;

[0011] performing compound super-resolution imaging processing on the super-resolution blood vessel image and the ultrasound molecular imaging image to obtain a compound super-resolution ultrasound molecular imaging result;

[0012] performing selective display on the compound super-resolution ultrasound molecular imaging result, and extracting and analyzing a compound super-resolution molecular imaging parameter.

[0013] Preferably, the frame rate of the high frame rate ultrasound contrast image sequence is 150-300 frames per second.

[0014] Preferably, the acquisition of the high frame rate ultrasound contrast image and the regular ultrasound contrast image sequence is both based on a targeted ultrasound contrast agent, and the acquisition method is one of the following two methods:

[0015] The first method is:

[0016] acquiring the high frame rate ultrasound contrast image sequence at T1;

[0017] acquiring a first regular ultrasound contrast image sequence containing both adherent and flowing contrast agent signals at T2;

[0018] emitting a bubble-breaking pulse to destroy all contrast agents in the imaging plane at T3

[0019] acquiring a second regular ultrasound contrast image sequence containing only flowing contrast agent signals at T4;

[0020] The second method is:

[0021] acquiring the high frame rate ultrasound contrast image sequence at T1

[0022] acquiring a third regular ultrasound contrast image sequence at T5;

[0023] wherein the time interval between T1 and T2 is 3-5 minutes, the time interval between T3 and T2 is 5-10 seconds, the time interval between T4 and T3 is 20-40 seconds, and the time interval between T1 and T5 is 1-3 minutes.

[0024] Preferably, the ultrasound molecular imaging processing on the regular ultrasound contrast image sequence to obtain an ultrasound molecular imaging image is specifically:

[0025] The first and second regular ultrasound contrast image sequences are averaged respectively, and the ultrasound molecular imaging image is obtained by subtracting the first regular ultrasound contrast image average from the second regular ultrasound contrast image average.

[0026] Preferably, the regular ultrasound contrast image sequence is processed by ultrasound molecular imaging to obtain the ultrasound molecular imaging image, specifically:

[0027] The third regular ultrasound contrast image sequence is motion corrected, and the intensity value of each pixel in the image is calculated frame by frame. If the intensity value of the pixel is greater than 10%-30% of the maximum intensity value of the image, it is encoded as "1", otherwise it is encoded as "0";

[0028] The third regular contrast image sequence is encoded and superimposed to obtain the ultrasound molecular imaging image.

[0029] Preferably, the diameter of the targeted ultrasound contrast agent is in the range of 1-10 microns.

[0030] Preferably, the high-frame-rate ultrasound contrast image sequence is processed by super-resolution image reconstruction, specifically:

[0031] The ROI is selected on the high-frame-rate contrast image, and the contrast agent center position is determined frame by frame using the contrast agent positioning processing technology. The contrast agent position of the entire high-frame-rate contrast image sequence is motion corrected, tracked and screened, and finally the microbubble trajectory, blood flow velocity or direction is superimposed to form a super-resolution blood vessel image. The super-resolution blood vessel image includes a super-resolution blood vessel structure image, a super-resolution blood flow velocity image and a super-resolution blood flow direction image, etc.

[0032] Preferably, the composite super-resolution imaging processing is specifically:

[0033] On the ultrasound molecular imaging image, the same ROI as the super-resolution blood vessel image reconstruction is selected, and the adhesion contrast agent in the ROI is positioned using the contrast agent positioning processing technology to obtain the center position coordinates of the adhesion contrast agent.

[0034] A distance threshold is set, and the distance between each adhesion contrast agent center and the nearest blood vessel in the super-resolution blood vessel image is calculated. If the distance is less than or equal to the distance threshold, the adhesion contrast agent signal is retained; otherwise, the adhesion contrast agent is discarded to obtain a super-resolution molecular target distribution image.

[0035] The retained adhesion contrast agent center position is plotted on the super-resolution blood vessel image to obtain a composite super-resolution ultrasound molecular imaging result.

[0036] Preferably, the selective display of the composite super-resolution ultrasound molecular imaging result is specifically that the composite super-resolution ultrasound molecular imaging result can be selected to display the super-resolution blood vessel image, the super-resolution molecular target distribution image or the composite super-resolution ultrasound molecular imaging result respectively.

