Ultrasonic imaging method and system for observing target area aggregation of targeted contrast agent in real time

Abstract

The invention relates to the field of medical imaging, in particular to an ultrasonic imaging method and system for observing target area aggregation of a targeted contrast agent in real time. The method comprises the following steps: injecting a contrast agent containing targeting molecules into a target area, and scanning and screening by adopting a specific ultrasonic pulse sequence to only obtain an echo signal of the contrast agent; further processing the ultrasonic echo signal by using a signal decomposition technique to extract a contrast agent signal specifically bound to the tissue target; and finally, monitoring the intensity change characteristics of the specific binding contrast agent signal in a slow time direction in real time by applying a quantitative algorithm, and taking the characteristics as a comparison basis to realize molecular targeting imaging. The ultrasonic imaging method provided by the invention overcomes the defect that the traditional ultrasonic molecular imaging method cannot realize real-time observation of target region aggregation of the targeted contrast agent, and can be more accurately applied to early diagnosis of various diseases such as cardiovascular diseases and tumors and real-time monitoring of molecular level.

Description

Technical Field

[0001] The present invention relates to the field of medical imaging, and particularly to an ultrasonic imaging method and system for real-time observation of the aggregation of targeted contrast agents in the target area. Background Art

[0002] In the field of medical imaging, ultrasonic imaging, as a non-invasive and real-time diagnostic tool, is widely used in the detection and evaluation of various diseases. However, traditional ultrasonic imaging techniques have certain limitations in observing the microscopic structure and function of specific tissues or lesion areas. Especially for the changes at the microvascular and molecular levels, their detection sensitivity and resolution often fail to meet the clinical requirements.

[0003] To overcome this challenge, researchers have developed targeted contrast agents that bind to diseased tissues or cells through specific targeting molecules, and then achieve targeted imaging of the target area through ultrasonic molecular imaging techniques. However, current ultrasonic molecular imaging techniques, such as delayed imaging method and burst reperfusion imaging method, generally rely on long-term observation or complex post-processing steps. Although these methods can reflect the molecular signals of targeted contrast agents to a certain extent, they are limited to the description of the state in a single dimension and are difficult to reflect the multi-dimensional key information such as the targeting efficiency, targeting speed, accumulation position, and accumulation density of targeted contrast agents in the target area in real time. Therefore, the presented ultrasonic molecular imaging effect also fails to meet the requirements for dynamic and highly time-effective monitoring of targeted contrast agents. At the same time, the interference of motion artifacts, background noise, and free microbubbles will also affect the accuracy and sensitivity of imaging. This situation highlights the importance of urgently exploring and developing an ultrasonic imaging method for real-time observation of the aggregation of targeted contrast agents in the target area. Summary of the Invention

[0004] To overcome the above challenges, the present invention proposes an ultrasonic imaging method and system for real-time observation of the aggregation of targeted contrast agents in the target area. By applying a specific ultrasonic pulse sequence, processing the ultrasonic echo signal using a signal decomposition method, and performing post-processing using a special calculation method, etc., the extraction and monitoring of the adhesion signal of the targeted contrast agent in the slow time direction are realized. Compared with traditional imaging techniques, the present invention not only improves the detection sensitivity and resolution of the signal, but more importantly, it can reflect the multi-dimensional aggregation and accumulation of the targeted contrast agent in the target area in a highly time-effective manner within a short time after the injection of the contrast agent, thereby achieving true real-time ultrasonic molecular imaging.

[0005] In the present invention, the targeted contrast agent is formed by connecting specific targeting molecules to the surface of an acoustic contrast agent. Depending on the specific interaction between antigen-antibody or ligand-receptor, it accumulates in specific target organs or tissues through blood circulation. By detecting the targeted contrast agent specifically bound to the target, the recognition of the target can be achieved; in addition, by quantitatively analyzing the signal intensity of the specific binding, the specific state of the target can be evaluated.

