Evaluation method for treating myocardial microvascular disease by using mesenchymal stem cell exosome based on nuclear medicine imaging technology

Abstract

The invention discloses a nuclear medicine imaging technology-based evaluation method for treating myocardial microvascular diseases by using mesenchymal stem cell exosomes, and relates to the technical field of cardiovascular disease diagnosis. The method comprises the following steps that 1, after a microsphere embolism method is used for modeling, 18F-Flurridaz microPET / CT is used for conducting resting state imaging and Regadenoson load state imaging, Pmod software is used for analysis to obtain myocardial coronary artery blood flow reserve (CFR) of a model mouse, and the myocardial microvessel blood perfusion injury degree is determined; 2, after sequential treatment is carried out through exosomes of the mesenchymal stem cells, a 18F-FDG tracer agent is regularly injected in an intravenous mode, microPET / CT scanning is carried out, and metabolism imaging data of the cardiac muscle of the model mouse is obtained; 3, after scanning, PMOD software is used for processing imaging data, a myocardial bullseye map is generated, the myocardial bullseye map can display metabolism conditions of all segments of the myocardium, and by comparing metabolism values before and after treatment, the metabolism improvement effect of treatment on all the segments of the myocardium is analyzed, and the influence of treatment on myocardial energy metabolism recovery is revealed.

Description

Technical Field

[0001] The present invention relates to the technical field of cardiovascular disease diagnosis, and specifically to an evaluation method for treating myocardial microvascular disease with bone marrow mesenchymal stem cell exosomes based on nuclear medicine imaging technology. Background Art

[0002] Acute myocardial infarction (AMI) is one of the main causes of cardiac function damage. Although percutaneous coronary intervention (PCI) can effectively restore coronary blood flow and improve myocardial blood supply, many patients still face the problem of myocardial microvascular disease (CMD) after acute treatment. CMD is a disease that affects myocardial microvessels (such as arterioles, venules, and capillaries), manifested as microvascular dysfunction, leading to myocardial cell ischemia and imbalanced oxygen supply, and ultimately causing metabolic disorders. Although cardiac angiography can effectively evaluate large vessel stenosis, it is still difficult to detect microvascular function. Existing diagnostic methods are difficult to accurately reveal the degree of microvascular damage, resulting in missed diagnosis or delayed diagnosis of CMD.

[0003] Studies have shown that the occurrence of myocardial microvascular disease is not only manifested as reduced microvascular blood flow, but also accompanied by an imbalance in myocardial energy metabolism. Microvascular disease causes myocardial cells to be unable to obtain sufficient oxygen and glucose, which in turn leads to metabolic disorders. This metabolic imbalance exacerbates the oxidative stress of myocardial cells, leading to the accumulation of metabolites, and ultimately aggravating the functional decline of myocardial tissue. Therefore, it is crucial to restore microvascular function and reestablish energy metabolism balance.

[0004] In recent years, bone marrow mesenchymal stem cells (BMSCs) have become an important direction in the research of cardiovascular disease treatment due to their excellent repair potential. As secretions of stem cells, BMSCs exosomes carry a variety of biologically active molecules (such as RNA, proteins, lipids, etc.), which can regulate signal transmission between cells, improve myocardial microvascular function, reduce inflammatory response and promote the repair of myocardial cells. At the same time, exosomes have good biocompatibility, stability and targeting, can cross biological barriers, and improve myocardial function and metabolic state. Therefore, the use of BMSCs exosomes to treat myocardial microvascular disease may not only provide a new treatment for restoring microvascular function, but also provide a new idea for improving the metabolic disorder of myocardial cells.

[0005] However, there is currently no perfect method that can dynamically and quantitatively evaluate myocardial microvascular disease (CMD) before and after treatment. Therefore, we proposed an evaluation method for bone marrow mesenchymal stem cell exosomes in the treatment of myocardial microvascular disease based on nuclear medicine imaging technology to solve the above problems.

[0006] 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

[0007] The purpose of the present invention is to provide an evaluation method for bone marrow mesenchymal stem cell exosomes in the treatment of myocardial microvascular disease based on nuclear medicine imaging technology to solve the problems raised by the above background technology.

