A method and system for early tumor identification by synergistic effect of temperature-sensitive hydrogel and ultrasound

Abstract

The present application relates to the technical field of tumor medical image diagnosis, and discloses a tumor early identification method and system cooperating with temperature-sensitive hydrogel and ultrasound, comprising a double-network temperature-sensitive contrast agent preparation module, a constant-temperature injection administration module, an in-situ temperature-sensitive phase transition triggering module and a high-frequency ultrasound imaging identification module; the method comprises the following steps: S1, a contrast agent preparation stage; S2, a constant-temperature administration stage; S3, a temperature-sensitive phase transition triggering stage; and S4, an ultrasound identification stage; the present application realizes switch-type ultrasound imaging effect, effectively suppresses the background echo signal of normal tissues, significantly improves the ultrasound echo intensity of a lesion area, greatly improves the imaging signal-to-noise ratio, can clearly distinguish early small tumor lesions from surrounding normal tissues, reduces the interference of background noise on the diagnosis result, and improves the accuracy of tumor early identification.

Description

Technical Field

[0001] This invention relates to the field of tumor medical imaging diagnostic technology, and in particular to a method and system for early tumor identification using thermosensitive hydrogel combined with ultrasound. Background Technology

[0002] Early diagnosis of tumors is a key element in improving the effectiveness of tumor treatment and improving the survival prognosis of patients. Imaging examinations are currently the main means of clinical tumor screening and diagnosis. Ultrasound examination is widely used for screening and follow-up of various solid tumors due to its advantages such as simple operation, no ionizing radiation, and real-time dynamic imaging. Ultrasound contrast imaging technology can further improve image contrast and lesion identification by introducing contrast agents to increase the difference in acoustic impedance between tissues. As the clinical demand for early diagnosis of small tumors continues to increase, the limitations of existing ultrasound contrast agents are gradually becoming apparent, making it difficult to fully meet the application requirements for high-precision early tumor diagnosis. Summary of the Invention

[0003] The purpose of this invention is to provide a method and system for early tumor identification using thermosensitive hydrogel combined with ultrasound, in order to solve the problems mentioned in the background art.

[0004] To achieve the above objectives, the present invention adopts the following technical solution: A thermosensitive hydrogel-assisted ultrasound early tumor identification system includes a dual-network thermosensitive contrast agent preparation module, a constant-temperature injection drug delivery module, an in-situ thermosensitive phase transition triggering module, and a high-frequency ultrasound imaging identification module.

[0005] As a further improvement to this technical solution: the dual-network thermosensitive contrast agent preparation module includes a PVA / PNIPAM dual-network thermosensitive hydrogel system, a perfluoropentane microbubble loading system, a targeted peptide modification system, a water bath heating device, a magnetic stirring device, and a low-temperature freezing device.

[0006] As a further improvement to this technical solution: the PVA / PNIPAM dual-network thermosensitive hydrogel system uses polyvinyl alcohol and N-isopropylacrylamide as the base raw materials, with a mass ratio of 1:1 to 1:3. First, polyvinyl alcohol is dissolved in deionized water and heated to 90 to 95 degrees Celsius to complete the dissolution. After cooling to room temperature, N-isopropylacrylamide monomer is added and stirred evenly. Then, N,N'-methylenebisacrylamide, accounting for 1% to 2% of the mass of N-isopropylacrylamide, is added as a crosslinking agent. Ammonium persulfate and tetramethylethylenediamine are then added to initiate free radical polymerization, forming a preliminary chemical crosslinking network. Subsequently, the product is frozen at -20 degrees Celsius and then thawed at room temperature. This freeze-thaw cycle is repeated 3 to 5 times to construct a physical crosslinking network based on the hydrogen bonding of polyvinyl alcohol segments, ultimately forming a physicochemical dual-network interpenetrating polymer network hydrogel. Its minimum critical dissolution temperature is controlled in the range of 32 to 34 degrees Celsius.

[0007] As a further improvement to this technical solution: In the swelling stage before or after hydrogel polymerization, the perfluoropentane microbubble loading system is mixed with a medical perfluoropentane microbubble suspension at a volume ratio of 5% to 20% into the prepolymer or swelling solution. Through gentle stirring or ultrasonic dispersion, the microbubbles are uniformly distributed in the three-dimensional network structure of the hydrogel, physically retained by the network structure and maintaining structural integrity. The targeted peptide modification system is modified by acryloyl group modification, which couples the N-terminus or side chain of the tumor-targeting peptide to the side chain of polyisopropylacrylamide. The targeted peptide is introduced into the acryloyl group by reacting with hydroxyethyl acrylate, and participates in the reaction as a comonomer during the polymerization process, or is grafted onto the amino group of polyisopropylacrylamide through Michael addition reaction.

