In-vivo and in-vitro modeling method for myocardial infarction ischemic injury

Abstract

The invention relates to the technical field of image analysis of injury models, in particular to an in-vivo and in-vitro modeling method for myocardial infarction ischemic injury, which comprises the following steps of: determining an injury dilation prediction sequence of each myocardial sub-region by pre-constructing a blood supply association relationship between each myocardial sub-region and each blood supply artery; the method comprises the following steps: determining whether a myocardial infarction and ischemic injury sample model is qualified or not by acquiring the confidence coefficient of each myocardial infarction region contour section, pre-regulating and controlling the injury of the ischemic injury, redefining the myocardial infarction region contour section with the suspected confidence coefficient, and judging whether the myocardial infarction and ischemic injury sample model is qualified or not according to the difference quantity of injury characterization quantities in a continuous injury identification period. According to the method, a GDF-15 research test is carried out on a qualified myocardial infarction ischemic injury sample model, so that the injury expansion of an infarction area is predicted in the continuous batch construction process of the myocardial infarction ischemic injury model, the model construction process is regulated and controlled in a targeted manner, and the uniformity and effectiveness of continuous construction of the model are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of image analysis of injury models, and in particular to an in vivo and in vitro modeling method of myocardial infarction ischemic injury. Background Art

[0002] Myocardial infarction is one of the leading causes of death and disease worldwide. Its pathogenesis is due to coronary artery obstruction, which causes long-term insufficient blood supply to the myocardial tissue, thereby triggering myocardial ischemic necrosis. Even with significant progress in reperfusion therapy, the morbidity and mortality of myocardial infarction remain high. Current methods for constructing ischemic injury models of myocardial infarction, such as ligating the supplying arteries or storing the myocardium under hypoxic conditions, can simulate the pathological process of myocardial infarction to a certain extent, but have many shortcomings. Traditional modeling methods cannot accurately control the development and distribution of infarct area, and are prone to uneven expansion of infarct area in different regions. This makes the modeling uniformity and stability poor, and cannot accurately reflect the actual development of myocardial infarction in different myocardial sub-regions. In addition, the existing model construction process lacks sufficient consideration of the relationship between the blood supply of each myocardial sub-region and the supplying artery, and fails to effectively utilize clinical data such as coronary angiography grade to optimize the modeling process, resulting in a certain deviation between the model and the actual clinical situation.

[0003] For example, Chinese Patent Publication No.: CN110197713A, the invention discloses a medical image processing method, device, equipment and medium, and the medical image processing method disclosed in the application includes: acquiring a first image; the first image is any image frame in a serial cardiogram; obtaining a region of interest in the first image and a first position of a myocardial spot in the region of interest through a segmentation model; determining the second position of the corresponding myocardial spot in the second image according to the first position of the myocardial spot; the second image is the Nth image frame adjacent to the first image in the serial cardiogram; extracting a first feature image of the first position in the first image, and a second feature image of the second position in the second image; determining the motion trajectory of the myocardial spot through the first feature image and the second feature image.

[0004] The following problems also exist in the prior art:

[0005] Existing technologies cannot solve the problems of inaccurate definition of the infarct area outline and unpredictable damage expansion in the continuous batch construction process of myocardial infarction ischemic injury models, resulting in a lack of targeted process control of model construction, affecting the uniformity and effectiveness of continuous model construction. Summary of the Invention

[0006] To this end, the present invention provides a method for in vivo and in vitro modeling of ischemic injury in myocardial infarction, so as to overcome the problem in the prior art that in the continuous and batch construction of the ischemic injury model in myocardial infarction, the delineation of the infarct area contour is inaccurate and the injury expansion is difficult to predict, resulting in the lack of pertinence in the process control of model construction.

