Real-time monitoring method and device for drug perfusion in solid tumor and storage medium

Abstract

The invention discloses a real-time monitoring method and device for drug perfusion in a solid tumor and a storage medium, and belongs to the technical field of perception and detection methods.The method comprises the steps that initial photoacoustic image data, containing depth information, of the solid tumor are obtained through the photoacoustic microscopic imaging technology; performing deep reconstruction on the initial photoacoustic image data to obtain a multi-layer blood vessel structure image; performing enhancement processing on the multi-layer blood vessel structure image to highlight blood vessel features; constructing a three-dimensional blood vessel network model according to the enhanced multi-layer blood vessel structure image; performing microcirculation simulation acceleration solution on the three-dimensional blood vessel network model by using a multi-grid method; based on a microcirculation simulation result, calculating drug perfusion data in the solid tumor by combining a Poiseuille law and a Darcy model, and taking the data as a real-time monitoring result; according to the invention, hydrodynamic simulation and monitoring of blood flow microcirculation are realized.

Description

Technical Field

[0001] The present invention relates to a real-time monitoring method, device and storage medium for drug perfusion in a solid tumor, belonging to the technical field of perception and detection methods. Background Art

[0002] Tumor treatment is the ultimate challenge that humans are currently in urgent need of overcoming. Medical imaging technology plays a vital role in tumor diagnosis, treatment and research. By providing visual information about the internal structure and function of the human body, it helps doctors conduct early cancer detection, cancer treatment planning, preoperative evaluation, postoperative monitoring and disease tracking. The main treatment methods include:

[0003] Surgical treatment: Surgical treatment involves the removal of tumors or tumor tissues through surgery. This is the oldest and most direct tumor treatment method, suitable for most tumors, especially locally resectable solid tumors (such as breast cancer, lung cancer, gastric cancer, etc.).

[0004] Advantages: strong radical effect; fast treatment speed; wide adaptability.

[0005] Disadvantages: Unable to treat metastatic tumors; surgery is risky; recovery after surgery is slow.

[0006] Radiation therapy: Radiation therapy uses high-energy radiation (such as X-rays, gamma rays, etc.) to kill tumor cells or inhibit their proliferation. Radiation can damage the DNA of cancer cells, causing cell death. Radiation therapy can be applied locally or systemically, and is often used to treat local tumors or in combination with other treatments.

[0007] Advantages: Local treatment is effective; no surgery is required, reducing the risk of trauma and infection; effective for deep treatment.

[0008] Disadvantages: Damage to normal tissues; Multiple treatments are required; Radiotherapy is less effective for metastatic tumors or large tumors. The therapeutic effect is affected by the tumor vascular microenvironment.

[0009] Chemotherapy: Chemotherapy is the use of drugs (chemotherapeutics) to kill cancer cells or stop them from growing. Chemotherapy drugs can be injected intravenously or taken orally into the bloodstream and work throughout the body. They are widely used to treat various types of cancer, especially blood cancers (such as leukemia, lymphoma) and other metastatic tumors.

[0010] Advantages: Chemotherapy can effectively treat systemic tumors, especially tumors with distant metastasis; the therapeutic effect can be increased by combining different chemotherapy drugs.

[0011] Disadvantages: Serious side effects; some patients have drug resistance. The therapeutic effect is affected by tumor perfusion.

[0012] Targeted therapy: Targeted therapy uses specific drugs or molecules to target specific molecular targets on tumor cells, interfering with tumor growth, division or metastasis.

[0013] Advantages: strong specificity; individualized treatment;

[0014] Disadvantages: Not all tumors can find effective targets, and the treatment effect varies depending on the tumor type and individual differences. The treatment effect is also affected by tumor perfusion.

[0015] A common problem in the application of radiotherapy, chemotherapy and targeted therapy in the treatment of solid tumors is that the blood vessels around solid tumor tissues are irregular, disordered and immature. These abnormal blood vessels will lead to uneven blood perfusion in the tumor area, resulting in insufficient oxygen and nutrient supply in some areas, forming low oxygen areas (hypoxic areas) in the tumor. Such a microenvironment will reduce the perfusion of chemotherapy drugs to the center of the tumor, reduce the sensitivity of the tumor to radiotherapy, and enhance the resistance of the tumor to targeted therapy.