[0008] As a further improvement to this technical solution: the in-situ thermosensitive phase change triggering module relies on human physiological temperature and tumor tissue metabolic heat to complete the triggering. When the ambient temperature is higher than the minimum critical dissolution temperature of the hydrogel, the polyisopropylacrylamide chain segments undergo hydrophobic collapse, the overall volume of the hydrogel shrinks, and the microbubbles trapped inside are squeezed, which increases the degree of microbubble deformation and changes the acoustic impedance difference between the microbubbles and the gel matrix.

[0009] As a further improvement to this technical solution: the isothermal injection drug delivery module includes a low-temperature isothermal preservation device and a medical injection device. The low-temperature isothermal preservation device maintains the ambient temperature before the contrast agent is injected, and the medical injection device performs the local delivery of contrast agent around the tumor.

[0010] As a further improvement to this technical solution: the high-frequency ultrasound imaging recognition module includes a high-frequency ultrasound imaging device, a high-frequency ultrasound probe, and an echo signal comparison and recognition logic. The high-frequency ultrasound probe operates in the frequency range of 10 to 15 MHz. The echo signal comparison and recognition logic quantitatively compares the echo intensity values ​​of different regions to locate and identify small tumor lesions.

[0011] A method for early tumor identification using thermosensitive hydrogel combined with ultrasound, comprising the following steps: S1. In the contrast agent preparation stage, a PVA / PNIPAM dual-network thermosensitive hydrogel was prepared, loaded with perfluoropentane microbubbles and modified with targeted peptides to obtain a thermosensitive composite contrast agent. S2, the isothermal drug delivery stage, the thermosensitive composite contrast agent is kept at a constant temperature of 25 to 30 degrees Celsius and delivered to the tumor and surrounding tissue space by local injection around the tumor. S3, the thermosensitive phase transition triggering stage, relies on the physiological temperature of the human body and the metabolic heat of tumor tissue to make the local temperature exceed the minimum critical dissolution temperature of the hydrogel, triggering the hydrogel volume shrinkage and squeezing the internal microbubbles. S4. In the ultrasound identification stage, a 10 to 15 MHz high-frequency ultrasound probe is used to scan the target area, acquire ultrasound echo images, and compare the echo intensity of different areas to locate the tumor lesion.

[0012] Compared with the prior art, the beneficial effects of the present invention are: 1. This invention achieves a switchable ultrasound imaging effect, effectively suppressing background echo signals of normal tissues while significantly increasing the ultrasound echo intensity of the lesion area, greatly improving the imaging signal-to-noise ratio, clearly distinguishing early micro-tumor lesions from surrounding normal tissues, reducing the interference of background noise on diagnostic results, and improving the accuracy of early tumor identification.

[0013] 2. The three-dimensional network structure of the hydrogel of this invention can form a stable coating on the internal microbubbles, prolonging the circulation and retention time of the contrast agent in the body. Combined with surface targeted modification, it can further improve the enrichment efficiency of the contrast agent in tumor tissue. At the same time, the heating process that triggers the imaging can generate a simultaneous thermotherapy effect, which has both diagnostic and therapeutic application value and has the potential for integrated diagnosis and treatment.

[0014] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it according to the contents of the specification, the preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings. Specific embodiments of the present invention are given in detail below with reference to the accompanying drawings. Attached Figure Description

[0015] The accompanying drawings, which are included to provide a further understanding of the invention and form part of this application, illustrate exemplary embodiments of the invention and, together with their description, serve to explain the invention and do not constitute an undue limitation thereof. In the drawings: Figure 1 This is a schematic diagram of a method and system for early tumor identification using thermosensitive hydrogel combined with ultrasound. Detailed Implementation

[0016] The principles and features of the present invention are described below with reference to the accompanying drawings. The examples given are for illustrative purposes only and are not intended to limit the scope of the invention. The invention is described more specifically in the following paragraphs by way of example with reference to the accompanying drawings. It should be noted that the drawings are in a very simplified form and use non-precise proportions, and are only used to facilitate and clarify the illustration of the embodiments of the present invention.