[0007] To achieve the above object, the present invention provides a method for in vivo and in vitro modeling of ischemic injury in myocardial infarction, including:

[0008] Ligating the blood supply artery of a mouse to construct an in vivo model of a myocardial ischemic injury sample, and storing the myocardium of the mouse under hypoxic conditions to construct an in vitro model of a myocardial ischemic injury sample;

[0009] Pre-constructing the blood supply correlation between each myocardial sub-region and each blood supply artery, and determining the injury expansion prediction order of each myocardial sub-region according to the coronary angiography grading of each myocardial sub-region;

[0010] Performing pre-regulation of injury creation on each myocardial sub-region, including regulating the blood flow reserve of the blood supply artery associated with each myocardial sub-region, or regulating the supply amount of antioxidants in each myocardial sub-region;

[0011] Screening injury regulation sub-regions based on the injury expansion prediction order, and obtaining the myocardial infarct area contour of each injury regulation sub-region according to the medical image of each injury regulation sub-region after completing the pre-regulation of injury creation;

[0012] Determining a number of contour representation unit vectors according to the myocardial infarct area contour, determining the confidence level of each myocardial infarct area contour segment according to the direction change of the contour representation unit vector within a preset injury identification period, and re-sampling the myocardial infarct area contour segment with doubtful confidence level to obtain a re-defined myocardial infarct area contour segment;

[0013] Determining the difference amount of the injury representation quantity of each injury regulation sub-region within consecutive injury identification periods based on the myocardial infarct area contour of each injury regulation sub-region, and determining whether the myocardial infarction ischemic injury sample model is qualified based on the difference amount;

[0014] Conducting a GDF-15 research test on the determined qualified myocardial infarction ischemic injury sample model.

[0015] Further, the process of determining the injury expansion prediction order of each myocardial sub-region includes:

[0016] Pre-obtaining the coronary angiography grading of each myocardial sub-region, and sorting each myocardial sub-region in ascending order according to the coronary angiography grading;

[0017] Determine the sorting order of each myocardial sub-region as the prediction order of injury expansion for each myocardial sub-region.

[0018] Further, the process of selecting pre-regulation of injury creation for ischemic injury includes:

[0019] If the current myocardial infarction ischemic injury model is an in-vivo modeling method, select the reserve amount of regulating blood flow reserve for the blood supply arteries associated with each myocardial sub-region;

[0020] If the current myocardial infarction ischemic injury model is an in-vitro modeling method, select the supply amount of regulating antioxidants for each myocardial sub-region.

[0021] Further, determine the reserve amount of blood flow reserve for the blood supply arteries associated with each myocardial sub-region and the supply amount of regulating antioxidants for each myocardial sub-region according to the injury expansion prediction order;

[0022] Among them, the reserve amount of the blood flow reserve decreases sequentially according to the injury expansion prediction order, and the supply amount of the antioxidant decreases sequentially according to the injury expansion prediction order.

[0023] Further, the process of screening injury regulation sub-regions includes:

[0024] Determine the myocardial sub-regions corresponding to the first and last positions in the injury expansion prediction order according to the injury expansion prediction order of each myocardial sub-region;

[0025] Respectively screen the myocardial sub-regions corresponding to the first order and the last order as injury regulation sub-regions;

[0026] Among them, screen the myocardial sub-region corresponding to the first order as the first characteristic sub-region of injury regulation, and screen the myocardial sub-region corresponding to the last order as the second characteristic sub-region of injury regulation.

[0027] Further, the process of obtaining the myocardial infarction region contour of each injury regulation sub-region includes:

[0028] Obtain the medical images of the first characteristic sub-region of injury regulation and the second characteristic sub-region of injury regulation, and remove noise and correct the image gray level of the medical images;

[0029] Use image segmentation algorithms and edge detection algorithms to determine the first myocardial infarction region contour within the first characteristic sub-region of injury regulation and the second myocardial infarction region contour within the second characteristic sub-region of injury regulation.

