A method for guiding axillary sentinel lymph node puncture based on skin ultrasound contrast

Abstract

The application relates to the technical field of medical devices, in particular to a skin ultrasound contrast-based axillary sentinel lymph node puncture guiding method. The core of the method is as follows: after injecting an ultrasound contrast agent with a specific particle size through the skin, a preset low-mechanical-index high-frame-rate double-amplitude contrast imaging mode is adopted to dynamically track lymph drainage and sentinel lymph node development, and the enhancement characteristics are recorded; then, under the guidance of multimodal imaging which is fused with real-time contrast, elastic imaging and color Doppler, the target lymph node is accurately punctured and biopsied, and a tissue sample is obtained for pathological analysis. The application realizes integrated operation from sensitive development of the sentinel lymph node, function evaluation to accurate puncture, and provides a non-radiation high-precision puncture guiding method for accurate evaluation of the axillary lymph node state of breast cancer patients before operation.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and more specifically, to a method for guiding axillary sentinel lymph node puncture based on skin ultrasound contrast imaging. Background Technology

[0002] Breast cancer is one of the most common malignant tumors in women. The status of axillary lymph nodes is a key factor in determining clinical stage, treatment plan, and prognosis. Sentinel lymph node biopsy has become the standard minimally invasive method for clinically assessing the status of axillary lymph nodes. Currently, the mainstream techniques at home and abroad rely on the combined tracing of radionuclides and / or blue dyes, and the blue-stained lymph nodes are located and biopsied during the operation using a gamma probe or direct vision. In recent years, ultrasound technology has been explored for preoperative lymph node assessment due to its advantages of being radiation-free, real-time, and convenient. High-frequency ultrasound can show morphological abnormalities of lymph nodes, but its sensitivity to small metastatic lesions within them is limited.

[0003] Despite some progress in existing technologies, significant shortcomings remain. First, in terms of imaging and diagnosis, conventional ultrasound primarily relies on indirect signs such as morphological changes in lymph nodes (e.g., cortical thickening, loss of hilar structure) to assess metastasis, lacking the ability to identify small, normally shaped metastatic lesions. While emerging lymphatic contrast-enhanced ultrasound techniques can visualize lymph nodes through macrophage phagocytosis, the diagnosis of metastasis still depends on indirect imaging features such as "filling defects" or "heterogeneous enhancement," lacking quantitative analysis of lymph node functional status. Second, regarding puncture guidance accuracy, most existing ultrasound contrast-enhanced procedures only achieve surface marking of lymph nodes or guidewire positioning, requiring secondary confirmation with dyes or radionuclides during the procedure. This fails to achieve a one-stop, precise biopsy where "what you see is what you puncture," resulting in a cumbersome process and the risk of positioning errors. Furthermore, some procedures attempt to integrate multiple imaging modalities or contrast agents, such as combining subcutaneous lymphangiography and venography, but this typically requires multiple injections, is complex, and demands sophisticated equipment, increasing the difficulty and cost of implementation and hindering widespread clinical adoption.

[0004] Therefore, this paper proposes a method for axillary sentinel lymph node puncture guidance based on contrast-enhanced ultrasound to address the above-mentioned shortcomings of existing technologies: how to improve the preoperative identification and detection of sentinel lymph nodes, especially small metastatic lesions that are negative on conventional ultrasound; how to achieve integrated and precise guidance of the entire process from lymph node identification to puncture biopsy without radiation, avoiding secondary localization during the operation; and how to reduce the complexity and implementation threshold of the technology while ensuring diagnostic accuracy by optimizing imaging and operation procedures. Summary of the Invention

[0005] In order to overcome the above-mentioned defects of the prior art, embodiments of the present invention provide a method for axillary sentinel lymph node puncture guidance based on skin ultrasound contrast imaging to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging, comprising the following steps:

[0007] S1. Obtain an ultrasound contrast image sequence after intradermal or subcutaneous injection of an ultrasound contrast agent, wherein the injection dose of the ultrasound contrast agent is 0.5 mL to 2.0 mL, and lymphatic drainage is promoted by massage for 1 min to 3 min after injection.

[0008] S2. Process the ultrasound contrast imaging sequence to dynamically record the location, number, and enhancement characteristics of the sentinel lymph nodes. The enhancement characteristics include the uniformity of enhancement of the sentinel lymph nodes in ultrasound contrast imaging mode, the presence of filling defect areas, and the enhancement difference between the cortex and medulla.