[0016] At present, vascular normalization has become a means to improve the tumor microenvironment. By improving the structure and function of tumor blood vessels, they are closer to the state of normal tissue blood vessels. Vascular normalization aims to improve these abnormal vascular structures by injecting certain drugs. However, vascular normalization is usually a temporary process. The blood vessels may return to a more normal state in the short term, but over time, the tumor may re-establish a disordered vascular structure. Different patients and different types of tumors may respond differently to vascular normalization treatment, so individualized treatment is required according to the specific situation of the patient in clinical applications. Although vascular normalization may bring some therapeutic benefits, excessive normalization may cause damage to normal tissues, especially when combined therapy is performed, the degree of vascular normalization needs to be carefully controlled. Therefore, how to accurately regulate the vascular normalization process and avoid excessive or insufficient treatment is still a technical problem.

[0017] Here are some medical imaging methods commonly used to monitor vascular normalization in the solid tumor microenvironment:

[0018] Computed Tomography (CT): CT scanning is an imaging method based on X-ray rotation scanning. The computer reconstructs cross-sectional images of the body through X-ray scanning data from multiple angles.

[0019] Disadvantages: Higher radiation dose, not suitable for frequent examinations; only supports tissue imaging.

[0020] Magnetic Resonance Imaging (MRI): MRI uses strong magnetic fields and radio frequency pulses to excite hydrogen nuclei in the body to produce resonance signals, and then reconstructs images by receiving signals. The differences in water content and hydrogen atom distribution in different tissues lead to different signals and generate images.

[0021] Disadvantages: The examination takes a long time and there are certain contraindications for patients with metal implants in their bodies.

[0022] Ultrasound Imaging (USI): Ultrasound imaging uses the reflected signals of high-frequency sound waves to generate images. Ultrasound waves propagate at different speeds in different tissues, and the difference in the reflected signals forms an image.

[0023] Disadvantages: The operation depends on the operator's experience and skills; it is not suitable for areas with more bones and gas.

[0024] Positron Emission Tomography (PET): PET scans are based on tracers labeled with radioactive isotopes. When the radioactive isotopes decay, they release positrons, which produce gamma rays when they meet electrons in the body. Images are constructed by detecting the location of the gamma rays.

[0025] Disadvantages: Higher radiation dose; lower sensitivity for detecting small lesions.

[0026] Fluorescence Imaging (FLI): FLI is a technology that uses fluorescent substances to emit light signals for visual detection.

[0027] Disadvantages: The background noise is high, and the resolution of fluorescence imaging may not be high enough for complex anatomical structures. In addition, this imaging method relies on exogenous fluorescent probes, some of which may have toxicity or metabolic problems, limiting its clinical use.

[0028] At present, mature imaging technologies such as MRI, USI and FLI do provide strong support for the evaluation and optimization of treatment, but in practical applications, these imaging technologies still face some challenges and limitations. For example, MRI is huge in size and has limited monitoring capabilities for dynamic changes; USI faces the problems of low resolution and severe background noise interference; FLI requires injection of exogenous contrast agents, and the targeting and biocompatibility of imaging probes are also major issues. Therefore, there is still a technical gap in real-time, high-resolution monitoring of the regulatory process of microenvironment vascular normalization in solid tumors in vivo. Summary of the invention

[0029] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a method, device and storage medium for real-time monitoring of drug perfusion in solid tumors. The drug perfusion data in solid tumors is calculated by combining Poiseuille's law and Darcy model as real-time monitoring results, thereby realizing fluid dynamics simulation and monitoring of blood microcirculation.

[0030] To achieve the above object, the present invention is implemented by adopting the following technical solutions:

[0031] In a first aspect, the present invention provides a method for real-time monitoring of drug perfusion in a solid tumor, comprising:

[0032] Using photoacoustic microscopy technology to obtain initial photoacoustic image data containing depth information of solid tumors;

[0033] Performing deep reconstruction on the initial photoacoustic image data to obtain a multi-layer vascular structure image;

[0034] Enhance the multi-layer vascular structure image to highlight the vascular features;

[0035] Construct a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image;

[0036] Use multi-grid method to accelerate the solution of microcirculation simulation of three-dimensional vascular network model;

[0037] Based on the microcirculation simulation results, the drug perfusion data in solid tumors are calculated in combination with Poiseuille's law and Darcy model as real-time monitoring results.

[0038] Furthermore, the enhancing process of the multi-layer vascular structure image to highlight the vascular features specifically includes: applying Frangi filtering based on the Hessian matrix to each layer of the vascular structure image.