[0030] Further, determining the contour representation unit vector includes:

[0031] Respectively determine the centroid of the contour of the first myocardial infarction region corresponding to the start moment of the injury identification period and the centroid of the contour of the second myocardial infarction region corresponding to the start moment of the injury identification period;

[0032] Respectively construct the contour representation unit vectors of the first myocardial infarction region contour and the second myocardial infarction region contour;

[0033] Among them, the contour representation unit vector of the first myocardial infarction region contour takes the centroid of the contour of the first myocardial infarction region as the starting point of the vector, and respectively takes a number of marked points set on the contour of the first myocardial infarction region as the ending points of the vector. The contour representation unit vector of the second myocardial infarction region contour takes the centroid of the contour of the second myocardial infarction region as the starting point of the vector, and respectively takes a number of marked points set on the contour of the second myocardial infarction region as the ending points of the vector.

[0034] Furthermore, the process of determining the confidence of each myocardial infarction region contour segment includes:

[0035] Taking the ending point of the contour representation unit vector as the benchmark, determine the myocardial infarction region contour segment with a preset length on the myocardial infarction region contour;

[0036] Determine the vector angles of each contour representation unit vector at the start moment and the end moment of the injury identification period;

[0037] Determine the reciprocal of the vector angle as the confidence of the myocardial infarction region contour segment corresponding to the contour representation unit vector.

[0038] Furthermore, the process of determining the myocardial infarction region contour segment with doubtful confidence and obtaining the redefined myocardial infarction region contour segment includes:

[0039] If the confidence of the myocardial infarction region contour segment does not meet the contour construction confidence requirement, it is determined that the confidence of the myocardial infarction region contour segment is doubtful;

[0040] Resample the myocardial infarction region contour segment with doubtful confidence, fit the contour of the resampled myocardial infarction region contour segment with the myocardial infarction region contour segment with doubtful confidence, and obtain the redefined myocardial infarction region contour segment;

[0041] Among them, the contour construction confidence requirement is that the confidence is lower than the preset confidence threshold.

[0042] Furthermore, the process of determining whether the myocardial infarction ischemic injury sample model is qualified includes:

[0043] Determining the myocardial infarction region contours of each damage control sub-region at the start and end of the damage identification cycle, and determining the area change of the myocardial infarction region contours within the damage identification cycle based on the pixel area;

[0044] Calculating the difference in the change in the contour area of the myocardial infarction region between adjacent injury identification cycles, and determining the average of the plurality of differences as the difference;

[0045] Based on the comparison result of the difference comparison value and the preset identification error reference value, it is determined whether the myocardial infarction ischemic injury sample model is qualified;

[0046] Among them, if the difference comparison value exceeds the identification error reference value, the current myocardial infarction ischemic damage model is judged to be unqualified; if the difference comparison value does not exceed the identification error reference value, the current myocardial infarction ischemic damage model is judged to be qualified, and the difference comparison value is the difference between the difference of the first myocardial infarction area contour and the difference of the second myocardial infarction area contour.

[0047] Compared with the prior art, the beneficial effect of the present invention lies in that the present invention pre-constructs the blood supply correlation relationship between each myocardial sub-region and each blood supply artery, determines the damage expansion prediction order of each myocardial sub-region, pre-regulates the ischemic damage of each myocardial sub-region, obtains the myocardial infarction area contour of each damage regulation sub-region through the medical image of the screened damage regulation sub-region, determines the confidence of each myocardial infarction area contour segment according to the direction change of the contour characterization unit vector of the myocardial infarction area contour, and redefines the myocardial infarction area contour segment with questionable confidence, determines the difference in damage characterization quantity within the continuous damage identification cycle through the myocardial infarction area contour of each damage regulation sub-region, so as to determine whether the myocardial infarction ischemic damage sample model is qualified, and further, realizes the prediction of damage expansion of the infarction area in the process of continuous batch construction of myocardial infarction ischemic damage model, and regulates the model construction process in a targeted manner to improve the uniformity and effectiveness of the continuous construction of the model.