[0037] The composite super-resolution molecular imaging parameter extraction and analysis is specifically that the blood vessel diameter, the blood vessel density, the blood vessel tortuosity, the molecular target density, the molecular target blood vessel relative density and other composite super-resolution molecular imaging parameters in the region to be analyzed are extracted on the image and analyzed.

[0038] A composite super-resolution ultrasound molecular imaging system comprises:

[0039] An image acquisition module: acquiring a high-frame-rate ultrasound contrast image sequence and a conventional ultrasound contrast image sequence;

[0040] A super-resolution reconstruction module: performing super-resolution image reconstruction on the high-frame-rate ultrasound contrast image sequence to obtain a super-resolution blood vessel image;

[0041] A molecular imaging module: performing ultrasound molecular imaging processing on the conventional ultrasound contrast image sequence to obtain an ultrasound molecular imaging image;

[0042] A composite super-resolution imaging module: performing composite super-resolution imaging processing on the super-resolution blood vessel image and the ultrasound molecular imaging image to obtain a composite super-resolution ultrasound molecular imaging result;

[0043] A display and analysis module: selectively displaying the composite super-resolution ultrasound

[0044] molecular imaging result, and extracting and analyzing the composite super-resolution molecular imaging parameters.

[0045] A computer device comprises a memory, a processor and a computer program stored in the memory and executable on the processor, and the processor implements the steps of a composite super-resolution ultrasound molecular imaging method when executing the computer program.

[0046] The computer readable storage medium stores a computer program, and the computer program is executed by a processor to implement the steps of the composite super-resolution ultrasound molecular imaging method. Compared with the prior art, the present application has the following beneficial effects: the present application provides a composite super-resolution ultrasound molecular imaging method, by acquiring a high-frame-rate ultrasound contrast image and a conventional ultrasound contrast image sequence, performing super-resolution image reconstruction on the high-frame-rate ultrasound contrast image sequence to obtain a super-resolution blood vessel image, performing ultrasound molecular imaging processing on the conventional ultrasound contrast image sequence to obtain an ultrasound molecular imaging image, performing composite super-resolution imaging processing on the super-resolution blood vessel image and the ultrasound molecular imaging image to obtain a composite super-resolution ultrasound molecular imaging result, and performing selective display on the composite super-resolution ultrasound molecular imaging result, and performing composite super-resolution molecular imaging parameter extraction and analysis, the blood vessel structure and blood flow in the imaging area and the distribution of specific biomolecules or markers can be simultaneously visualized in a super-resolution manner, and the vascular structure information and functional information such as blood flow dynamics and specific target distribution can be obtained. BRIEF DESCRIPTION OF DRAWINGS

[0047] Figure 1 The flowchart of the composite super-resolution ultrasound molecular imaging method of the present application.

[0048] Figure 2 The flowchart of the composite super-resolution ultrasound molecular imaging method provided by the embodiment of the present application.

[0049] Figure 3 The timing diagram of the ultrasound imaging and bubble-breaking pulses according to the first embodiment of the present application.

[0050] Figure 4 The timing diagram of the ultrasound imaging pulses according to the second embodiment of the present application.

[0051] Figure 5 The optical microscope observation result of the targeted ultrasound contrast agent of embodiment 1 of the present application, (scale bar = 20 μm).

[0052] Figure 6 The composite super-resolution ultrasound molecular imaging result of embodiment 1 of the present application, wherein (a) is a super-resolution blood vessel structure image, (b) is a super-resolution blood flow velocity image, (c) is an ultrasound molecular imaging image, and (d) is a composite super-resolution ultrasound molecular imaging result.

[0053] Figure 7 The composite super-resolution ultrasound molecular imaging result of embodiment 2 of the present application, wherein (a) is a super-resolution blood vessel image, (b) is an ultrasound molecular imaging image, (c) is a composite super-resolution ultrasound molecular imaging result, and (d) is a molecular target blood vessel relative density parameter.