[0039] Furthermore, constructing a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image includes:

[0040] Importing the enhanced multi-layer vascular structure image into three-dimensional image processing software;

[0041] Apply a 3D volume median filter to remove noise;

[0042] A clean blood vessel model was generated using a threshold segmentation method;

[0043] Surface information was extracted from the cleaned vascular model, diameter distribution was calculated, and a 3D vascular skeleton was created that represented the topological structure and connectivity of the vascular network.

[0044] Furthermore, the use of a multi-grid method to accelerate the solution of microcirculation simulation on a three-dimensional vascular network model includes:

[0045] S1. constructing a simplified vascular network model based on the three-dimensional vascular skeleton on the coarsest grid layer;

[0046] S2. Preliminarily solving the simplified vascular network model to obtain microcirculation simulation results on the coarse grid layer;

[0047] S3, transferring the microcirculation simulation results on the coarse grid layer to the finer grid layer through the interpolation method;

[0048] S4. On a finer grid layer, further solving is performed based on the transferred microcirculation simulation results and a finer vascular network structure to correct and refine the microcirculation simulation results;

[0049] S5. Repeat steps S3 and S4 until the finest grid layer is reached to obtain the final microcirculation simulation result.

[0050] Furthermore, the microcirculation simulation results are combined with Poiseuille's law and Darcy model to calculate the drug perfusion data in the solid tumor as a real-time monitoring result, specifically including:

[0051] Estimate vascular flow using a model based on Poiseuille's law to predict blood pressure and blood flow distribution outcomes throughout the vascular network;

[0052] Results of predicting fluid transport through porous interstitium using a Darcy-based model;

[0053] Combining the blood pressure and blood flow distribution results with the fluid transport results, the interstitial fluid flow rate, interstitial fluid pressure, and interstitial fluid transport efficiency are calculated as the drug perfusion data in solid tumors;

[0054] The calculated drug perfusion data in the solid tumor is used as the real-time monitoring result.

[0055] Furthermore, in the process of accelerating the solution of microcirculation simulation using the multi-grid method, the three-dimensional vascular skeleton is used as the basic structure of microcirculation simulation to guide the fluid dynamics calculation in the simulation process and ensure that the topological consistency and connectivity of the vascular network are maintained when the microcirculation simulation results are transferred between different grid layers;

[0056] In the process of estimating vascular flow using a model based on Poiseuille's law and predicting blood pressure and blood flow distribution results in the entire vascular network, the three-dimensional vascular skeleton is used to determine the blood flow path and flow distribution.

[0057] In a second aspect, the present invention provides a real-time monitoring device for drug perfusion in solid tumors based on photoacoustic imaging, comprising:

[0058] An image acquisition module, used for acquiring initial photoacoustic image data containing depth information of a solid tumor using a photoacoustic microscopy imaging technique;

[0059] A deep reconstruction module is used to deeply reconstruct the initial photoacoustic image data to obtain a multi-layer vascular structure image;

[0060] An enhancement processing module, used for enhancing the multi-layer vascular structure image to highlight the vascular features;

[0061] A model building module, used to build a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image;

[0062] Microcirculation simulation module, used to accelerate the solution of microcirculation simulation of three-dimensional vascular network model using multi-grid method;

[0063] The real-time monitoring module is used to calculate the drug perfusion data in the solid tumor based on the microcirculation simulation results, combined with Poiseuille's law and Darcy model, as the real-time monitoring results.

[0064] In a third aspect, the present invention provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the steps of any of the aforementioned methods.

[0065] In a fourth aspect, the present invention provides a computer device, comprising:

[0066] Memory, for storing computer programs / instructions;

[0067] A processor is used to execute the computer program / instructions to implement the steps of any of the aforementioned methods.

[0068] In a fifth aspect, the present invention provides a computer program product, comprising a computer program / instruction, which implements the steps of any one of the aforementioned methods when executed by a processor.

[0069] Compared with the prior art, the present invention has the following beneficial effects:

[0070] 1. The present invention provides a real-time monitoring method, device and storage medium for drug perfusion in solid tumors. The method comprises the following steps: deeply reconstructing the initial photoacoustic image data to obtain a multi-layered vascular structure image; enhancing the multi-layered vascular structure image to highlight the vascular characteristics; constructing a three-dimensional vascular network model based on the enhanced multi-layered vascular structure image; using a multi-grid method to accelerate the solution of microcirculation simulation of the three-dimensional vascular network model, combining Poiseuille's law and Darcy model to calculate drug perfusion data in solid tumors as real-time monitoring results, thereby realizing fluid dynamics simulation and monitoring of blood microcirculation.