[0009] S3. Based on the enhanced features, perform time-intensity curve analysis on the sentinel lymph nodes, calculate the peak intensity, time to peak and peak intensity ratio, and obtain quantitative analysis results;

[0010] S4. Based on the enhancement characteristics and quantitative analysis results, lymph nodes that show overall uneven enhancement, focal areas without enhancement, or eccentric thickening of the cortex with abnormal enhancement are identified as targets with a high probability of metastasis, and puncture guidance information is output.

[0011] Preferably, the ultrasound contrast agent is a microbubble contrast agent that can pass through the interendothelial space of lymphatic vessels and be taken up by macrophages in lymph nodes, with a particle size ranging from 1 μm to 5 μm.

[0012] Preferably, the enhancement features are obtained through dynamic and continuous recording, covering the entire process from the start of contrast agent entry into the sentinel lymph node to the peak enhancement.

[0013] Preferably, the lymph node that first shows up, has the highest imaging intensity, or is directly drained by a lymphatic vessel is defined as the primary sentinel lymph node and is used as the priority target for puncture guidance.

[0014] Preferably, the time-intensity curve analysis specifically includes: setting a region of interest, tracking the change of average signal intensity over time, plotting a time-intensity curve, and calculating the peak intensity, time to peak, and peak intensity ratio.

[0015] Preferably, the puncture guidance information includes: the location coordinates of the target sentinel lymph node, enhanced feature description, quantitative analysis parameters, and the identifier of the priority puncture guidance object.

[0016] Preferably, the ultrasound contrast imaging sequence is acquired under the conditions of a low mechanical index of 0.08 to 0.12, a frame rate of not less than 15 frames per second, and a dual-image display mode.

[0017] Preferably, the time-intensity curve analysis further includes: classifying lymph nodes with a peak intensity ratio below 0.7 as having a high risk of metastasis.

[0018] Preferably, it also includes: acquiring ultrasound elastography data, assessing the stiffness of sentinel lymph nodes, and focusing on areas with abnormally increased stiffness.

[0019] Preferably, it further includes: acquiring color Doppler blood flow imaging data to identify and mark the location of blood vessels around the target lymph node.

[0020] The technical effects and advantages of this invention are as follows:

[0021] Compared to existing technologies, this invention combines preliminary scanning with a low-frequency convex array probe with fine imaging with a high-frequency linear probe. It also presets specific angiography parameters, including low mechanical index, high dynamic range, and high frame rate, and simultaneously activates a real-time dual-panel display mode. The low-frequency probe quickly locates the target area, while the high-frequency probe ensures high imaging resolution for fine lymphatic vessels and lymph node boundaries. The optimized parameter settings maximize the excitation of microbubble harmonic signals while suppressing their destruction. The dual-panel display provides the operator with both pure angiography blood flow information and anatomical background, achieving earlier, clearer, and more stable continuous imaging of sentinel lymph nodes. This effectively extends the diagnostic window available for operation and lays a reliable imaging foundation for subsequent precise puncture.

[0022] Compared to existing technologies, this invention integrates information from three imaging modalities—real-time ultrasound contrast imaging, color Doppler flow imaging, and real-time ultrasound elastography—during the puncture guidance phase. Color Doppler pre-identifies and avoids major blood vessels along the puncture path, reducing the risk of bleeding. Elastography's sensitivity to tissue stiffness identifies sclerotic lesions that may not be clearly visible on traditional imaging. Guided in real-time by dual contrast images, the puncture needle is precisely directed to these structurally and functionally abnormal areas, enabling a comprehensive assessment and targeting of the target lymph node's multidimensional biological characteristics. This elevates puncture biopsy from purely morphological guidance to a dual structural and functional guidance approach, significantly improving the accuracy and representativeness of micrometastases, thereby enhancing diagnostic sensitivity and specificity.

[0023] Compared to existing technologies, this invention utilizes the time-intensity curve analysis software built into ultrasound equipment to quantitatively analyze the dynamic imaging process, obtaining perfusion parameters such as area under the curve, peak intensity, and transit time. This transforms subjective image observation into objective numerical indicators. By quantitatively analyzing the microcirculation perfusion within lymph nodes, it provides objective evidence beyond morphology for assessing their physiological state. This assists operators in more scientifically identifying early metastatic lymph nodes that show no obvious morphological changes but have already exhibited functional abnormalities. It reduces over-reliance on the operator's personal experience, enhances the objectivity and repeatability of metastatic lymph node interpretation, and provides important auxiliary decision-making information for accurate preoperative assessment. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the sentinel lymph node imaging process of the present invention.