[0054] Figure 8A composite super-resolution ultrasound molecular imaging system block diagram of the present application. DETAILED DESCRIPTION

[0055] For the purposes of making the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are some but not all of the embodiments of the present application. The components of the embodiments of the present application described and shown in the drawings herein can be arranged and designed in various different configurations.

[0056] Therefore, the following detailed description of the embodiments of the present application provided in the drawings is not intended to limit the scope of the claimed present application, but only represents selected embodiments of the present application. All other embodiments obtained by a person of ordinary skill in the art without creative labor based on the embodiments in the present application are within the scope of protection of the present application.

[0057] As Figure 1 The present application provides a composite super-resolution ultrasound molecular imaging method, comprising:

[0058] S101 acquiring a high-frame-rate ultrasound contrast image and a conventional ultrasound contrast image sequence;

[0059] S102 performing super-resolution image reconstruction on the high-frame-rate ultrasound contrast image sequence to obtain a super-resolution blood vessel image;

[0060] S103 performing ultrasound molecular imaging processing on the conventional ultrasound contrast image sequence to obtain an ultrasound molecular imaging image;

[0061] S104 performing composite super-resolution imaging processing on the super-resolution blood vessel image and the ultrasound molecular imaging image result to obtain a composite super-resolution ultrasound molecular imaging result;

[0062] S105 performing selective display on the composite super-resolution ultrasound molecular imaging result, and performing composite super-resolution molecular imaging parameter extraction and analysis.

[0063] Specifically as Figure 2 The present application provides a composite super-resolution ultrasound molecular imaging method, comprising the following steps:

[0064] S1 intravenous injection of a targeted ultrasound contrast agent, the diameter of the targeted ultrasound contrast agent being in the range of 1-10 microns;

[0065] S2 emitting an ultrafast contrast imaging pulse at T1 to obtain an N1-frame high-frame-rate ultrasound contrast image sequence;

[0066] S3 emits a regular contrast imaging pulse at T2, and acquires a sequence of N2 frames of regular ultrasound contrast images;

[0067] S4 emits a high acoustic pressure bubble breaking pulse at T3, and emits a regular contrast imaging pulse again at T4, and acquires a sequence of N3 frames of regular ultrasound contrast images; a timing diagram of ultrasound imaging pulse emission is shown in Figure 3

[0068] S5 performs super-resolution image reconstruction on the acquired sequence of N1 frames of high frame rate ultrasound contrast images, and obtains a super-resolution blood vessel image;

[0069] S6 performs first ultrasound molecular imaging processing on the acquired sequence of N2 frames and N3 frames of regular ultrasound contrast images, and obtains an ultrasound molecular imaging image;

[0070] S7 performs composite super-resolution imaging processing on the super-resolution blood vessel image and the ultrasound molecular imaging image, and obtains a composite super-resolution ultrasound molecular imaging result;

[0071] S8 performs selective display on the composite super-resolution ultrasound molecular imaging result, and performs composite super-resolution molecular imaging parameter extraction and analysis.

[0072] As shown in Figure 2 Another embodiment of the present application provides a composite super-resolution ultrasound molecular imaging method based on a targeted ultrasound contrast agent, and the method comprises the following steps:

[0073] S1' intravenously injects a targeted ultrasound contrast agent;

[0074] S2' emits an ultrafast contrast imaging pulse at T1, and acquires a sequence of N1 frames of high frame rate ultrasound contrast images;

[0075] S3' emits a regular contrast imaging pulse at T5, and acquires a sequence of N4 frames of regular ultrasound contrast images; a timing diagram of ultrasound imaging pulse emission is shown in Figure 4

[0076] S4' performs super-resolution image reconstruction on the acquired sequence of N1 frames of high frame rate ultrasound contrast images, and obtains a super-resolution blood vessel image;

[0077] S5' performs second ultrasound molecular imaging processing on the sequence of N4 frames of regular ultrasound contrast images, and obtains an ultrasound molecular imaging image;

[0078] S6' performs composite super-resolution imaging processing on the super-resolution blood vessel image and the ultrasound molecular imaging image, and obtains a composite super-resolution ultrasound molecular imaging result;

[0079] ​​S7' selectively displays the composite super-resolution ultrasound molecular imaging result, and performs composite super-resolution molecular imaging parameter extraction and analysis.