[0071] 2. The present invention reconstructs the original data from the depth perspective and enhances the image resolution by applying Frangi filtering based on the Hessian matrix. The algorithm has low computational cost and is easy to integrate.

[0072] 3. The present invention uses a multi-grid method to accelerate the blood flow solution process in the complex vascular network in a solid tumor, greatly accelerates the solution convergence speed, reduces the calculation time, and improves the real-time performance of the method.

[0073] 4. The present invention uses Poiseuille's law and Darcy's law as models, utilizes the living vascular volume network obtained by imaging, and combines the laws of spatially heterogeneous vascular cavities and interstitial permeability to achieve fluid dynamics simulation of blood microcirculation. The simulation results are basically consistent with the microcirculation characteristics of solid tumor lesions in existing literature. BRIEF DESCRIPTION OF THE DRAWINGS

[0074] Figure 1 This is a flow chart of a method for real-time monitoring of drug perfusion in a solid tumor provided by an embodiment of the present invention;

[0075] Figure 2 is a schematic diagram of the picture enhancement effect provided by an embodiment of the present invention;

[0076] Figure 3 is a schematic diagram of a picture before enhancement provided by an embodiment of the present invention;

[0077] Figure 4 is a schematic diagram of an enhanced picture provided by an embodiment of the present invention;

[0078] Figure 5 is a schematic diagram of a living three-dimensional vascular network provided by an embodiment of the present invention;

[0079] Figure 6 is a schematic diagram of diameter distribution of a vascular network provided by an embodiment of the present invention;

[0080] Figure 7 is a schematic diagram of interstitial fluid flow rate distribution provided by an embodiment of the present invention;

[0081] Figure 8 is a schematic diagram of interstitial fluid pressure distribution provided by an embodiment of the present invention;

[0082] Fig. 9 is a schematic diagram of drug perfusion efficiency distribution in a solid tumor provided by an embodiment of the present invention;

[0083] Fig.10 This is a simulation monitoring calculation flow chart of drug perfusion in solid tumors provided by an embodiment of the present invention. DETAILED DESCRIPTION

[0084] The present invention will be further described below in conjunction with the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and cannot be used to limit the protection scope of the present invention.

[0085] Example 1: This example introduces a method for real-time monitoring of drug perfusion in solid tumors, comprising:

[0086] Using photoacoustic microscopy technology to obtain initial photoacoustic image data containing depth information of solid tumors;

[0087] Performing deep reconstruction on the initial photoacoustic image data to obtain a multi-layer vascular structure image;

[0088] Enhance the multi-layer vascular structure image to highlight the vascular features;

[0089] Construct a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image;

[0090] Use multi-grid method to accelerate the solution of microcirculation simulation of three-dimensional vascular network model;

[0091] Based on the microcirculation simulation results, the drug perfusion data in solid tumors are calculated in combination with Poiseuille's law and Darcy model as real-time monitoring results.

[0092] like Figure 1 As shown, the real-time monitoring method for drug perfusion in solid tumors provided in this embodiment specifically involves the following steps:

[0093] 1. Solid tumor image processing method based on feature processing

[0094] Photoacoustic microscopy technology uses the photoacoustic focus to scan the sample in two dimensions to obtain initial photoacoustic image data (including depth information), such as Figure 2 As shown. First, the image is reconstructed according to the depth. For example, if the two-dimensional scanning pixels are 2000*1500 and the depth information pixels are 70, 70 vascular structure images with a size of 2000*1500 pixels can be obtained. Secondly, these 70 depth layer images are batch processed by applying Frangi filtering based on the Hessian matrix to enhance the tubular information. The Frangi filter was proposed by Frangi in 1998 to detect blood vessels of different shapes and sizes. Due to its powerful performance and adaptability, this filtering method has become a common method for detecting blood vessels in medical imaging. This method uses the Hessian matrix for multi-scale analysis to enhance tubular features and suppress non-tubular noise. The enhancement effect is shown as follows. Figure 2 As shown, the effect is enhanced by about 1 times. In addition, this method has low computational cost and is easy to integrate into the software host computer, which is also valuable in the development of medical devices.