[0017] Please see Figure 1 In this embodiment of the invention, a thermosensitive hydrogel-assisted ultrasound early tumor identification system includes a dual-network thermosensitive contrast agent preparation module, a constant temperature injection drug delivery module, an in-situ thermosensitive phase transition triggering module, and a high-frequency ultrasound imaging identification module. Specifically, the system includes a dual-network thermosensitive contrast agent preparation module, a constant temperature injection drug delivery module, an in-situ thermosensitive phase transition triggering module, and a high-frequency ultrasound imaging recognition module; The dual-network thermosensitive contrast agent preparation module completes the entire process of preparing thermosensitive composite contrast agents; the isothermal injection drug delivery module completes the in vivo delivery of contrast agents under set temperature conditions; the in-situ thermosensitive phase transition triggering module triggers the hydrogel to undergo a volume phase transition, changing the acoustic impedance characteristics of the microbubbles; and the high-frequency ultrasound imaging and recognition module acquires ultrasound signals and completes the localization and recognition of tumor lesions.

[0018] The dual-network thermosensitive contrast agent preparation module includes a PVA / PNIPAM dual-network thermosensitive hydrogel system, a perfluoropentane microbubble loading system, a targeted peptide modification system, a water bath heating device, a magnetic stirring device, and a low-temperature freezing device. Specifically, the module includes a PVA / PNIPAM dual-network thermosensitive hydrogel system, a perfluoropentane microbubble loading system, a targeted peptide modification system, a water bath heating device, a magnetic stirring device, and a low-temperature freezing device; The PVA / PNIPAM dual-network thermosensitive hydrogel system serves as the main matrix for the contrast agent, exhibiting temperature-responsive phase transition characteristics. The perfluoropentane microbubble loading system supports perfluoropentane microbubbles, distributing them within the three-dimensional network of the hydrogel. The targeted peptide modification system links tumor-targeting peptides to the hydrogel side chains. A water bath heating device provides the heating environment required for raw material dissolution. A magnetic stirring device provides the stirring power for raw material mixing and reaction processes. A low-temperature freezing device provides the low-temperature environment required for the hydrogel freeze-thaw process.

[0019] The PVA / PNIPAM dual-network thermosensitive hydrogel system uses polyvinyl alcohol and N-isopropylacrylamide as the base raw materials, with a mass ratio of 1:1 to 1:3. First, polyvinyl alcohol is dissolved in deionized water and heated to 90 to 95 degrees Celsius to complete the dissolution. After cooling to room temperature, N-isopropylacrylamide monomer is added and stirred evenly. Then, N,N'-methylenebisacrylamide, accounting for 1% to 2% of the mass of N-isopropylacrylamide, is added as a crosslinking agent. Ammonium persulfate and tetramethylethylenediamine are then added to initiate free radical polymerization, forming a preliminary chemical crosslinking network. Subsequently, the product is frozen at -20 degrees Celsius and then thawed at room temperature. This freeze-thaw cycle is repeated 3 to 5 times to build a physical crosslinking network based on the hydrogen bonding of polyvinyl alcohol segments, ultimately forming a physicochemical dual-network interpenetrating polymer network hydrogel. Its minimum critical dissolution temperature is controlled in the range of 32 to 34 degrees Celsius. Specifically, polyvinyl alcohol (PVA) forms the main body of the hydrogel's physical cross-linking network, creating physical cross-linking points through hydrogen bonding. N-isopropylacrylamide (NPA) is the core monomer responsible for the hydrogel's temperature-sensitive properties; the polymerized molecular chains exhibit temperature-responsive conformational changes. The mass ratio of NPA to NPA is set to 1:1 to 1:3. N,N'-methylenebisacrylamide (NMP) is used as a chemical cross-linking agent, constructing a chemical cross-linking network through covalent bonds, and its addition amount is 1% to 2% of the mass of NMP. Ammonium persulfate is used as a free radical polymerization initiator, and tetramethylethylenediamine (TME) is used as a polymerization accelerator. Both of these agents jointly initiate the free radical polymerization reaction of the monomers, forming a preliminary chemical cross-linking network. The freeze-thaw cycle alternates between freezing at -20°C and thawing at room temperature, with 3 to 5 cycles, inducing the formation of hydrogen-bonded physical cross-linking points in the PVA segments. Ultimately, a physicochemically interpenetrating polymer network hydrogel is formed, with its minimum critical dissolution temperature controlled within the range of 32 to 34°C.