[0080] The membrane material of the targeted contrast agent includes phospholipids, proteins, sugars and polymers, etc., and the target of the targeted contrast agent includes cell surface receptors, tumor markers, vascular markers, tissue-specific antigens, etc.

[0081] The superfast contrast imaging pulse is a composite plane wave pulse sequence, and the conventional contrast imaging pulse is a focused wave pulse sequence; the frame rate of the high-frame-rate ultrasound contrast image sequence is 150-300 frames / s, preferably no less than 150 frames / s, more preferably 200-300 frames / s; the frame rate of the conventional ultrasound contrast image sequence is 10-25 frames / s.

[0082] T1 is preferably 30 seconds-2 minutes after injection of the targeted ultrasound contrast agent, and the N1 frame high-frame-rate ultrasound contrast image sequence is preferably 1000-2000 frames.

[0083] T2 is preferably 4-6 minutes after injection of the targeted ultrasound contrast agent, T3 is preferably 5-10 seconds after T2, and T4 is usually 20-40 seconds after T3; the N2 frame conventional ultrasound contrast image sequence is preferably 40-80 frames, and the N3 frame conventional ultrasound contrast image sequence is preferably 40-80 frames.

[0084] T5 is usually greater than the peak time of the perfusion time intensity curve and less than the time corresponding to the intensity dropping to half of the peak value, and is preferably 3-5 minutes after injection of the targeted ultrasound contrast agent; the N4 frame conventional ultrasound contrast image sequence is preferably 200-300 frames.

[0085] The step of super-resolution image reconstruction includes: ROI on the N1 frame high-frame-rate contrast image, determining the contrast agent center position by frame using the contrast agent positioning processing technology, and then performing motion correction, tracking and screening on the contrast agent positions of the entire N1 frame high-frame-rate contrast image sequence, and finally superimposing the microbubble trajectory, flow velocity and direction to form the super-resolution blood vessel image, which includes super-resolution blood vessel structure image, super-resolution blood flow velocity image and super-resolution blood flow direction image, etc.

[0086] The first ultrasound molecular imaging processing includes the following steps: performing motion correction on the N2 frame and N3 frame conventional ultrasound contrast image sequences, and then averaging the corrected N2 frame and N3 frame contrast images, respectively, subtracting the N2 frame image average from the N3 frame image average and selecting a suitable threshold to obtain the ultrasound molecular imaging image.

[0087] The second ultrasound molecular imaging processing includes the following steps:

[0088] S21 motion correction is performed on the N4 frame of the conventional ultrasound contrast image sequence, and the intensity value of each pixel is calculated frame by frame. If the intensity value of the pixel is greater than 10-30%, preferably 20%, of the maximum intensity value of the image, it is encoded as "1", otherwise it is encoded as "0".

[0089] S22 encodes and superimposes the N4 frame of the conventional ultrasound contrast image sequence, retains the adherent contrast agent signal at the pixel position where the total sum of the encoding values is greater than or equal to N4x(60-80%), preferably retains the adherent contrast agent signal at the pixel position where the total sum of the encoding values is greater than or equal to N4x80%, and sets the signal at the remaining pixel positions to zero to obtain an ultrasound molecular imaging image.

[0090] The composite super-resolution imaging processing includes the following steps:

[0091] S31 selects the same ROI region as the super-resolution blood vessel image reconstruction on the ultrasound molecular imaging image, and uses a contrast agent positioning processing technique to locate the adherent contrast agent in the image to obtain the center position coordinates of the adherent contrast agent;

[0092] S32 calculates the distance d between the center position of each adherent contrast agent and the nearest blood vessel in the super-resolution blood vessel image. If the distance d is less than or equal to the distance threshold d0, the adherent contrast agent signal is retained; otherwise, the adherent contrast agent is discarded.

[0093] S33 plots the center position of the adherent contrast agent on the super-resolution blood vessel image to obtain a composite super-resolution ultrasound molecular imaging result.

[0094] The distance threshold d0 is usually less than 500 microns, preferably 300 microns.