[0008] To achieve the above object, the present invention provides the following technical solution: a method for evaluating bone marrow mesenchymal stem cell exosomes for treating myocardial microvascular disease based on nuclear medical imaging technology, comprising the following steps:

[0009] Step 1: After modeling using the microsphere embolization method, 18F-Flurpiridaz microPET / CT was used to perform resting state and Reganosine stress state imaging, and the myocardial coronary blood flow reserve (CFR) of the model mice was obtained using Pmod software to determine the degree of myocardial microvascular blood perfusion injury;

[0010] Step 2: After sequential treatment with exosomes from bone marrow mesenchymal stem cells, 18F-FDG tracer was injected intravenously regularly and microPET / CT scans were performed to obtain metabolic imaging data of the myocardium of the model mice;

[0011] Step 3: After scanning, use PMOD software to process the imaging data and generate a myocardial bull's eye map, which can display the metabolic status of each myocardial segment. By comparing the metabolic values ​​before and after treatment, the metabolic improvement effect of the treatment on each myocardial segment is analyzed to reveal the impact of the treatment on the recovery of myocardial energy metabolism.

[0012] Compared with the prior art, the present invention has the following beneficial effects:

[0013] The present invention firstly uses 18F-Flurpiridaz microPET / CT imaging to evaluate the degree of damage to blood perfusion in microvessels in myocardial microvascular disease, and then uses 18F-FDG microPET / CT technology to perform dynamic quantitative metabolic evaluation of the damaged myocardium of myocardial microvascular disease before and after treatment. Through this method, the recovery of myocardial microvascular function and the improvement of local metabolic balance can be quantitatively analyzed, providing important imaging basis for evaluating the treatment effect.

[0014] 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

[0015] Figure 1 Schematic diagram of using 18F-Flurpiridaz microPET / CT to assess coronary blood flow reserve in a myocardial microvascular disease model;

[0016] Figure 2 Schematic diagram of using 18F-FDG microPET / CT to monitor metabolic levels in each myocardial segment;

[0017] Figure 3 Schematic diagram of an animal model that simulates myocardial microvascular disease associated with AMI patients undergoing PCI in clinical practice. DETAILED DESCRIPTION

[0018] 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.

[0019] The evaluation method of bone marrow mesenchymal stem cell exosomes for the treatment of myocardial microvascular disease based on nuclear medicine imaging technology includes the following steps:

[0020] Step 1: After modeling using the microsphere embolization method, 18F-Flurpiridaz microPET / CT was used to perform resting state and Reganosine stress state imaging, and the myocardial coronary blood flow reserve (CFR) of the model mice was obtained using Pmod software to determine the degree of myocardial microvascular blood perfusion injury;

[0021] Step 2: After sequential treatment with exosomes from bone marrow mesenchymal stem cells, 18F-FDG tracer was regularly injected intravenously and microPET / CT scans were performed to obtain metabolic imaging data of the myocardium of the model mice;

[0022] Step 3: After scanning, use PMOD software to process the imaging data and generate a myocardial bull's eye map, which can display the metabolic status of each myocardial segment. By comparing the metabolic values ​​before and after treatment, the metabolic improvement effect of the treatment on each myocardial segment is analyzed to reveal the impact of the treatment on the recovery of myocardial energy metabolism.

[0023] Example 1

[0024] 1. Animal model simulating myocardial microvascular disease associated with PCI in patients with AMI

[0025] In order to better understand the mechanism of the occurrence and development of myocardial microvascular dysfunction in patients with AMI after PCI, it is particularly important to establish a suitable animal model. Microsphere embolization is one of the commonly used methods to simulate myocardial microvascular disease. By injecting micron-sized particles into the rat heart, the damage of coronary microvessels is simulated, thereby reproducing the common myocardial microvascular dysfunction in patients with AMI after PCI.

[0026] 2.18F-Flurpiridaz microPET / CT combined with Reganosine stress assessment of myocardial microvascular disease model

[0027] As an emerging detection method, 18F-Flurpiridaz resting and stress state detection can accurately evaluate the coronary microvascular blood flow reserve, and then confirm the presence and severity of microvascular disease. Therefore, in order to fully reflect the multiple pathological characteristics of myocardial microvascular disease after AMI PCI, the combination of microsphere embolization method and Flurpiridaz detection aims to provide a more accurate and comprehensive animal model of myocardial microvascular disease, and provide an effective model basis for subsequent treatment exploration.