[0006] Specifically, in the present invention, first, for the distribution of the contrast agent containing targeting molecules in the target area, a specific ultrasonic pulse sequence A is applied to scan the target area. The design purpose of the pulse sequence A is to suppress tissue signals and enhance the echo signals of the targeted contrast agent, thereby improving the signal contrast. The pulse sequence A can select one or a combination of the following several imaging modes, including but not limited to a pulse phase modulation fundamental wave imaging sequence, a pulse phase modulation harmonic imaging sequence, a pulse amplitude modulation fundamental wave imaging sequence, and a pulse amplitude modulation harmonic imaging sequence. Specifically, the pulse phase modulation fundamental wave imaging sequence refers to emitting two or more ultrasonic pulses with the same frequency, the same amplitude, and different phases, and obtaining an ultrasonic image by calculating the fundamental wave component; the pulse phase modulation harmonic imaging sequence refers to emitting two or more ultrasonic pulses with the same frequency, the same amplitude, and different phases, and obtaining an ultrasonic image by calculating the harmonic component; the pulse amplitude modulation fundamental wave imaging sequence refers to emitting two or more ultrasonic pulses with the same frequency, the same phase, and different amplitudes, and obtaining an ultrasonic image by calculating the fundamental wave component; the pulse phase modulation fundamental wave imaging sequence refers to emitting two or more ultrasonic pulses with the same frequency, the same phase, and different replicas, and obtaining an ultrasonic image by calculating the harmonic component.

[0007] Secondly, the ultrasonic echo signal S1 obtained from the target area is processed. Using the signal decomposition method B, the echo signal is decomposed into different categories to highlight the characteristic signal of the targeted contrast agent. The signal decomposition method B processes the signal in the slow time direction and extracts the adhesion signal S2 and the random fluctuation signal S3 in real time. Among them, the adhesion signal S2 is the characteristic signal of the targeted contrast agent, reflecting the gradual accumulation process of the contrast agent in the target area; the random fluctuation signal S3 mainly includes the characteristics of non-target microbubbles and noise signals, reflecting unstable interference components. The specific implementation of signal decomposition is matrix tensor decomposition. According to a preferred embodiment, the singular value decomposition method is used to divide the signal into the adhesion signal S2 and the random fluctuation signal S3. Among them, the adhesion signal S2 represents the characteristic signal of the targeted contrast agent, while the random fluctuation signal S3 corresponds to the dynamic components of noise or non-target microbubbles. Through this method, the stability and accuracy of the targeted contrast agent signal can be significantly enhanced, while reducing the interference of random noise on imaging.

[0008] Next, by analyzing the temporal dynamic characteristics of the adhesion signal S2 pixel by pixel, a real-time quantitative assessment of the aggregation of the targeted contrast agent is achieved. The characteristic parameters include, but are not limited to, time to peak, maximum growth rate, enhanced area, enhanced area density, kinetic parameters, etc. Specifically, the time to peak is the time point when the signal S2 reaches its maximum intensity; the maximum growth rate is the peak growth rate of the signal S2 within a short period, reflecting the aggregation rate of the contrast agent; the enhanced area is the calculated coverage area of the targeted contrast agent in the target area, reflecting the enrichment degree; the enhanced area density is the distribution density of the targeted contrast agent per unit area, further improving the analysis accuracy; the kinetic parameters include, but are not limited to, the rate constant, half-saturation constant, and entropy of signal enhancement. Among them, entropy, as a non-linear kinetic parameter, is used to quantify the regularity and unpredictability of time series fluctuations, reflecting the possibility of new information occurring in the time series. The more complex the time, the larger the corresponding entropy value. By calculating the above parameters, a real-time, accurate, and multi-dimensional quantitative analysis of the dynamic aggregation process of the targeted contrast agent in the target tissue can be achieved, providing a reliable basis for the evaluation of diagnosis and targeted treatment effects.

[0009] Finally, the ultrasonic imaging electronic device for real-time observing the aggregation of the targeted contrast agent in the target area includes a processor and a storage medium; wherein, the processor is used to execute the computer program corresponding to the ultrasonic imaging method for real-time observing the aggregation of the targeted contrast agent in the target area; the storage medium is responsible for storing the computer program corresponding to the ultrasonic imaging method for real-time observing the aggregation of the targeted contrast agent in the target area and the imaging data, for the electronic device to execute the ultrasonic imaging method for real-time observing the aggregation of the targeted contrast agent in the target area.