[0095] The contrast agent positioning processing technique includes point spread function (PSF) deconvolution method, centroid method, Gaussian fitting method, peak positioning method, etc.

[0096] The composite super-resolution molecular imaging parameters include blood vessel diameter, blood vessel density, blood vessel tortuosity, molecular target surface density, and molecular target blood vessel relative density.

[0097] Example 1: Composite super-resolution ultrasound molecular imaging of a breast cancer mouse model based on VEGFR2-targeted microbubbles

[0098] A 4T1 breast cancer subcutaneous tumor model was established in 6-8 week old female BALB / C mice. When the tumor volume reached 80-100 mm 3 left and right when the imaging experiment was performed.

[0099] The tumor-bearing mice were fixed on a heating pad and continuously anesthetized with 2% (mass percentage) isoflurane. The tumor area of the mice was depilated and the ultrasonic coupling agent was applied on the skin. The probe was fixed to maintain the imaging section unchanged.

[0100] Targeted microbubbles MB targeting VEGFR2, a factor related to angiogenesis VEGFR2 The results of observation under an optical microscope (as shown in Figure 5 The microbubbles MB targeting VEGFR2 were diluted to 5×10 8 μL with a phosphate buffer solution (PBS) to 5×10

[0101] The ultrafast contrast imaging was performed 30 seconds after the injection of the microbubbles (at a frame rate of 200 frames / s) to obtain 2000 frames of high-frame-rate contrast images.

[0102] The regular contrast imaging was performed 6 minutes after the injection of the microbubbles (at a frame rate of 10 frames / s) to obtain 50 frames of regular contrast images.

[0103] Then, a high-sound-pressure bubble destruction pulse was emitted to destroy all the microbubbles in the plane.

[0104] The regular contrast imaging was continued 20 seconds later to obtain 50 frames of regular contrast images.

[0105] The center position of the contrast agent was located frame by frame on the 2000 frames of high-frame-rate contrast images by using the radial symmetry method, and the trajectory of the center position of the contrast agent in the 2000 frames of high-frame-rate contrast images was tracked. Finally, the microbubble trajectory and velocity were superimposed and displayed to obtain the images of the ultraresolved blood vessel structure and blood flow velocity, as shown in Figure 6 (a) and (b), respectively.

[0106] The motion correction was performed on the obtained 100 frames of regular contrast images. Then, the corrected contrast images of the first 50 frames and the last 50 frames were averaged, respectively. The average image of the first 50 frames was subtracted from the average image of the last 50 frames, and a suitable threshold value was selected to obtain the ultrasound molecular imaging image, as shown in Figure 6 (c).

[0107] The center position of each adherent contrast agent was located by using the center of mass method in Figure 6 (c) to obtain the coordinate of the center position of each adherent contrast agent. The distance value d from the center position of each adherent contrast agent to the nearest blood vessel in the ultraresolved blood vessel image was calculated. If the distance value d was less than or equal to 300 μm, the adherent contrast agent signal was retained. If the distance value d was greater than 300 μm, the adherent contrast agent was discarded. The center position of the retained adherent contrast agent was marked with a blue asterisk (*) and plotted on the ultraresolved blood vessel image to obtain the composite ultraresolved ultrasound molecular imaging result, as shown in Figure 6 (d).

[0108] Example 2 Composite super-resolution ultrasound molecular imaging of breast cancer model based on B7-H3-targeted microbubbles,

[0109] The 4T1 breast cancer subcutaneous tumor model was established in 6-8 weeks old female BALB / C mice, and the imaging experiment was performed when the tumor volume reached about 80-100 mm3.

[0110] The tumor-bearing mice were fixed on a heating pad and continuously anesthetized with isoflurane at a concentration of 2% (mass percent), the tumor area of the mice was depilated, and the ultrasonic coupling agent was applied to the skin, and the probe was fixed to maintain the imaging section unchanged.

[0111] Targeted microbubbles MB B7-H3 Diluted to 5x10 8 μL by tail vein injection into the mouse for imaging.

[0112] Ultrasonic imaging was performed 30 seconds after injection of microbubbles (frame rate of 200 frames / s), and 2000 frames of high-frame-rate contrast images were obtained.

