Coronary microcirculation disturbance molecular image characterization method based on multi-omics technology and nuclide probe and application of coronary microcirculation disturbance molecular image characterization method

Abstract

The invention discloses a coronary microcirculation disturbance molecular image characterization method based on a multi-omics technology and a nuclide probe and application of the coronary microcirculation disturbance molecular image characterization method, and relates to the technical field of medical diagnosis. The method comprises the following steps: S1, constructing animal models with various pathological characteristics, simulating clinical types of patients suffering from myocardial microvascular diseases, and obtaining heart tissues of the patients after successful modeling; s2, integrating a multi-omics method to screen out key difference features capable of distinguishing each pathological type; s3, labeling the identified key differential molecules by using a radionuclide labeling method, and forming a nuclide probe library of the myocardial microvascular disease in combination with an existing probe; and S4, performing joint analysis on the multi-probe data to construct a joint characterization spectrum: extracting respective image characterization of the multi-probe image data of the same animal to form a multi-probe image characterization spectrum.

Description

Technical Field

[0001] The present invention relates to the field of medical diagnosis technology, and in particular to a molecular imaging characterization method for coronary microcirculation disorders based on multi-omics technology and radionuclide probes and its application. Background Art

[0002] Myocardial microvascular disease is extremely harmful to human health, especially for patients with coronary heart disease, diabetes and hypertension. The disease mainly occurs in the small branches of the coronary arteries, accounting for 95% of the coronary arteries. Structural or functional abnormalities of these microvessels can lead to acute or non-acute myocardial ischemia, increasing health risks. From the perspective of incidence, it is estimated that there are 50 million patients with myocardial microvascular disease. However, due to the lack of obvious symptoms, the misdiagnosis rate is very high, and most of the conditions are not discovered, resulting in poor prognosis. Data show that the risk of adverse cardiac events in patients with myocardial microvascular disease is 5 times higher than that of non-patients. Therefore, accurate diagnosis and targeted intervention are crucial to improving patient prognosis. The causes of myocardial microvascular disease are complex, including multiple pathogenic factors such as coronary heart disease, diabetes, hypertension, obesity and cardiomyopathy. These factors together lead to key pathological links such as endothelial dysfunction, myocardial fibrosis, myocardial inflammation, and abnormal energy metabolism, which in turn lead to serious consequences such as myocardial ischemia, infarction and heart failure.

[0003] Current diagnostic techniques mainly reflect changes in blood flow and are difficult to directly reveal the specific conditions of the pathological links. This limitation makes it impossible for us to achieve accurate diagnosis and treatment of myocardial microvascular disease. Therefore, it is particularly important to explore diagnostic techniques that can visualize key pathological links, especially breakthroughs in nuclear medicine technology. Therefore, we proposed a molecular imaging characterization method for coronary microcirculatory disorders based on multi-omics technology and radionuclide probes and its application to solve the above problems.

[0004] The above information disclosed in this background technology is only used to increase the understanding of the background technology of the present invention and therefore, it may include information that does not constitute the prior art known to ordinary technicians in this field. Summary of the invention

[0005] The purpose of the present invention is to provide a molecular imaging characterization method for coronary microcirculation disorders based on multi-omics technology and radionuclide probes and its application to solve the problems raised by the above background technology.

[0006] To achieve the above object, the present invention provides the following technical solution: a molecular imaging characterization method for coronary microcirculation disorders based on multi-omics technology and radionuclide probes, comprising the following steps:

[0007] S1: Construct animal models with multiple pathological characteristics to simulate the types of patients with clinical myocardial microvascular disease, and obtain their heart tissue after successful modeling;

[0008] S2: Integrate multi-omics approaches to screen out key differential features that can distinguish each pathological type;

[0009] S3: Use radionuclide labeling method to label the key differential molecules identified, and combine with existing probes to form a radionuclide probe library for myocardial microvascular disease;

[0010] S4: Joint analysis of multi-probe data to construct a joint representation spectrum: For multi-probe imaging data of the same animal, extract their respective image representations to form a multi-probe image representation spectrum.

[0011] Preferably, the animal models with multiple pathological characteristics in S1 include high-fat diet feeding, diabetes, hypertension, sodium laurate stimulation, microsphere embolization, and hypertrophic cardiomyopathy animal models, and the animals are mainly rodents.

[0012] Preferably, the multi-omics method in S2 includes genomics, transcriptomics, proteomics and metabolomics.

[0013] Preferably, the probes combined in the S3 include 18F-FDG (sugar metabolism imaging), 18F-FTHA (lipid metabolism imaging), 18F-FAPI (fibrosis imaging), 68Ga-CXCR4 (inflammation imaging), 18F-Flurpiridaz (perfusion imaging / mitochondrial function imaging), and also include key differential features screened by multi-omics methods and probes labeled with radionuclides.

[0014] Preferably, the image representation in S4 includes information on the shape, size, distribution, and functional parameters of the lesion.

[0015] The present invention also provides the application of the above-mentioned molecular imaging characterization method of coronary microcirculation disorder based on multi-omics technology and radionuclide probes in the diagnosis of myocardial microvascular diseases.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The present invention uses a multi-omics approach to screen out the features most relevant to the disease, uses a radionuclide labeling method in combination with existing probes to form a radionuclide probe library for myocardial microvascular disease, and ultimately forms a multi-probe imaging characterization spectrum, providing support for visualizing key pathological links in diagnosis, thereby achieving accurate diagnosis and treatment of myocardial microvascular disease.