[0025] Figure 2 This is a schematic diagram of the multimodal imaging-guided puncture of the present invention.

[0026] Figure 3 This is a schematic diagram of the quantitative analysis and evaluation of the present invention.

[0027] Figure 4 This is a schematic diagram of the integrated operation process of the present invention. Detailed Implementation

[0028] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example

[0029] As attached Figures 1 to 4 The following is a method for guiding axillary sentinel lymph node puncture based on skin ultrasound contrast imaging, and its specific implementation details are as follows:

[0030] Step 1: Preoperative preparation and targeted ultrasound contrast agent injection

[0031] A phospholipid-shell perfluorocarbon gas microbubble contrast agent with a particle size distribution ranging from 1.0 μm to 3.0 μm was selected. This particle size range ensures that the microbubbles cannot directly penetrate the normal capillary endothelium, but can pass through the gaps between lymphatic endothelial cells, thus being specifically captured within the lymphatic vessels. After reconstitution, it was injected into the dermis around the areola under real-time ultrasound two-dimensional imaging monitoring. The dermis is rich in a dense capillary lymphatic network, and this injection site ensures efficient uptake of the contrast agent. Immediately after injection, targeted massage was performed with optimized pressure (50 kPa - 80 kPa) and duration (2 min - 3 min) to simulate physiological tissue fluid flow, actively "pushing" the contrast agent microbubbles into the lymphatic drainage pathway, facilitating clear visualization of the lymphatic vessel chain and sentinel lymph nodes.

[0032] Step 2: Dual-modal real-time ultrasound contrast imaging and parameter co-optimization

[0033] The operator first uses a convex array probe with a frequency of 5 MHz to 8 MHz to perform a wide-area, deep preliminary scan to quickly locate possible lymph node clusters in the axillary region. This "wide-angle scanning" strategy avoids the field of view limitations that may result from directly using a high-frequency linear probe, ensuring that no irregularly located SLNs are missed.

[0034] After initial localization, the system immediately switches to a high-frequency linear probe with a frequency of 8 MHz to 15 MHz for "close-up imaging." At this point, key imaging parameters are collaboratively set:

[0035] Low mechanical index (0.08 - 0.12): Matches the resonant frequency of the contrast agent microbubbles, enabling them to generate strong nonlinear harmonic signals, while greatly reducing the damage of sound pressure to the microbubbles, thus achieving "continuous imaging" of the microbubbles and making dynamic observation for up to several minutes possible.

[0036] High frame rate (≥ 15 fps): ensures that the continuous dynamic process of lymphatic perfusion and lymph node enhancement can be captured, avoiding the omission of transient key perfusion features due to low frame rate.

[0037] Entering the real-time dual-image display mode, the left image, a pure harmonic contrast image, is highly sensitive to microbubble signals due to the filtering out of tissue background, and is specifically used to detect the contrast of lymphatic vessels and SLNs. The right image, a real-time fused image, overlays the contrast signal (pseudocolor) onto a two-dimensional anatomical image, and is specifically used for localization and relationship determination, allowing the operator to clearly see the anatomical relationship between the contrasted SLN and surrounding blood vessels, nerves, and muscles, thereby transforming the "contrast agent-lymphatic flow" formed after injection into a visible and stable image.

[0038] Step 3: SLN status assessment and target selection based on dynamic imagery and quantitative analysis

[0039] The purpose of this step is to select the most suitable targets for puncture biopsy from all visualized lymph nodes. Dynamic observation is maintained throughout the process, from the visualization of lymphatic vessels to the peak enhancement of SLNs and even the beginning of their clearance.

[0040] First, qualitative observation and preliminary screening are performed: the operator directly observes the enhancement pattern of the SLN based on the fused images. A normal SLN typically shows rapid, uniform, and strong overall enhancement, with a clear boundary between the cortex and medulla. A suspicious SLN may show: filling defects (metastatic lesions occupy space, without macrophages phagocytizing microvesicles), heterogeneous cortical thickening with decreased enhancement (tumor cell infiltration replacing normal structures), or delayed perfusion (metastatic lesions destroying or compressing microvessels within the lymph node).