[0048] Furthermore, by determining a predicted order of lesion expansion, the present invention can clarify the order of the speed of infarct expansion in different myocardial subregions, thereby providing a reasonable basis for subsequent pre-regulation of ischemic injury in each myocardial subregion and facilitating targeted regulation according to the characteristics of different regions. It can be understood that the degree of stenosis and blockage of the coronary artery corresponding to each myocardial subregion can be graded through coronary angiography grading, with a higher grade indicating a relatively milder stenosis or blockage of the coronary artery. Based on the above-mentioned relationship between coronary angiography grading and the speed of infarct expansion in myocardial subregions, the myocardial subregions are sorted in order of coronary angiography grading from small to large. In fact, the myocardial subregions are arranged in order of their infarct expansion from fast to slow. The order and relative speed of lesion expansion in each myocardial subregion throughout the entire myocardial infarction ischemic injury process are clearly determined, facilitating subsequent targeted research, analysis, and regulation based on the lesion expansion characteristics of different myocardial subregions, thereby achieving the prediction of lesion expansion in the infarct region during the continuous batch construction of myocardial infarction ischemic injury models.

[0049] Furthermore, under the in vivo modeling method of the present invention, the blood flow reserve of the blood supply artery associated with each myocardial sub-region is selected to be regulated. It can be understood that the blood flow reserve is regulated according to the order of damage expansion prediction because different myocardial sub-regions have different sensitivities to ischemia and damage expansion rates due to their different coronary angiography grades. The myocardial sub-regions with a higher order of damage expansion prediction are more susceptible to damage and expand faster under ischemic conditions, and are given relatively more blood flow reserves, while the regulation amount is reduced for the areas with slow infarct expansion. In this way, the myocardium of different regions can be evenly injured during the ischemic injury process; similarly, the supply of antioxidants is reduced in sequence according to the order of damage expansion prediction because the myocardial sub-regions with a higher order of damage expansion prediction have a relatively faster damage expansion rate and require more antioxidants to slow down the damage rate. In this way, the myocardium of different regions can be evenly injured during the ischemic injury process, thereby achieving targeted regulation of the model construction process.

[0050] Furthermore, the present invention selects the first and last two myocardial sub-regions corresponding to the order of damage expansion prediction as damage regulation sub-regions, which can accurately locate the areas with the fastest and slowest infarct expansion. By comparing and analyzing these two characteristic sub-regions with obvious differences, we can better understand the pathophysiological mechanism of myocardial infarction at different stages and different expansion speeds, and realize targeted regulation of the model construction process.

[0051] Furthermore, the present invention determines the centroid of the myocardial infarction region contour at the start moment of the injury identification cycle, and taking this as the starting point, sets marker points on the contour to construct contour representation unit vectors, transforming the complex geometric shape of the myocardial infarction region contour into a set of quantifiable vector data. By constructing vectors based on the contour centroid, it can simultaneously reflect the overall shape and local details of the myocardial infarction region contour. The contour centroid represents the geometric center of the contour. The vectors from the centroid to each marker point not only reflect the relative positional relationship between each part of the contour and the whole, but also can reflect the deformation of the local contour through the change of the vectors, which helps to comprehensively grasp the development and change of the myocardial infarction region. By setting a confidence threshold to determine whether the confidence of the contour segment is doubtful, and resampling and contour fitting for the contour segments with confidence lower than the threshold, it can effectively correct the possibly inaccurate contour definition, achieving targeted regulation of the model construction process.

[0052] Furthermore, the present invention determines a contour segment of a preset length based on the end point of the contour representation unit vector, and determines the confidence by calculating the reciprocal of the angle between the vectors at the start and end moments of the injury identification cycle, providing an effective method for evaluating the stability of the myocardial infarction region contour segment over a period of time.