[0113] Regular contrast-enhanced ultrasound imaging was performed 3 minutes and 30 seconds after injection of microbubbles, and 200 frames of regular contrast-enhanced ultrasound images were obtained.

[0114] The radial symmetry method was used to locate the center position of the contrast agent frame by frame for the obtained 2000 frames of high-frame-rate contrast images, and the position of the contrast agent in all 2000 frames of high-frame-rate contrast images was motion corrected and tracked. Finally, all microbubble tracks were superimposed to obtain a super-resolution blood vessel image, as shown in Figure 7 (a).

[0115] The motion correction was performed on the obtained 200 frames of regular contrast-enhanced ultrasound images, and the intensity value of each pixel was calculated frame by frame. If the intensity value of the pixel is greater than 20% of the maximum intensity value of the image, it is encoded as "1", otherwise it is encoded as "0". Then the 200 frames of regular contrast-enhanced ultrasound images are encoded and superimposed to sum, and the adherent contrast agent signal at the pixel position where the total sum of the encoding value is greater than or equal to 160 is retained, and the signals at the remaining pixel positions are set to zero, to obtain an ultrasound molecular imaging image, as shown in Figure 7 (b).

[0116] The centroid method was used to track the Figure 7(b) is positioned to obtain the center position coordinates of each adhesion contrast agent; the distance value d of the center position of each adhesion contrast agent to the nearest blood vessel in the super-resolution blood vessel image is calculated, if the distance value d is less than or equal to 300 μm, the adhesion contrast agent signal is retained; the adhesion contrast agent is discarded. The adhesion contrast agent is marked with a blue asterisk (*) and drawn on the super-resolution blood vessel image to obtain a composite super-resolution ultrasound molecular imaging result, such as Figure 7 (c).

[0117] In the super-resolution blood vessel image, the ratio of the number of molecular targets in the selected tumor region to the pixel area of the super-resolution blood vessel part is calculated to obtain the relative density of molecular targets and blood vessels of the tumor and tissue, such as Figure 7 (d).

[0118] The composite super-resolution ultrasound molecular imaging method of the present application can visualize the vascular network structure information and functional information such as blood flow and specific marker distribution at one time with super-resolution, so as to realize simultaneous and efficient imaging of the structure information at the vascular level and the functional information at the molecular level. This method helps researchers to accurately obtain the target position and distribution of the lesion site and explore the relative relationship between the molecular target and the surrounding blood vessels, etc. Deep mechanism, which provides an important information basis for developing more accurate treatment strategies. This not only can improve the understanding of the development mechanism of the disease, but also can provide more accurate reference index for early lesion positioning and detection of specific biomarkers, which is expected to provide more accurate and effective means for diagnosis and treatment of diseases.

[0119] As shown in Figure 8 The present application also provides a composite super-resolution ultrasound molecular imaging system, comprising:

[0120] An image acquisition module: acquiring a high-frame-rate ultrasound contrast image group and a conventional ultrasound contrast image group;

[0121] A super-resolution reconstruction module: performing super-resolution image reconstruction on the high-frame-rate ultrasound contrast image group to obtain a super-resolution blood vessel image;

[0122] A molecular imaging module: performing ultrasound molecular imaging processing on the conventional ultrasound contrast image group to obtain an ultrasound molecular imaging image;

[0123] A composite super-resolution imaging module: performing composite super-resolution imaging processing on the super-resolution blood vessel image and the ultrasound molecular imaging image to obtain a composite super-resolution ultrasound molecular imaging result;

[0124] A display and analysis module: selectively displaying the composite super-resolution ultrasound molecular imaging result, and extracting and analyzing the composite super-resolution molecular imaging parameters.

[0125] An embodiment of the present invention provides a terminal device. This terminal device includes a processor, a memory, and a computer program stored in the memory and executable on the processor. When the processor executes the computer program, it implements the steps in the various method embodiments described above. Alternatively, when the processor executes the computer program, it implements the functions of each module / unit in the various device embodiments described above.

[0126] The computer program can be divided into one or more modules / units, which are stored in the memory and executed by the processor to complete the present invention.