[0095] 2. Construction of three-dimensional vascular network and extraction of computable information

[0096] After processing the slice images, they were imported into Amira software for segmentation and processing of the vascular network. First, a three-dimensional volume median filter was applied to the image to remove noise caused by small bubbles present in the contact between the imaging sample and water or electromagnetic interference caused by the movement of the motor. To evaluate the effect of the Frangi filter and the volume median filter, we compared the details of the vascular network respectively. Figure 3 , Figure 4 As shown, the Frangi filter enhances the vascular signal and provides more capillary details, while the volume median filter attenuates the background noise.

[0097] Next, the threshold segmentation method is used to separate the vascular signal from the remaining background noise to generate a clean vascular model. After segmenting the vascular network, the surface of the 3D vascular model is extracted and its diameter distribution is calculated, such as Figure 5 , Figure 6 Finally, the skeleton extraction function is used to create a three-dimensional vascular skeleton, which can be further used for hemodynamic simulation calculations.

[0098] 3. Acceleration method for vascular network microcirculation simulation calculation

[0099] This method uses the multigrid method to solve the microcirculation simulation of the vascular network in solid tumors. The multigrid method is an efficient numerical method for solving partial differential equations or linear equations, especially for large-scale and complex computational problems. The core idea is to use grids of different resolutions (multi-level grids) to accelerate the convergence of numerical solutions. The multigrid method combines the solution on the coarse grid with the refined solution on the fine grid, thereby accelerating the solution process at all scales at the same time and significantly reducing the computation time.

[0100] Specifically, the multi-grid method iterates through the following steps:

[0101] Smoothing process: At each grid level, smoothing is first performed using Gauss-Seidel iterations to remove low-frequency errors.

[0102] Residual calculation: On each grid layer, the difference between the original equation and the current approximate solution, i.e. the residual, is calculated.

[0103] Coarse grid solution: Solve on a coarse grid. Coarse grid solution can quickly eliminate low-frequency errors because the coarse grid contains more global information.

[0104] Interpolation: The modified solution obtained from the coarse grid is introduced into the fine grid through the Lagrange interpolation limit operator to improve the solution of the fine grid.

[0105] Smoothing and Iteration: After interpolation, further smoothing and iterations are continued on the fine grid to further refine the solution.

[0106] 4. Simulation monitoring of drug perfusion in solid tumors

[0107] The computational framework for calculating the vascular skeleton is divided into two models. The first model estimates the vascular flow based on Poiseuille's law, estimating boundary data by assuming that the microcirculation within the vascular network is responsible for the hemodynamic changes related to blood flow and vascular shear stress. Based on this model, physiologically plausible blood pressure and blood flow distributions throughout the vascular network are estimated. Moreover, the model can be applied to entire large vascular networks (>2 cm 3 And the number of blood vessels> 10 5 ), predicts the fluid dynamics of the entire vascular network while taking into account the inherent structural heterogeneity at the micron scale. The algorithm estimates the unknown boundary conditions by minimizing the squared deviation associated with the target network wall shear stress and pressure, which are derived from independent information about the hemodynamic properties of a typical vascular network. The solution for hemodynamic changes within the model is calculated an average of n times (greater than 12 times), which is as close to the real solid tumor environment as possible. The second model predicts fluid transport through the porous interstitium based on the Darcy model. Among them, blood vessels are represented by a set of discrete nodes connected in series by segment information, and the interstitial fluid exchange rate of the segment is defined by the vascular blood flow solution. Combining the two models, the interstitial fluid flow rate and interstitial fluid pressure in solid tumors are calculated, such as Figure 7 , Figure 8 Finally, the interstitial fluid transfer efficiency (i.e., perfusion) of the entire vascular network was calculated as follows: Fig. 9 As shown in Figure 2, it provides solutions for medical applications such as solid tumor treatment. The specific calculation process is as follows Fig.10 shown.

[0108] The method provided in this embodiment reconstructs the original data from the depth perspective, and enhances the image resolution by applying Frangi filtering based on the Hessian matrix. The algorithm has low computational cost and is easy to integrate.

[0109] The method provided in this embodiment uses a multi-grid method to accelerate the blood flow solution process in the complex vascular network of solid tumors, greatly accelerates the solution convergence speed, reduces the calculation time, and improves the real-time performance of the method.