[0053] Furthermore, the present invention determines the change amount of the myocardial infarction region contour area of each injury regulation sub-region during the injury identification cycle, transforming the injury development situation of myocardial infarction into quantifiable data. By calculating the difference between the change amounts of the myocardial infarction region contour areas in adjacent injury identification cycles and taking the average as the difference amount, it can acutely capture the subtle change trend in the process of myocardial infarction injury development. Using the difference between the difference amounts of the representative first injury regulation sub-region and the second injury regulation sub-region fully considers the injury expansion differences of myocardial infarction in different parts. Furthermore, it improves the uniformity and effectiveness of the continuous construction of the model. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 It is a step diagram of the in-vitro and in-vivo modeling method for myocardial infarction ischemic injury in an embodiment of the present invention;

[0055] Figure 2 It is a step diagram of determining the confidence of each myocardial infarction region contour segment in an embodiment of the present invention;

[0056] Figure 3 It is a step diagram of determining whether the myocardial infarction ischemic injury sample model is qualified in an embodiment of the present invention;

[0057] Figure 4 It is a logic flow diagram of determining whether the myocardial infarction ischemic injury sample model is qualified; DETAILED DESCRIPTION OF THE EMBODIMENTS [[ID=2,8]]

[0058] In order to make the objectives and advantages of the present invention more clearly understood, the present invention will be further described below in conjunction with embodiments; it should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0059] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are only used to explain the technical principles of the present invention and do not limit the protection scope of the present invention.

[0060] It should be noted that in the description of the present invention, terms indicating directions or positional relationships such as "upper", "lower", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings. This is only for convenience of description and does not indicate or imply that the device or element must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation of the present invention.

[0061] Please refer to Figure 1 As shown, it is a step diagram of the in-vivo and in-vitro modeling method for myocardial infarction ischemic injury in an embodiment of the present invention. An in-vivo and in-vitro modeling method for myocardial infarction ischemic injury of the present invention includes:

[0062] Step S10, ligating the blood supply artery of a mouse to construct an in-vivo model of a myocardial ischemic injury sample, and storing the myocardium of the mouse under hypoxic conditions to construct an in-vitro model of a myocardial ischemic injury sample;

[0063] Specifically, for the construction of the in-vivo model in the present invention, ligating the blood supply artery is selected. For the construction of the in-vitro model, storing the myocardium under hypoxic conditions is selected. The blood supply artery can be ligated with propylene suture. The storage of myocardial cells under hypoxic conditions is also well-known to those skilled in the art and will not be elaborated here.

[0064] Step S20, pre-constructing the blood supply correlation relationship between each myocardial sub-region and each blood supply artery, and determining the injury expansion prediction order of each myocardial sub-region according to the coronary angiography grading of each myocardial sub-region;

[0065] Specifically, constructing the blood supply correlation relationship between each myocardial sub-region and each blood supply artery in the present invention is well-known to those skilled in the art. From an anatomical perspective, the blood supply correlation regions corresponding to the anterior descending branch of the left coronary artery are the anterior wall and anterior septum of the left ventricle. The blood supply correlation regions corresponding to the circumflex branch of the left coronary artery are the lateral wall and posterior lateral wall of the left ventricle. The blood supply correlation regions corresponding to the right coronary artery are the right ventricle, the inferior wall and posterior wall of the left ventricle. This is the prior art and will not be elaborated here.

[0066] Step S30, perform pre-regulation of ischemic injury on each myocardial sub-region, including regulating the blood flow reserve of the blood supply arteries associated with each myocardial sub-region, or regulating the supply amount of antioxidants in each myocardial sub-region;

[0067] Step S40, screen the injury regulation sub-regions based on the predicted order of injury expansion, and obtain the myocardial infarction region contour of each injury regulation sub-region according to the medical images of each injury regulation sub-region that have completed pre-regulation of injury;

[0068] Step S50, determine a number of contour characterization unit vectors according to the myocardial infarction region contour, determine the confidence level of each myocardial infarction region contour segment according to the direction change of the contour characterization unit vector within a preset injury identification period, and resample the myocardial infarction region contour segment with doubtful confidence level to obtain a re-defined myocardial infarction region contour segment;

[0069] Specifically, the duration value of the preset injury identification period can be [0.5h, 3h]. Preferably, the duration value of the injury identification period can be 1h.