[0041] Quantitative analysis provides objective evidence and reduces subjective misjudgment. It is achieved through time-intensity curve analysis, and the operation steps are as follows:

[0042] Define the region of interest: In the saved dynamic contrast-enhanced video, delineate a region of interest (ROI) of uniform size within the solid area of ​​the target SLN (avoiding potentially large filling defects) and within a nearby, identified normal tissue (such as muscle). The average pixel intensity within this ROI will be automatically tracked by the system.

[0043] Let the area of ​​the ROI of the SLN be... The average signal strength within it at time point t is .

[0044] Let the area of ​​the ROI of the reference tissue be... The average signal strength within it at time point t is .

[0045] The system will automatically generate time-intensity curves and calculate key parameters. , A curve that changes over time.

[0046] Calculate peak intensity: Find the peak intensity of each curve.

[0047] Peak intensity ratio calculation: This parameter normalizes for differences between devices and individuals and reflects the relative blood supply richness of the SLN.

[0048] Calculate the time to peak concentration: from the end of injection. The time point when the intensity reaches its peak The interval.

[0049] Parameter Application and Decision-Making: The calculated PIR and TTP values ​​are used to aid in judgment. Numerous clinical studies have shown that metastatic lymph nodes often exhibit microcirculatory obstruction and abnormal vascular distribution. Therefore, when a lymph node's PIR value is significantly lower than 1.0 (e.g., < 0.7), and / or its TTP value is significantly longer than that of a normal lymph node or reference tissue, the objective evidence for classifying this node as a "high-risk metastatic" node is very strong. This quantitative result corroborates the aforementioned qualitative observations (such as filling defects), jointly guiding operators to prioritize such nodes as puncture targets.

[0050] Step 4: Precise puncture path planning and execution based on multimodal information fusion

[0051] After identifying the target SLN and the suspicious target points within it, the puncture is not performed immediately, but rather a virtual path planning phase is conducted first.

[0052] First, plan a safe path: On a real-time ultrasound 2D grayscale image, pre-determine the puncture point and needle path. Then, activate color Doppler flow imaging (CDFI) to scan the pre-determined needle path and its surroundings. CDFI overlays the blood flow signals within the vessel onto the 2D image in color-coded form. The operator then fine-tunes the puncture point and angle accordingly, ensuring the planned needle path avoids all larger vessels displayed as color signals, thereby minimizing the risk of puncture bleeding.

[0053] After precise target identification and confirmation of the safe path, real-time ultrasound elastography is restarted. Elastography reflects tissue stiffness by applying a small stimulus (mechanical compression or acoustic radiation force) to the tissue and detecting the resulting deformation (strain). Malignant tumor tissue is typically harder and appears as a blue or dark blue area on the elastography image. The operator fuses or displays the elastography image alongside a grayscale image, clearly showing which area within the target SLN exhibits abnormal stiffness. This "hard area" often spatially overlaps with the "filling defect area" or "hypo-enhancing area" indicated by contrast imaging, further confirming it as the most suspicious lesion core area and the final target for biopsy.

[0054] Real-time guided puncture: The operator performs the puncture under the guidance of a real-time dual-panel display mode.

[0055] Simultaneously monitor two images: the fused image on the right ensures clear visibility of the target SLN and target point; the pure contrast image or 2D grayscale image on the left provides the clearest display of the needle tip echo. Once the needle tip confirms it has reached the preset target point on the image, the biopsy gun is triggered. To ensure sample representativeness, 1 to 3 samples are taken from the same target SLN, with a slight retraction and angle adjustment (5° - 10°) after each sample. This aims to obtain tissue from different parts of the lesion area, thereby increasing the probability of capturing micrometastases.

[0056] Step 5: Postoperative immediate assessment and sample standardization

[0057] Postoperative assessment was performed immediately after the puncture. The ultrasound mode was switched back to low-frequency angiography mode for rapid scanning of the punctured SLN. The purpose of this procedure was:

[0058] First, observe the integrity of the lymph node structure;

[0059] Second, confirm that there is no active bleeding (manifested as contrast agent leaking from inside and outside the blood vessels into the interstitial space).