[0110] The method provided in this embodiment uses Poiseuille's law and Darcy's law as models, utilizes the living vascular volume network obtained by imaging, and combines the laws of spatially heterogeneous vascular cavities and interstitial permeability to achieve fluid dynamics simulation of blood flow microcirculation. The simulation results are basically consistent with the microcirculation characteristics of solid tumor lesions in existing literature.

[0111] Embodiment 2: This embodiment provides a real-time monitoring device for drug perfusion in solid tumors based on photoacoustic imaging, comprising:

[0112] An image acquisition module, used for acquiring initial photoacoustic image data containing depth information of a solid tumor using a photoacoustic microscopy imaging technique;

[0113] A deep reconstruction module is used to deeply reconstruct the initial photoacoustic image data to obtain a multi-layer vascular structure image;

[0114] An enhancement processing module, used for enhancing the multi-layer vascular structure image to highlight the vascular features;

[0115] A model building module, used to build a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image;

[0116] Microcirculation simulation module, used to accelerate the solution of microcirculation simulation of three-dimensional vascular network model using multi-grid method;

[0117] The real-time monitoring module is used to calculate the drug perfusion data in the solid tumor based on the microcirculation simulation results, combined with Poiseuille's law and Darcy model, as the real-time monitoring results.

[0118] The specific functional implementation of each of the above modules can be found in the relevant contents of the method in Example 1 and will not be elaborated here.

[0119] Embodiment 3, this embodiment provides a computer-readable storage medium, on which a computer program is stored, and when the program is executed by a processor, the steps of any one of the methods described in Embodiment 1 are implemented.

[0120] Embodiment 4: This embodiment provides a computer device, including:

[0121] Memory, for storing computer programs / instructions;

[0122] A processor, configured to execute the computer program / instructions to implement the steps of any one of the methods described in Example 1.

[0123] Embodiment 5: This embodiment provides a computer program product, including a computer program / instruction, which implements the steps of any method described in Embodiment 1 when executed by a processor.

[0124] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

[0125] It should be understood by those skilled in the art that the embodiments of the present disclosure may be provided as methods, systems or computer program products. Therefore, the present disclosure may take the form of a complete hardware embodiment, a complete software embodiment or an embodiment combining software and hardware aspects. Moreover, the present disclosure may take the form of a computer program product implemented on one or more computer-usable storage media (including but not limited to disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0126] The present disclosure is described with reference to flowcharts and / or block diagrams of methods, devices (systems) and computer program products according to embodiments of the present disclosure. It should be understood that each process and / or block in the flowchart and / or block diagram and the combination of processes and / or blocks in the flowchart and / or block diagram can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, a special-purpose computer, an embedded processor or other programmable data processing device to produce a machine, so that the instructions executed by the processor of the computer or other programmable data processing device generate instructions for implementing the processes in the flowchart and / or block diagram. Figure 1 A process or multiple processes and / or boxes Figure 1 A device that provides the functions specified in a block or multiple blocks.

[0127] These computer program instructions may also be stored in a computer-readable memory capable of directing a computer or other programmable data processing device to operate in a specific manner, so that the instructions stored in the computer-readable memory produce an article of manufacture comprising an instruction device, which implements the process Figure 1 A process or multiple processes and / or boxes Figure 1 A function specified in one or more boxes.

[0128] These computer program instructions can also be loaded onto a computer or other programmable data processing device so that a series of operating steps are executed on the computer or other programmable device to produce a computer-implemented process, thereby providing instructions for implementing the process in the computer or other programmable device. Figure 1 A process or multiple processes and / or boxes Figure 1 The steps for the functions specified in one or more boxes.

[0129] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present disclosure rather than to limit its protection scope. Although the present disclosure has been described in detail with reference to the above embodiments, ordinary technicians in the relevant field should understand that after reading the present disclosure, those skilled in the art can still make various changes, modifications or equivalent substitutions to the specific implementation methods of the invention, but these changes, modifications or equivalent substitutions are all within the protection scope of the disclosed claims to be approved.

Claims

1. A method for real-time monitoring of drug perfusion in solid tumors, characterized in that: include: Using photoacoustic microscopy technology to obtain initial photoacoustic image data containing depth information of solid tumors; Performing deep reconstruction on the initial photoacoustic image data to obtain a multi-layer vascular structure image; Enhance the multi-layer vascular structure image to highlight the vascular features; Construct a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image; Use multi-grid method to accelerate the solution of microcirculation simulation of three-dimensional vascular network model; Based on the microcirculation simulation results, the drug perfusion data in solid tumors are calculated in combination with Poiseuille's law and Darcy model as real-time monitoring results.