[0020] In the swelling stage before or after hydrogel polymerization, the perfluoropentane microbubble loading system mixes a medical perfluoropentane microbubble suspension into the prepolymer or swelling solution at a volume ratio of 5% to 20%. Through gentle stirring or ultrasonic dispersion, the microbubbles are uniformly distributed in the three-dimensional network structure of the hydrogel, physically retained by the network structure and maintaining structural integrity. The targeted peptide modification system uses acryloyl group modification to couple the N-terminus or side chain of the tumor-targeting peptide to the side chain of polyisopropylacrylamide. The targeted peptide is introduced into the acryloyl group by reacting with hydroxyethyl acrylate, and participates in the reaction as a comonomer during the polymerization process, or is grafted onto the amino group of polyisopropylacrylamide through Michael addition reaction. Specifically, medical perfluoropentane microbubbles are ultrasonic scattering media that can vaporize to form microbubble structures at body temperature. The microbubble addition process is carried out before or after the swelling stage of hydrogel polymerization. The medical perfluoropentane microbubble suspension is mixed into the prepolymer or swelling solution at a volume ratio of 5% to 20%. Gentle stirring or ultrasonic dispersion is used to ensure that the microbubbles are evenly distributed in the gel system and physically retained by the three-dimensional network of the gel, thus maintaining the integrity of the structure. Tumor-targeting peptides are polypeptide molecules with the ability to specifically bind to tumor tissues. Acryloyl group modification is used to couple the N-terminus or side chain of the tumor-targeting peptide to the side chain of polyisopropylacrylamide. Specifically, the targeting peptide is introduced into the acryloyl group by reacting it with hydroxyethyl acrylate, and then participates in the reaction as a comonomer during the polymerization process, or it is grafted onto the amino group of polyisopropylacrylamide through Michael addition reaction.

[0021] The in-situ thermosensitive phase transition triggering module relies on human physiological temperature and tumor tissue metabolic heat to complete the triggering. When the ambient temperature is higher than the minimum critical dissolution temperature of the hydrogel, the polyisopropylacrylamide chain segments undergo hydrophobic collapse, the overall volume of the hydrogel shrinks, and the trapped microbubbles are squeezed, which increases the degree of microbubble deformation and changes the acoustic impedance difference between the microbubbles and the gel matrix. Specifically, the triggering sources are human physiological temperature and metabolic heat of tumor tissue; when the ambient temperature is higher than the minimum critical dissolution temperature of the hydrogel, the polyisopropylacrylamide segments undergo hydrophobic collapse, the overall volume of the hydrogel shrinks, and it exerts a squeezing effect on the trapped microbubbles, which increases the degree of microbubble deformation and changes the acoustic impedance difference between the microbubbles and the gel matrix.

[0022] The isothermal injection drug delivery module includes a cryogenic isothermal preservation device and a medical injection device. The cryogenic isothermal preservation device maintains the ambient temperature before contrast agent injection, and the medical injection device performs the local delivery of contrast agent around the tumor. Specifically, the cryogenic preservation device maintains the ambient temperature before contrast agent injection; the medical injection device performs the local delivery of contrast agent around the tumor.

[0023] The high-frequency ultrasound imaging recognition module includes a high-frequency ultrasound imaging device, a high-frequency ultrasound probe, and echo signal comparison and recognition logic. The high-frequency ultrasound probe operates in the frequency range of 10 to 15 MHz. The echo signal comparison and recognition logic quantitatively compares the echo intensity values ​​of different regions to locate and identify small tumor lesions. Specifically, the module includes a high-frequency ultrasound imaging device, a high-frequency ultrasound probe, and echo signal comparison and recognition logic; High-frequency ultrasound imaging equipment emits ultrasound waves and receives echo signals to generate ultrasound images; the high-frequency ultrasound probe is the transmitter and receiver of ultrasound waves, with a working frequency range of 10 to 15 MHz; the echo signal comparison and identification logic quantitatively compares the echo intensity values ​​of different regions to locate and identify small tumor lesions.