[0010] The ultrasonic imaging device for real-time observing the aggregation of the targeted contrast agent in the target area includes: a signal acquisition module M1: scanning the target area through a pulse sequence A to acquire the ultrasonic echo signal of the target area. This module suppresses the tissue signal and enhances the contrast agent signal S1 to highlight the echo characteristics of the contrast agent; a signal decomposition module M2: processing the ultrasonic echo signal S1 using a signal decomposition method B to decompose it into an adhesion signal S2 and a random fluctuation signal S3, where S2 is the characteristic signal of the targeted contrast agent and S3 represents the non-targeted microbubble and noise signal; a feature extraction module M3: calculating the temporal variation feature F of the adhesion signal S2 pixel by pixel, and analyzing and extracting the enrichment degree, aggregation rate, and other key quantitative features of the targeted microbubbles; a result output module M4: used to display and output the real-time feature map P based on the signal S2 to achieve high-definition visualization of the microbubble aggregation situation in the target area.

[0011] The ultrasonic imaging system for real-time observing the aggregation of the targeted contrast agent in the target area includes: an acquisition device for executing the first method; the electronic device or the imaging device. Description of the Drawings

[0012] The technical solution of the present disclosure, as well as its further features and advantages, will be best understood from the following detailed description given by way of non-limiting indication with reference to the accompanying drawings, in which:

[0013] Figure 1 is a schematic diagram of an ultrasound imaging method for real-time observation of the aggregation of a targeted contrast agent in a target area provided by an embodiment of the present application.

[0014] Figure 2 is a curve showing the change of the enhanced area of the targeted microbubbles in the target area over time provided by an embodiment of the present application.

[0015] Figure 3 is a schematic diagram of the modules of an ultrasound imaging method for real-time observation of the aggregation of a targeted contrast agent in a target area provided by an embodiment of the present application.

[0016] Figure 4 is a schematic diagram of the structure of an electronic device provided by an embodiment of the present application. Specific implementation

[0017] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present application without creative efforts shall fall within the protection scope of the present application.

[0018] Figure 1 Shown is a schematic diagram of an ultrasound imaging method for real-time observation of the aggregation of a targeted contrast agent in a target area provided by an embodiment of the present application. The method includes the following acquisition and calculation steps:

[0019] Step 110: Scan the target area containing the targeted contrast agent using pulse sequence A and collect the ultrasonic echo signal S1.

[0020] Specifically, for the ultrasonic echo signal S1 of the target area collected, in order to suppress the tissue signal, there are high requirements for pulse sequence A. In this exemplary embodiment, a pulse phase modulation fundamental wave imaging sequence is used to image the target area.

[0021] It should be noted that the targeted contrast agent refers to an acoustic contrast agent modified with a targeting molecule. Exemplary targeting molecules include P-selectin, E-selectin, integrin, fibrin, or VEGFR2 antibody or ligand. In this exemplary embodiment, a VEGFR2 monoclonal antibody is used as the targeting molecule to modify the acoustic contrast agent, and it is injected into the tumor-bearing mice through intravenous injection. The target area is selected as the maximum area of the tumor cross-section.

[0022] Step 120: Decompose the ultrasonic echo signal S1 into an adhesion signal S2 and a random fluctuation signal S3 by using signal decomposition method B.

[0023] In this exemplary embodiment, the singular value decomposition method is adopted to effectively divide the collected signal into two different spaces: a feature space K1 and a feature space K2. In the feature space K1, the adhered signal S2 is identified as the key feature signal representing the targeted contrast agent. Relatively, in the feature space K2, the randomly fluctuating signal S3 mainly corresponds to the noise or the dynamic components of non-target microbubbles.

[0024] Step 130: Quantitatively analyze the temporal variation feature F of the adhesion signal S2 by using algorithm C.

[0025] Specifically, algorithm C is used to plot the feature F of the signal S2 changing with time pixel by pixel in the region of interest, so as to provide a multi-dimensional in-depth analysis of the aggregation of the targeted contrast agent in this region. The implementation manner of algorithm C is flexible and will not be specifically limited here.

[0026] Figure 2 Shown is the curve of the area of the enhanced region of the targeted microbubbles in the target region changing with time provided by an embodiment of the present application.

[0027] From Figure 2 It can be seen that by applying the method of the present application, the enhanced area of the targeted microbubbles in the target region can be quantitatively analyzed at different times, and further, the peak arrival time of the targeted contrast agent can be calculated, thereby providing a more accurate basis for the research on aspects such as the biodistribution and pharmacokinetics of the targeted contrast agent.