[0070] Step S60, determine the difference amount of the injury characterization quantity of each injury regulation sub-region within consecutive injury identification periods based on the myocardial infarction region contour of each injury regulation sub-region, and determine whether the myocardial infarction ischemic injury sample model is qualified based on the difference amount;

[0071] Specifically, in this invention, the myocardial infarction ischemic injury models determined to be qualified are retained for subsequent research and experimental applications, and the myocardial infarction ischemic injury models determined to be unqualified are discarded to avoid the influence of unqualified myocardial infarction ischemic injury models on the results of subsequent research and experimental applications.

[0072] Step S70, conduct GDF-15 research tests on the determined qualified myocardial infarction ischemic injury sample models.

[0073] Specifically, in the GDF-15 research experiment on myocardial infarction ischemic injury sample models, in order to explore the role of GDF-15 in myocardial infarction ischemic injury samples, it is necessary to set up a GDF-15 knockout experimental group and a non-GDF-15 knockout experimental group. When exploring the role of GDF-15 in myocardial infarction ischemic injury samples, setting up knockout and non-knockout experimental groups is a classic and effective research method. By comparing the differences between the two groups, the functional impact of GDF-15 can be clearly and intuitively determined. Ensuring that other interfering factors are consistent except for GDF-15 is the key prerequisite for ensuring the reliability of experimental results. This design conforms to the basic principle of controlling variables in scientific research. Differences in the myocardial infarction ischemic injury sample model itself, such as the unevenness of the infarction area and the inconsistency of the injury development process, may interfere with the determination of GDF-15 research results. By performing infarctions with a uniform rate on the myocardial infarction ischemic injury sample model, the interference caused by differences in the characteristics of the sample model itself can be effectively eliminated, making the experimental results more focused on the role of GDF-15, enabling researchers to more accurately analyze the mechanism of action of GDF-15 in myocardial infarction ischemic injury.

[0074] Specifically, the process of determining the injury expansion prediction order of each myocardial sub-region includes:

[0075] Pre-obtain the coronary angiography grades of each myocardial sub-region, and sort each myocardial sub-region in ascending order according to the coronary angiography grades;

[0076] Determine the sorting order of each myocardial sub-region as the injury expansion prediction order of each myocardial sub-region.

[0077] Specifically, by determining the injury expansion prediction order, the present invention can clarify the speed order of infarct area expansion in different myocardial sub-regions, thereby providing a reasonable basis for subsequent pre-regulation of ischemic injury in each myocardial sub-region, facilitating targeted regulation according to the characteristics of different regions. It can be understood that through coronary angiography grading, the stenosis degree, occlusion situation, etc. of the coronary artery vessels corresponding to each myocardial sub-region can be graded. The higher the grade, the relatively lighter the stenosis or occlusion of the coronary artery vessels. Based on the relationship between the above coronary angiography grading and the infarct area expansion speed of myocardial sub-regions, sorting each myocardial sub-region in ascending order according to the coronary angiography grades is actually arranging them in the order of infarct area expansion of myocardial sub-regions from fast to slow. The order and relative speed of injury expansion of each myocardial sub-region in the entire myocardial infarction ischemic injury process are clearly determined, so as to conduct targeted research, analysis and regulation according to the injury expansion characteristics of different myocardial sub-regions in the subsequent process, achieving the prediction of injury expansion in the infarct area during the continuous batch construction of myocardial infarction ischemic injury models.