[0024] A method for early tumor identification using thermosensitive hydrogel combined with ultrasound, comprising the following steps: S1. In the contrast agent preparation stage, a PVA / PNIPAM dual-network thermosensitive hydrogel was prepared, loaded with perfluoropentane microbubbles and modified with targeted peptides to obtain a thermosensitive composite contrast agent. S2, the isothermal drug delivery stage, the thermosensitive composite contrast agent is kept at a constant temperature of 25 to 30 degrees Celsius and delivered to the tumor and surrounding tissue space by local injection around the tumor. S3, the thermosensitive phase transition triggering stage, relies on the physiological temperature of the human body and the metabolic heat of tumor tissue to make the local temperature exceed the minimum critical dissolution temperature of the hydrogel, triggering the hydrogel volume shrinkage and squeezing the internal microbubbles. S4. Ultrasound identification stage: A 10 to 15 MHz high-frequency ultrasound probe is used to scan the target area, acquire ultrasound echo images, and compare the echo intensity of different areas to locate the tumor lesion. Specifically, in the S1 contrast agent preparation stage, a PVA / PNIPAM dual-network thermosensitive hydrogel is prepared, loaded with perfluoropentane microbubbles and modified with targeted peptides to obtain a thermosensitive composite contrast agent. S2, the isothermal drug delivery stage, the thermosensitive composite contrast agent is kept at a constant temperature of 25 to 30 degrees Celsius and delivered to the tumor and surrounding tissue space by local injection around the tumor. S3, the thermosensitive phase transition triggering stage, relies on the physiological temperature of the human body and the metabolic heat of tumor tissue to make the local temperature exceed the minimum critical dissolution temperature of the hydrogel, triggering the hydrogel volume shrinkage and squeezing the internal microbubbles. S4. In the ultrasound identification stage, a 10 to 15 MHz high-frequency ultrasound probe is used to scan the target area, acquire ultrasound echo images, and compare the echo intensity of different areas to locate the tumor lesion.

[0025] The method of use and working principle of this invention are as follows: Instructions for use: Store the thermosensitive composite contrast agent at a suitable temperature and deliver it to the tumor and surrounding tissues via peritumoral injection. After the contrast agent has been fully distributed in the tissue and completed its thermosensitive phase transition, use a high-frequency ultrasound imaging device to scan the target area. By comparing the difference in echo intensity between the tumor area and normal tissue, early identification of tumor lesions can be achieved.

[0026] Working principle: Utilizing the temperature-responsive phase transition properties of thermosensitive hydrogels, on / off ultrasound imaging is achieved. At room temperature, the hydrogel is in a swollen state, with the internally loaded microbubbles gently encapsulated by a three-dimensional network. At this time, the acoustic impedance difference between the gel system and the surrounding tissue is small, and there is no obvious echo signal under ultrasound. When the ambient temperature rises above the phase transition threshold, the hydrogel molecular chains undergo hydrophobic collapse accompanied by volume shrinkage, which compresses the trapped microbubbles, increasing the degree of microbubble deformation and significantly enhancing the acoustic impedance difference between the microbubbles and the gel matrix. Under ultrasound irradiation, a strong backscattering signal is generated. Combined with the tumor region enrichment effect brought about by targeted modification, the echo intensity of the tumor site is significantly higher than that of normal tissue, thereby achieving specific imaging and identification of tumor lesions.

[0027] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any way. Those skilled in the art can readily implement the present invention based on the description and drawings above. However, any modifications, alterations, and variations made by those skilled in the art without departing from the scope of the present invention using the disclosed technical content are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, and variations made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the present invention.

Claims

1. A thermosensitive hydrogel-assisted ultrasound-based early tumor identification system, characterized in that, It includes a dual-network thermosensitive contrast agent preparation module, a constant temperature injection drug delivery module, an in-situ thermosensitive phase transition triggering module, and a high-frequency ultrasound imaging recognition module.

2. The thermosensitive hydrogel-assisted ultrasound early tumor identification system according to claim 1, characterized in that, The dual-network thermosensitive contrast agent preparation module includes a PVA / PNIPAM dual-network thermosensitive hydrogel system, a perfluoropentane microbubble loading system, a targeted peptide modification system, a water bath heating device, a magnetic stirring device, and a low-temperature freezing device.