[0028] Figure 3 Shown is a schematic module diagram of an ultrasonic molecular imaging method for real-time observing the aggregation of a targeted contrast agent in a target area provided by an embodiment of the present application. It includes:

[0029] (1) A signal acquisition module M1, which is responsible for scanning the target area through a pulse sequence A and acquiring the ultrasonic echo signal S1 of the target area;

[0030] (2) A signal decomposition module M2, which is responsible for decomposing the ultrasonic echo signal S1 into an adhesion signal S2 and a random fluctuation signal S3 by using signal decomposition method B;

[0031] (3) A feature extraction module M3, which is responsible for quantitatively analyzing the temporal variation feature F of the adhesion signal S2 pixel by pixel;

[0032] (4) A result output module M4, which is responsible for displaying and outputting the real-time feature map P of the targeted contrast agent in the target area based on the signal S2.

[0033] Figure 4 Schematic diagram showing the structure of the electronic device 40 provided in an embodiment of the present application. As Figure 4 shown, the electronic device 40 includes one or more processors 410 and a memory 420.

[0034] The processor 410 may be a central processing unit (CPU) or other forms of processing units with data processing capabilities and / or instruction execution capabilities, and may control other components in the electronic device 40 to perform desired functions.

[0035] The memory 420 may include one or more computer program products, and the computer program products may include various forms of computer-readable storage media, such as volatile memory and / or non-volatile memory. Volatile memory may include, for example, random access memory (RAM) and / or high-speed buffer memory (Cache), etc. Non-volatile memory may include, for example, read-only memory (ROM), hard disk, flash memory, etc. One or more computer program instructions may be stored on the computer-readable storage media, and the processor 410 may run the program instructions to implement the ultrasonic imaging method for real-time observation of the aggregation of targeted contrast agents in the target area described above in various embodiments of the present application and / or other desired functions.

[0036] The electronic device 40 may further include: an input device 430 and an output device 440, and these components are interconnected through a bus system and / or other forms of connection mechanisms ( Figure 4 not shown in the figure).

[0037] The input device 430 may include, for example, a keyboard, a mouse, etc.

[0038] The output device 440 may output various information to the outside, and may include, for example, a display, a printer, a speaker, and a communication network and its connected remote output devices, etc.

[0039] Of course, for simplicity, Figure 4 only some of the components related to the present application in the electronic device 40 are shown in the figure, and components such as buses, input / output interfaces, etc. are omitted. In addition, according to specific application scenarios, the electronic device 40 may further include any other appropriate components.

[0040] In addition to the above methods and devices, an embodiment of the present application may also be a computer program product, which includes computer program instructions, and when the computer program instructions are run by a processor, the processor is caused to execute the steps in the ultrasonic imaging method for real-time observation of the aggregation of targeted contrast agents in the target area according to various embodiments of the present application described above in this specification.

[0041] The computer program product may be written in any combination of one or more programming languages for executing the program code of the operations of the embodiments of the present application. The programming languages include object-oriented programming languages such as Java, C++, etc., and also include conventional procedural programming languages such as the "C" language or similar programming languages. The program code may be executed entirely on the user computing device, partially on the user device, executed as a stand-alone software package, partially on the user computing device and partially on a remote computing device, or entirely on a remote computing device or server.

[0042] In addition, an embodiment of the present application may also be a computer-readable storage medium storing computer program instructions, which, when run by a processor, cause the processor to execute the steps in the ultrasonic imaging method for real-time observing the aggregation of a targeted contrast agent in a target area described above in this specification according to various embodiments of the present application. The computer-readable storage medium may employ any combination of one or more readable media. The readable media may be a readable signal medium or a readable storage medium. The readable storage medium may include, for example, but is not limited to, an electrical, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any combination of the above. More specific examples (a non-exhaustive list) of the readable storage medium include: an electrical connection having one or more wires, a portable disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disk read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the above.

[0043] The basic principles of the present application have been described above in conjunction with specific embodiments. However, it should be noted that the advantages, benefits, effects, etc. mentioned in the present application are only examples and not limitations, and it cannot be considered that these advantages, benefits, effects, etc. are essential for each embodiment of the present application. In addition, the above-disclosed specific details are only for illustrative and easy-to-understand purposes and not for limitation. The above details do not limit the present application to necessarily adopt the above specific details for implementation.

[0044] The block diagrams of the devices, apparatuses, equipment, and systems involved in the present application are only illustrative examples and are not intended to require or imply that they must be connected, arranged, and configured in the manner shown in the block diagrams. As those skilled in the art will recognize, these devices, apparatuses, equipment, and systems can be connected, arranged, and configured in any manner. Words such as "including", "comprising", "having", etc. are open-ended terms meaning "including but not limited to" and can be used interchangeably therewith. The word "or" and "and" used herein refer to "and / or" and can be used interchangeably therewith, unless the context clearly indicates otherwise. The word "such as" used herein refers to the phrase "such as but not limited to" and can be used interchangeably therewith.