[0127] The terminal device may be a desktop computer, laptop, handheld computer, or cloud server, etc. The terminal device may include, but is not limited to, a processor and a memory.

[0128] The processor may be a central processing unit (CPU), or other general-purpose processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc.

[0129] The memory can be used to store the computer program and / or module. The processor implements various functions of the terminal device by running or executing the computer program and / or module stored in the memory and calling the data stored in the memory.

[0130] If the modules / units integrated into the terminal device are implemented as software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on this understanding, all or part of the processes in the methods of the above embodiments can also be implemented by a computer program instructing related hardware. The computer program can be stored in a computer-readable storage medium, and when executed by a processor, it can implement the steps of the various method embodiments described above. The computer program includes computer program code, which can be in the form of source code, object code, executable files, or certain intermediate forms. The computer-readable medium can include: any entity or device capable of carrying the computer program code, recording media, USB flash drives, portable hard drives, magnetic disks, optical disks, computer memory, read-only memory (ROM), random access memory (RAM), electrical carrier signals, telecommunication signals, and software distribution media, etc. It should be noted that the content included in the computer-readable medium can be appropriately added or removed according to the requirements of legislation and patent practice in the jurisdiction. For example, in some jurisdictions, according to legislation and patent practice, computer-readable media do not include electrical carrier signals and telecommunication signals.

[0131] Although embodiments of the present invention have been described above in conjunction with the accompanying drawings, the present invention is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art, guided by the specification, can make many other modifications without departing from the scope of the claims of the present invention, and all of these modifications are within the scope of protection of the present invention.

Claims

1. A composite super-resolution ultrasound molecular imaging method, characterized in that, include: Acquire high frame rate ultrasound contrast images and conventional ultrasound contrast image sequences; Super-resolution vascular images are obtained by reconstructing high frame rate ultrasound contrast images. Ultrasonic molecular imaging images are obtained by performing ultrasonic molecular imaging processing on conventional ultrasound contrast imaging image sequences. Composite super-resolution ultrasound molecular imaging results are obtained by performing composite super-resolution vascular images and ultrasound molecular imaging results on the super-resolution vascular images and ultrasound molecular imaging results. Selective display of composite super-resolution ultrasound molecular imaging results, and extraction and analysis of composite super-resolution molecular imaging parameters; The composite super-resolution imaging process specifically includes: On the ultrasound molecular imaging image, the same ROI as the super-resolution vascular image is selected, and the adhesive contrast agent in the ROI is located using contrast agent localization processing technology to obtain the center position coordinates of the adhesive contrast agent. A distance threshold is set, and the distance between each adhesive contrast agent center and the nearest vessel in the super-resolution vascular image is calculated. If the distance is less than or equal to the distance threshold, the adhesive contrast agent signal is retained; otherwise, the adhesive contrast agent is discarded, and a super-resolution molecular target distribution image is obtained. The center position of the retained adhesive contrast agent is plotted on the super-resolution vascular image to obtain the composite super-resolution ultrasound molecular imaging result.

2. The composite super-resolution ultrasound molecular imaging method according to claim 1, characterized in that, The high frame rate ultrasound contrast imaging sequence has a frame rate of 150-300 frames per second.

3. The composite super-resolution ultrasound molecular imaging method according to claim 1, characterized in that, Both high-frame-rate ultrasound contrast imaging and conventional ultrasound contrast imaging sequences are acquired based on targeted ultrasound contrast agents, using the following two methods: The first type is: Acquire a high frame rate ultrasound contrast imaging sequence at time T1; Acquire a first conventional ultrasound contrast imaging sequence containing signals of adhering and flowing contrast agent at time T2; At time T3, a bubble-breaking pulse is emitted to destroy all contrast agents within the imaging plane; A second conventional ultrasound contrast imaging sequence containing only the flowing contrast agent signal was acquired at time T4; The second type is: Acquire a high frame rate ultrasound contrast imaging sequence at time T1; Acquire the third conventional ultrasound contrast imaging sequence at time T5; The time interval between T1 and T2 is 3-5 minutes, the time interval between T3 and T2 is 5-10 seconds, the time interval between T4 and T3 is 20-40 seconds, and the time interval between T1 and T5 is 1-3 minutes.