[0018] The above summary is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments and features described above, further aspects, embodiments and features of the present invention will be readily apparent by reference to the accompanying drawings and the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 18F-Flurpiridaz imaging for high-fat diet-fed animal models;

[0020] Figure 2 68Ga-CXCR4 imaging in animal models fed a high-fat diet;

[0021] Figure 3 18F-FAPI imaging for animal models fed a high-fat diet;

[0022] Figure 4 18F-FTHA imaging for animal models fed a high-fat diet;

[0023] Figure 5 18F-Flurpiridaz imaging for animal models of microsphere embolization;

[0024] Figure 6 18F-FAPI imaging of animal models of microsphere embolization;

[0025] Figure 7 18F-FDG imaging for the animal model of microsphere embolization. DETAILED DESCRIPTION

[0026] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] A molecular imaging characterization method for coronary microcirculation disorders based on multi-omics technology and radionuclide probes comprises the following steps:

[0028] S1: Construct animal models with multiple pathological characteristics to simulate the types of patients with clinical myocardial microvascular disease, and obtain their heart tissues after successful modeling.

[0029] Animal models with various pathological characteristics include high-fat diet feeding, diabetes, hypertension, sodium laurate stimulation, microsphere embolization, and hypertrophic cardiomyopathy animal models, and the animals are mainly rodents.

[0030] S2: An integrated multi-omics approach screens out key differential features that can distinguish each pathological type.

[0031] Multi-omics approaches include genomics, transcriptomics, proteomics, and metabolomics. For example, genomic analysis may reveal abnormal expression of genes related to angiogenesis (such as VEGF) and endothelial function (such as eNOS); proteomics analysis can confirm the manifestation of these gene changes at the protein level; metabolomics analysis may find changes in glucose metabolism or lipid metabolism, reflecting metabolic reprogramming in myocardial microvascular disease.

[0032] S3: Use radionuclide labeling method to label the key differential molecules identified, and combine with existing probes to form a radionuclide probe library for myocardial microvascular disease.

[0033] The probes include 18F-FDG (glucose metabolism imaging), 18F-FTHA (lipid metabolism imaging), 18F-FAPI (fibrosis imaging), 68Ga-CXCR4 (inflammation imaging), 18F-Flurpiridaz (perfusion imaging / mitochondrial function imaging), as well as key differential features screened out through multi-omics methods and probes labeled with radionuclides.

[0034] S4: Joint analysis of multi-probe data to construct a joint representation spectrum: For multi-probe imaging data of the same animal, extract their respective image representations to form a multi-probe image representation spectrum.

[0035] Image characterization includes information on the shape, size, distribution, and functional parameters of the lesions.

[0036] Case 1

[0037] The animal model fed with a high-fat diet was imaged using 18F-FTHA, 18F-FAPI, 18F-Flurpiridaz, and 68Ga-CXCR4 MicroPET / CT. Figure 1-4 As shown in Figure 2, the direct reflection of multi-nuclide probe imaging shows that the energy metabolism reconstruction of the high-fat diet model (simulating CMVD patients with clinical hyperlipidemia and atherosclerosis) is the main pathological feature and potential optimal therapeutic target during the pathogenic process.

[0038] Case 2

[0039] The animal model of microsphere embolization was imaged using 18F-FDG, 18F-FAPI, and 18F-Flurpiridaz. Figure 5-7 As shown. Through the intuitive reflection of the existing multi-nuclide probe imaging, it can be seen that in the microsphere embolization model (simulating CMVD patients after PCI of clinical acute myocardial infarction), energy metabolism reconstruction is an important pathological feature in the early pathogenic process, while fibrosis is not obvious.

[0040] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example" or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, unless they are contradictory.

[0041] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A molecular imaging method for characterizing coronary microcirculatory disorders based on multi-omics technology and radionuclide probes, characterized in that: The steps include: S1: Construct animal models with multiple pathological characteristics to simulate the types of patients with clinical myocardial microvascular disease, and obtain their heart tissue after successful modeling; S2: Integrate multi-omics approaches to screen out key differential features that can distinguish each pathological type; S3: Use radionuclide labeling method to label the key differential molecules identified, and combine with existing probes to form a radionuclide probe library for myocardial microvascular disease; S4: Joint analysis of multi-probe data to construct a joint representation spectrum: For multi-probe imaging data of the same animal, extract their respective image representations to form a multi-probe image representation spectrum.

2. The method for molecular imaging characterization of coronary microcirculatory disorders based on multi-omics technology and radionuclide probes according to claim 1, characterized in that: The animal models with various pathological characteristics in S1 include high-fat diet feeding, diabetes, hypertension, sodium laurate stimulation, microsphere embolization, and hypertrophic cardiomyopathy animal models, and the animals are mainly rodents.

3. The method for molecular imaging characterization of coronary microcirculatory disorders based on multi-omics technology and radionuclide probes according to claim 1, characterized in that: The multi-omics approach in S2 includes genomics, transcriptomics, proteomics and metabolomics.

4. The method for molecular imaging characterization of coronary microcirculatory disorders based on multi-omics technology and radionuclide probes according to claim 1, characterized in that: The probes combined in the S3 include 18F-FDG (sugar metabolism imaging), 18F-FTHA (lipid metabolism imaging), 18F-FAPI (fibrosis imaging), 68Ga-CXCR4 (inflammation imaging), 18F-Flurpiridaz (perfusion imaging / mitochondrial function imaging), and also include key differential features screened by multi-omics methods and probes labeled with radionuclides.

5. The method for molecular imaging characterization of coronary microcirculatory disorders based on multi-omics technology and radionuclide probes according to claim 1, characterized in that: The image representation in S4 includes the shape, size, distribution, and functional parameter information of the lesion.

6. Application of the molecular imaging characterization method for coronary microcirculation disorders based on multi-omics technology and radionuclide probes as described in any one of claims 1 to 5 in the diagnosis of myocardial microvascular diseases.

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