[0045] The above description is only a description of the preferred embodiments of the present invention and does not limit the scope of the present invention. Without departing from the overall spirit and concept of the present invention, any modifications, equivalent substitutions, and improvements made by those skilled in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. An ultrasound imaging method for real-time observation of the accumulation of targeted contrast agents in a target area, which scans the target area through a specific pulse sequence, separates the targeted contrast agent signal from the non-targeted signal in real time using signal decomposition technology, and finally realizes real-time quantitative visualization of the enrichment degree of targeted microbubbles through pixel-by-pixel temporal characteristic analysis. The specific steps include: (1) For a target area of ​​a contrast agent containing a targeting molecule, an ultrasonic pulse sequence A is applied to scan the target area, wherein an ultrasonic reflection echo signal S1 of the pulse sequence A is a video signal for suppressing background tissue signals; (2) Processing the ultrasonic echo signal S1 by the signal decomposition method B, dividing the signal into two categories: adhesion signal S2 and random fluctuation signal S3, where the adhesion signal S2 is the targeted contrast agent signal and the random fluctuation signal S3 is the interference or noise signal; (3) The time-varying feature F of the S2 signal is extracted pixel by pixel to obtain a quantitative feature map P of the targeted microbubble enrichment degree. Finally, P is used as the ultrasonic molecular imaging result for real-time observation of the accumulation of the targeted contrast agent in the target area.

2. The ultrasound imaging method for real-time observation of the accumulation of a targeted contrast agent in a target area according to claim 1, characterized in that: In step (1), the targeted contrast agent comprises a shell layer modified with a targeting molecule, wherein the targeting molecule is capable of specifically binding to a specific molecule or cell in the target tissue.

3. The ultrasonic imaging method for real-time observation of the accumulation of a targeted contrast agent in a target area according to claim 1, characterized in that: In step (1), the pulse sequence A adopts one of a pulse phase modulation fundamental wave imaging sequence, a pulse phase modulation harmonic imaging sequence, a pulse amplitude modulation fundamental wave imaging sequence, and a pulse amplitude modulation harmonic imaging sequence.

4. The ultrasound imaging method for real-time observation of the accumulation of targeted contrast agents in a target area according to claim 1, characterized in that: In step (2), the signal decomposition method B is used to extract a stable adhesion signal S2 in the slow time direction, which can highlight the dynamic characteristics of the targeted contrast agent and suppress the random fluctuation signal S3; specifically, the decomposition method B adopts a matrix tensor decomposition method, and preferably uses singular value decomposition to classify the signal S1 into two categories, that is, S1 is divided into an adhesion signal S2 and a random fluctuation signal S3.

5. The ultrasonic imaging method for real-time observation of the accumulation of targeted contrast agents in a target area according to claim 1, characterized in that: The feature F is the peak time, maximum growth rate, enhanced region area, enhanced region density, kinetic parameters and other characteristic parameters of the time intensity curve of S2 pixel by pixel. These characteristic parameters are used together to construct a quantitative characteristic map P of the enrichment degree of targeted microbubbles, thereby serving as a basis for real-time observation of the ultrasonic molecular imaging results of the target area aggregation of targeted contrast agents.

6. An ultrasonic imaging system for real-time observation of the accumulation of a targeted contrast agent in a target area, characterized in that: The system provides an electronic device including a processor and a computer storage medium, wherein the processor is used to execute the executable instructions to implement the methods according to claims 1 to 5, and the computer storage medium stores the processor executable instructions.

7. An ultrasonic imaging system for real-time observation of the accumulation of a targeted contrast agent in a target area according to claim 6, characterized in that: The system includes: (1) Signal acquisition module M1, responsible for scanning the target area through pulse sequence A and collecting ultrasonic echo signal S1 of the target area; (2) Signal decomposition module M2, responsible for decomposing the ultrasonic echo signal S1 into adhesion signal S2 and random fluctuation signal S3 through signal decomposition method B; (3) Feature extraction module M3, responsible for extracting the time-varying features F of the adhesion signal S2 pixel by pixel; (4) Result output module M4, responsible for displaying and outputting real-time feature map P.

Images