[0078] Specifically, the coronary angiography grading mainly evaluates the degree of coronary artery stenosis and other conditions, including high-precision image acquisition and dynamic tracking of contrast agents, and determines the coronary angiography grading through collateral circulation grading. The coronary angiography grading is carried out according to the following table:

[0079] Grade Feature Proportion of collateral flow 0 No collateral visualization ＜10％ 1 Collaterals only fill branch vessels 10-25％ 2 Partial epicardial vessel visualization 25-50％ 3 Collaterals completely connect the occluded area ＞50％

[0080] Specifically, the process of selecting the injury pre-regulation for ischemic injury includes:

[0081] If the current myocardial infarction ischemic injury model is an in-vivo modeling method, then select the reserve amount of regulating the blood flow reserve of the blood supply arteries associated with each myocardial sub-region;

[0082] If the current myocardial infarction ischemic injury model is an in-vitro modeling method, then select the supply amount of regulating antioxidants for each myocardial sub-region.

[0083] Specifically, it can be understood that in vivo, the blood supply of the myocardium is achieved through the blood supply arteries. When the blood flow reserve of the blood supply arteries changes, it will directly affect the blood perfusion of the myocardial sub-regions. By regulating the blood flow reserve of the blood supply arteries, the ischemic degree of different myocardial sub-regions during the development of myocardial infarction can be regulated, and then the injury process can be controlled. In vitro, when culturing myocardial cells or myocardial tissues in vitro, when the myocardial cells are in an environment of hypoxia and other simulated ischemia, the redox balance in the cells will be disrupted, and a large amount of reactive oxygen species (ROS) will be generated. These ROS will attack biological macromolecules such as the cell membrane, proteins, and nucleic acids of myocardial cells, resulting in lipid peroxidation of the cell membrane, protein denaturation, DNA damage, etc., and then causing the injury and death of myocardial cells. By regulating the supply amount of antioxidants for each myocardial sub-region, the ischemic degree of different myocardial sub-regions during the development of myocardial infarction can be controlled, and the control of the injury process can be achieved.

[0084] Specifically, determine the reserve amount of regulating the blood flow reserve of the blood supply arteries associated with each myocardial sub-region and the supply amount of regulating antioxidants for each myocardial sub-region according to the injury expansion prediction order;

[0085] Among them, the reserve amount of the blood flow reserve decreases successively according to the injury expansion prediction order, and the supply amount of the antioxidant decreases successively according to the injury expansion prediction order.

[0086] Specifically, in the in-vivo modeling method of the present invention, when regulating the blood flow reserve of the blood supply arteries associated with each myocardial sub-region, it can be understood that the blood flow reserve is regulated according to the order of injury dilation prediction. This is because different myocardial sub-regions have different sensitivities to ischemia and different rates of injury dilation due to their different coronary angiography grades. The myocardial sub-region with a higher order in the injury dilation prediction indicates that it is more likely to be damaged and has a faster dilation rate under ischemic conditions, so a relatively larger blood flow reserve is given. For the region with a slower infarction dilation, the regulation amount is reduced. This can make the myocardium in different regions be evenly damaged during the ischemic injury process. Similarly, the supply amount of antioxidants is sequentially reduced according to the order of injury dilation prediction because the myocardial sub-region with a higher order in the injury dilation prediction has a relatively faster injury dilation rate and requires more antioxidants to slow down the injury rate. This can make the myocardium in different regions be evenly damaged during the ischemic injury process. Furthermore, the process of model construction is targeted regulated.

[0087] Specifically, the process of screening the injury regulation sub-regions includes:

[0088] Determining the myocardial sub-regions corresponding to the first and last positions in the injury dilation prediction order based on the injury dilation prediction order of each myocardial sub-region;

[0089] Respectively screening the myocardial sub-regions corresponding to the first order and the last order as the injury regulation sub-regions;

[0090] Among them, the myocardial sub-region corresponding to the first order is screened as the first characteristic sub-region of injury regulation, and the myocardial sub-region corresponding to the last order is screened as the second characteristic sub-region of injury regulation.