2. The method for real-time monitoring of drug perfusion in solid tumors according to claim 1, characterized in that: The enhancing process of the multi-layer blood vessel structure image to highlight the blood vessel features specifically includes: applying Frangi filtering based on the Hessian matrix to each layer of the blood vessel structure image.

3. The method for real-time monitoring of drug perfusion in solid tumors according to claim 2, characterized in that: The method of constructing a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image comprises: Importing the enhanced multi-layer vascular structure image into three-dimensional image processing software; Apply a 3D volume median filter to remove noise; A clean blood vessel model was generated using a threshold segmentation method; Surface information was extracted from the cleaned vascular model, diameter distribution was calculated, and a 3D vascular skeleton was created that represented the topological structure and connectivity of the vascular network.

4. The method for real-time monitoring of drug perfusion in solid tumors according to claim 3, characterized in that: The method of using a multi-grid method to accelerate the microcirculation simulation of a three-dimensional vascular network model includes: S1. constructing a simplified vascular network model based on the three-dimensional vascular skeleton on the coarsest grid layer; S2. Preliminarily solving the simplified vascular network model to obtain microcirculation simulation results on the coarse grid layer; S3, transferring the microcirculation simulation results on the coarse grid layer to the finer grid layer through the interpolation method; S4. On a finer grid layer, further solving is performed based on the transferred microcirculation simulation results and a finer vascular network structure to correct and refine the microcirculation simulation results; S5. Repeat steps S3 and S4 until the finest grid layer is reached to obtain the final microcirculation simulation result.

5. The method for real-time monitoring of drug perfusion in solid tumors according to claim 4, characterized in that: The microcirculation simulation results are combined with Poiseuille's law and Darcy model to calculate the drug perfusion data in the solid tumor as a real-time monitoring result, specifically including: Estimate vascular flow using a model based on Poiseuille's law to predict blood pressure and blood flow distribution outcomes throughout the vascular network; Results of predicting fluid transport through porous interstitium using a Darcy-based model; Combining the blood pressure and blood flow distribution results with the fluid transport results, the interstitial fluid flow rate, interstitial fluid pressure, and interstitial fluid transport efficiency are calculated as the drug perfusion data in solid tumors; The calculated drug perfusion data in the solid tumor is used as the real-time monitoring result.

6. The method for real-time monitoring of drug perfusion in solid tumors according to claim 5, characterized in that: In the process of accelerating the solution of microcirculation simulation using the multi-grid method, the three-dimensional vascular skeleton is used as the basic structure of microcirculation simulation to guide the fluid dynamics calculation in the simulation process and ensure that the topological consistency and connectivity of the vascular network are maintained when the microcirculation simulation results are transferred between different grid layers; In the process of estimating vascular flow using a model based on Poiseuille's law and predicting blood pressure and blood flow distribution results in the entire vascular network, the three-dimensional vascular skeleton is used to determine the blood flow path and flow distribution.

7. A real-time monitoring device for drug perfusion in solid tumors based on photoacoustic imaging, characterized in that: include: An image acquisition module, used for acquiring initial photoacoustic image data containing depth information of a solid tumor using a photoacoustic microscopy imaging technique; A deep reconstruction module is used to deeply reconstruct the initial photoacoustic image data to obtain a multi-layer vascular structure image; An enhancement processing module, used for enhancing the multi-layer vascular structure image to highlight the vascular features; A model building module, used to build a three-dimensional vascular network model based on the enhanced multi-layer vascular structure image; Microcirculation simulation module, used to accelerate the solution of microcirculation simulation of three-dimensional vascular network model using multi-grid method; The real-time monitoring module is used to calculate the drug perfusion data in the solid tumor based on the microcirculation simulation results, combined with Poiseuille's law and Darcy model, as the real-time monitoring results.

8. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the program is executed by a processor, the steps of the method described in any one of claims 1 to 6 are implemented.

9. A computer device, characterized in that: include: Memory, for storing computer programs / instructions; A processor, configured to execute the computer program / instructions to implement the steps of the method according to any one of claims 1 to 6.

10. A computer program product comprising a computer program / instructions, characterized in that When the computer program / instructions are executed by a processor, the steps of the method according to any one of claims 1 to 6 are implemented.

Images