4. The composite super-resolution ultrasound molecular imaging method according to claim 3, characterized in that, The specific steps for processing conventional ultrasound contrast imaging sequences with ultrasound molecular imaging to obtain ultrasound molecular imaging images are as follows: The motion-corrected first and second conventional ultrasound contrast imaging sequences were averaged respectively, and the average of the first and second conventional ultrasound contrast imaging sequences was subtracted to obtain the ultrasound molecular imaging image.

5. The composite super-resolution ultrasound molecular imaging method according to claim 3, characterized in that, The specific steps for processing conventional ultrasound contrast imaging sequences with ultrasound molecular imaging to obtain ultrasound molecular imaging images are as follows: Motion correction is performed on the third conventional ultrasound contrast image sequence, and then the intensity value of each pixel on the image is calculated frame by frame. If the intensity value of a pixel is greater than 10%-30% of the maximum intensity value of the image, it is encoded as "1"; otherwise, it is encoded as "0". The third conventional ultrasound contrast image sequence is encoded, superimposed, and summed. A threshold is set to 60-80% of the total number of frames in the third conventional ultrasound contrast image sequence. The signals at pixel positions where the sum of the encoded values ​​is greater than or equal to the threshold are retained as the adhesion contrast agent signals, and the signals at the remaining pixel positions are set to zero to obtain an ultrasound molecular imaging image.

6. The composite super-resolution ultrasound molecular imaging method according to claim 3, characterized in that, The diameter of the targeted ultrasound contrast agent is in the range of 1-10 micrometers.

7. The composite super-resolution ultrasound molecular imaging method according to claim 1, characterized in that, The specific steps for super-resolution image reconstruction of high frame rate ultrasound contrast imaging sequences are as follows: In high frame rate contrast images, ROIs are selected, and contrast agent localization processing technology is used frame by frame to determine the center position of the contrast agent. Then, motion correction, tracking and filtering are performed on the contrast agent position of the entire high frame rate contrast image sequence. Finally, microbubble trajectories, blood flow velocity or direction are superimposed to form super-resolution vascular images. Super-resolution vascular images include super-resolution vascular structure images, super-resolution blood flow velocity images and super-resolution blood flow direction images.

8. The composite super-resolution ultrasound molecular imaging method according to claim 1, characterized in that, The selective display of the composite super-resolution ultrasound molecular imaging results specifically refers to: displaying super-resolution vascular images, super-resolution molecular target distribution images, or composite super-resolution ultrasound molecular imaging results respectively.

9. The composite super-resolution ultrasound molecular imaging method according to claim 1, characterized in that, The specific steps for extracting and analyzing parameters of composite super-resolution molecular imaging are as follows: extracting and analyzing the blood vessel diameter, blood vessel density, blood vessel tortuosity, molecular target density, and molecular target blood vessels in the region to be analyzed from the image.

10. A composite super-resolution ultrasound molecular imaging system, characterized in that, A composite super-resolution ultrasound molecular imaging method according to any one of claims 1-9 includes: Image acquisition module: Acquires high frame rate ultrasound contrast images and conventional ultrasound contrast image sequences; Super-resolution reconstruction module: Performs super-resolution image reconstruction on high frame rate ultrasound contrast imaging image sequences to obtain super-resolution vascular images; Molecular imaging module: Performs ultrasound molecular imaging processing on conventional ultrasound contrast imaging image sequences to obtain ultrasound molecular imaging images; Composite super-resolution imaging module: Performs composite super-resolution imaging processing on super-resolution vascular images and ultrasound molecular imaging images to obtain composite super-resolution ultrasound molecular imaging results; Display and Analysis Module: Selectively displays the results of composite super-resolution ultrasound molecular imaging and extracts and analyzes composite super-resolution molecular imaging parameters.

11. A computer device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that, When the processor executes the computer program, it implements the steps of the composite super-resolution ultrasound molecular imaging method as described in any one of claims 1 to 9.

12. A computer-readable storage medium storing a computer program, characterized in that, When the computer program is executed by the processor, it implements the steps of the composite super-resolution ultrasound molecular imaging method as described in any one of claims 1 to 9.

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