[0028] The 18F-Flurpiridaz static PET scanning technology combined with Regadenoson loading drug was used to evaluate the myocardial blood perfusion in the rat myocardial microvascular disease model. The experiment was carried out over two days. On the first day, an 18F-Flurpiridaz microPET / CT scan was performed at rest to record the basal blood flow of the myocardium. On the second day, Regadenoson (loading drug) was injected intravenously 10 seconds in advance to promote myocardial load and increase coronary blood flow. Subsequently, 18F-Flurpiridaz was injected intravenously for 18F-Flurpiridaz microPET / CT imaging under loading state. In this way, the myocardial load response can be effectively induced and its blood flow changes can be monitored. The imaging data was processed by PMOD software to calculate the coronary artery flow. This parameter is used to evaluate changes in myocardial perfusion and further determine whether the myocardial microvascular disease model was successfully established. The schematic diagram of successful modeling is shown in the figure. Figure 3 By comparing the CFR values ​​at rest and under load, the degree of damage to microvascular function and the scope of lesions can be clearly determined.

[0029] 3. Combination of in situ injection of exosomes and tail vein injection for the treatment of myocardial microvascular disease

[0030] Exosome therapy is used, combined with in situ injection and tail vein injection sequential treatment to improve the treatment effect and ensure that exosomes can effectively target damaged myocardial tissue. First, exosomes extracted from bone marrow mesenchymal stem cells are directly injected into the damaged area of ​​myocardial microvascular disease through in situ injection to achieve efficient local treatment. This method enables exosomes to play a stronger repair role in damaged tissues, promote cell repair and regeneration, and improve local microvascular function. Subsequently, the exosomes are further guided to the whole body through tail vein injection to enhance the systemic treatment effect. Tail vein injection ensures that exosomes reach various parts of the body through blood circulation, especially the myocardial area, further promoting myocardial repair and restoration of metabolic balance. The treatment strategy combining the two injection methods can not only achieve local and systemic joint repair, but also enhance the therapeutic effect of exosomes, improve the microvascular function of myocardial microvascular disease and the metabolic state of damaged heart.

[0031] 4.18F-FDG microPET / CT Dynamic Assessment of Myocardial Segmental Metabolism in Myocardial Microvascular Disease

[0032] The 18F-FDG microPET / CT technology was used to conduct dynamic metabolic evaluation of the rat model of myocardial microangiopathy. After treatment, 18F-FDG tracers were regularly injected intravenously and microPET / CT scans were performed to obtain metabolic imaging data of the rat myocardium. After scanning, the imaging data was processed using PMOD software to generate a myocardial bull's eye map, which can display the metabolic status of each segment of the myocardium. By comparing the metabolic values ​​at different stages before and after treatment, the metabolic improvement effect of the treatment on each segment of the myocardium was dynamically analyzed, revealing the effect of the treatment on the recovery of myocardial energy metabolism.

[0033] Metabolic levels of each myocardial segment Figure 2 The evaluation method of the present invention can quantitatively analyze the therapeutic effect, especially the recovery of myocardial microvascular function and the improvement of local metabolic balance, providing an important imaging basis for evaluating the therapeutic effect.

[0034] 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.

[0035] 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 method for evaluating bone marrow mesenchymal stem cell exosomes for the treatment of myocardial microangiopathy based on nuclear medicine imaging technology, characterized in that: The steps include: Step 1: After modeling using the microsphere embolization method, 18F-Flurpiridaz microPET / CT was used to perform resting state and Reganosine stress state imaging, and the myocardial coronary blood flow reserve (CFR) of the model mice was obtained using Pmod software to determine the degree of myocardial microvascular blood perfusion injury; Step 2: After sequential treatment with exosomes from bone marrow mesenchymal stem cells, 18F-FDG tracer was injected intravenously regularly and microPET / CT scans were performed to obtain metabolic imaging data of the myocardium of the model mice; Step 3: After scanning, use PMOD software to process the imaging data and generate a myocardial bull's eye map, which can display the metabolic status of each myocardial segment. By comparing the metabolic values ​​before and after treatment, the metabolic improvement effect of the treatment on each myocardial segment is analyzed to reveal the impact of the treatment on the recovery of myocardial energy metabolism.

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