[0060] Meanwhile, the acquired tissue samples are immediately and systematically processed. They are laid flat on filter paper, gently straightened, and then immersed in a sufficient volume of 4% neutral formaldehyde fixative. The volume of the fixative should be at least 10 times the volume of the tissue, and the fixation time should be no less than 6 hours. This standardized procedure is to prevent tissue autolysis, avoid artificial artifacts, and ensure that subsequent paraffin embedding, sectioning, and HE staining yield high-quality pathological sections, thereby guaranteeing the accuracy of the final diagnosis.

[0061] Step 6: Diagnostic Information Integration and Archiving

[0062] Once the procedure is complete, the diverse information generated by this method is systematically integrated, including dynamic contrast imaging (showing the perfusion characteristics of the SLN), elastography (showing tissue stiffness), video recording of the puncture process (proving the accuracy of the biopsy), and the final pathological diagnosis report. This information collectively constitutes a complete and comprehensive preoperative SLN assessment file, providing crucial evidence for clinicians to develop individualized surgical plans and leaving a complete and traceable data chain for academic research and technical review.

[0063] Finally, the following points should be noted: First, in the description of this application, it should be noted that, unless otherwise specified and limited, the terms "installation", "connection", and "linkage" should be interpreted broadly, and can be mechanical or electrical connections, or internal connections between two components, or direct connections. "Up", "down", "left", "right", etc. are only used to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may change.

[0064] Secondly: The accompanying drawings of the embodiments disclosed in this invention only involve the structures involved in the embodiments disclosed in this invention. Other structures can refer to the general design. In the absence of conflict, the same embodiment and different embodiments of this invention can be combined with each other.

[0065] In conclusion, the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for guiding axillary sentinel lymph node puncture based on subcutaneous ultrasound contrast imaging, characterized in that, Includes the following steps: S1. Obtain an ultrasound contrast image sequence after intradermal or subcutaneous injection of an ultrasound contrast agent, wherein the injection dose of the ultrasound contrast agent is 0.5 mL to 2.0 mL, and lymphatic drainage is promoted by massage for 1 min to 3 min after injection. S2. Process the ultrasound contrast imaging sequence to dynamically record the location, number, and enhancement characteristics of the sentinel lymph nodes. The enhancement characteristics include the uniformity of enhancement of the sentinel lymph nodes in ultrasound contrast imaging mode, the presence of filling defect areas, and the enhancement difference between the cortex and medulla. S3. Based on the enhanced features, perform time-intensity curve analysis on the sentinel lymph nodes, calculate the peak intensity, time to peak and peak intensity ratio, and obtain quantitative analysis results; S4. Based on the enhancement characteristics and quantitative analysis results, lymph nodes that show overall uneven enhancement, focal areas without enhancement, or eccentric thickening of the cortex with abnormal enhancement are identified as targets with a high probability of metastasis, and puncture guidance information is output.

2. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, The ultrasound contrast agent is a microbubble contrast agent that can pass through the interendothelial space of lymphatic vessels and be taken up by macrophages in lymph nodes, with a particle size ranging from 1 μm to 5 μm.

3. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, The enhancement features were obtained through dynamic and continuous recording, covering the entire process from the start of contrast agent entry into the sentinel lymph node to the peak enhancement.

4. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, The lymph nodes that first show up, have the highest intensity of contrast, or are directly drained by lymphatic vessels are defined as the primary sentinel lymph nodes and are the priority targets for puncture guidance.

5. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, The time-intensity curve analysis specifically includes: setting a region of interest, tracking the change of average signal intensity over time, plotting a time-intensity curve, and calculating the peak intensity, time to peak, and peak intensity ratio.

6. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, The puncture guidance information includes: the location coordinates of the target sentinel lymph node, enhanced feature description, quantitative analysis parameters, and the identifier of the priority puncture guidance object.

7. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, The ultrasound contrast imaging sequence was acquired under conditions of a low mechanical index of 0.08 to 0.12, a frame rate of not less than 15 frames per second, and a dual-image display mode.

8. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, The time-intensity curve analysis also includes classifying lymph nodes with a peak intensity ratio below 0.7 as having a high risk of metastasis.

9. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, Also includes: Acquire ultrasound elastography data to assess the stiffness of sentinel lymph nodes, and focus on areas with abnormally increased stiffness.

10. The method for axillary sentinel lymph node puncture guidance based on subcutaneous ultrasound contrast imaging according to claim 1, characterized in that, Also includes: Acquire color Doppler blood flow imaging data to identify and mark the location of blood vessels around the target lymph node.

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