3. The thermosensitive hydrogel-assisted ultrasound early tumor identification system according to claim 2, characterized in that, The PVA / PNIPAM dual-network thermosensitive hydrogel system uses polyvinyl alcohol and N-isopropylacrylamide as the base raw materials, with a mass ratio of 1:1 to 1:

3. First, polyvinyl alcohol is dissolved in deionized water and heated to 90 to 95 degrees Celsius to complete the dissolution. After cooling to room temperature, N-isopropylacrylamide monomer is added and stirred evenly. Then, N,N'-methylenebisacrylamide, accounting for 1% to 2% of the mass of N-isopropylacrylamide, is added as a crosslinking agent. Ammonium persulfate and tetramethylethylenediamine are then added to initiate free radical polymerization, forming a preliminary chemical crosslinking network. Subsequently, the product is frozen at -20 degrees Celsius and then thawed at room temperature. This freeze-thaw cycle is repeated 3 to 5 times to construct a physical crosslinking network based on the hydrogen bonding of polyvinyl alcohol segments, ultimately forming a physicochemical dual-network interpenetrating polymer network hydrogel. Its minimum critical dissolution temperature is controlled in the range of 32 to 34 degrees Celsius.

4. The thermosensitive hydrogel-assisted ultrasound early tumor identification system according to claim 2, characterized in that, In the swelling stage before or after hydrogel polymerization, the perfluoropentane microbubble loading system involves mixing a medical perfluoropentane microbubble suspension into the prepolymer or swelling solution at a volume ratio of 5% to 20%. Through gentle stirring or ultrasonic dispersion, the microbubbles are uniformly distributed in the three-dimensional network structure of the hydrogel, physically retained by the network structure and maintaining structural integrity. The targeted peptide modification system uses acryloyl group modification to couple the N-terminus or side chain of the tumor-targeting peptide to the side chain of polyisopropylacrylamide. The targeted peptide is introduced into the acryloyl group by reacting with hydroxyethyl acrylate, participating in the reaction as a comonomer during polymerization, or grafted onto the amino group of polyisopropylacrylamide through Michael addition reaction.

5. The thermosensitive hydrogel-assisted ultrasound early tumor identification system according to claim 1, characterized in that, The in-situ thermosensitive phase transition triggering module relies on human physiological temperature and tumor tissue metabolic heat to complete the triggering. When the ambient temperature is higher than the minimum critical dissolution temperature of the hydrogel, the polyisopropylacrylamide chain segments undergo hydrophobic collapse, the overall volume of the hydrogel shrinks, and the trapped microbubbles are squeezed, which increases the degree of microbubble deformation and changes the acoustic impedance difference between the microbubbles and the gel matrix.

6. The thermosensitive hydrogel-assisted ultrasound early tumor identification system according to claim 1, characterized in that, The isothermal injection drug delivery module includes a low-temperature isothermal preservation device and a medical injection device. The low-temperature isothermal preservation device maintains the ambient temperature before contrast agent injection, and the medical injection device performs local contrast agent delivery to the peritumoral area.

7. The thermosensitive hydrogel-assisted ultrasound early tumor identification system according to claim 1, characterized in that, The high-frequency ultrasound imaging recognition module includes a high-frequency ultrasound imaging device, a high-frequency ultrasound probe, and an echo signal comparison and recognition logic. The high-frequency ultrasound probe operates in the frequency range of 10 to 15 MHz. The echo signal comparison and recognition logic quantitatively compares the echo intensity values ​​of different regions to locate and identify small tumor lesions.

8. A method for early tumor identification using thermosensitive hydrogel combined with ultrasound, applied to the early tumor identification system using thermosensitive hydrogel combined with ultrasound as described in any one of claims 1-7, characterized in that, Includes the following steps: S1. In the contrast agent preparation stage, a PVA / PNIPAM dual-network thermosensitive hydrogel was prepared, loaded with perfluoropentane microbubbles and modified with targeted peptides to obtain a thermosensitive composite contrast agent. S2, the isothermal drug delivery stage, the thermosensitive composite contrast agent is kept at a constant temperature of 25 to 30 degrees Celsius and delivered to the tumor and surrounding tissue space by local injection around the tumor. S3, the thermosensitive phase transition triggering stage, relies on the physiological temperature of the human body and the metabolic heat of tumor tissue to make the local temperature exceed the minimum critical dissolution temperature of the hydrogel, triggering the hydrogel volume shrinkage and squeezing the internal microbubbles. S4. In the ultrasound identification stage, a 10 to 15 MHz high-frequency ultrasound probe is used to scan the target area, acquire ultrasound echo images, and compare the echo intensity of different areas to locate the tumor lesion.

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