[0091] In the present invention, the myocardial sub-regions corresponding to the first and last positions in the injury dilation prediction order are screened as the injury regulation sub-regions because these two regions represent two extreme situations in the injury dilation process. Selecting these two regions for key research and regulation can take more targeted treatment or intervention measures for regions with different characteristics, and make the model construction of myocardial infarction ischemic injury more uniform and stable by regulating the injury progress of each region.

[0092] Specifically, the present invention screens the myocardial sub-regions corresponding to the first and last positions in the injury dilation prediction order as the injury regulation sub-regions, which can accurately locate the regions with the fastest and slowest infarction dilations. By comparing and analyzing these two characteristic sub-regions with obvious differences, the pathophysiological mechanisms of myocardial infarction at different stages and different dilation rates can be better understood, and the process of model construction is targeted regulated.

[0093] Specifically, the process of obtaining the myocardial infarction region contour of each injury regulation sub-region includes:

[0094] Obtain the medical images of the first injury regulation characteristic sub-region and the second injury regulation characteristic sub-region, and remove noise from the medical images and correct the image gray scale;

[0095] Using an image segmentation algorithm and an edge detection algorithm, determine the contour of the first myocardial infarction region within the first injury regulation characteristic sub-region, and determine the contour of the second myocardial infarction region within the second injury regulation characteristic sub-region.

[0096] In implementation, using an image segmentation algorithm and an edge detection algorithm to determine the region contour is a prior art and will not be elaborated here.

[0097] Specifically, determining the contour representation unit vectors includes:

[0098] Respectively determine the contour centroid corresponding to the start moment of the injury identification cycle of the first myocardial infarction region contour and the contour centroid corresponding to the start moment of the injury identification cycle of the second myocardial infarction region contour;

[0099] Respectively construct the contour representation unit vectors of the first myocardial infarction region contour and the second myocardial infarction region contour;

[0100] Among them, the contour representation unit vector of the first myocardial infarction region contour takes the contour centroid of the first myocardial infarction region contour as the vector starting point, and respectively takes a number of marked points set on the first myocardial infarction region contour as the vector end points, and the contour representation unit vector of the second myocardial infarction region contour takes the contour centroid of the second myocardial infarction region contour as the vector starting point, and respectively takes a number of marked points set on the second myocardial infarction region contour as the vector end points.

[0101] Specifically, the present invention determines the contour centroid of the myocardial infarction region contour at the start moment of the injury identification cycle, and takes this as the starting point, sets marked points on the contour to construct the contour representation unit vectors, converts the complex geometric shape of the myocardial infarction region contour into a set of quantifiable vector data, constructs vectors based on the contour centroid, can reflect both the overall shape and local details of the myocardial infarction region contour at the same time, the contour centroid represents the geometric center of the contour, the vectors from the centroid to each marked point not only reflect the relative position relationship between each part of the contour and the whole, but also can reflect the deformation of the local contour through the change of the vectors, which helps to comprehensively grasp the development and change of the myocardial infarction region, sets a confidence threshold to determine whether the confidence of the contour segment is in doubt, and re-samples and contour fits the contour segments with confidence lower than the threshold, which can effectively correct the possibly inaccurate contour definition, and realizes the targeted regulation of the model construction process.

[0102] Specifically, please refer to Figure 2As shown in the figure. It is a step diagram for determining the confidence of each myocardial infarction area contour segment in the embodiments of the present invention. The process of determining the confidence of each myocardial infarction area contour segment includes:

[0103] Step S51: Based on the vector end point of the contour representation unit vector, determine a myocardial infarction area contour segment with a preset length on the myocardial infarction area contour;

[0104] Step S52: Determine the vector included angles of each contour representation unit vector at the start and end times of the injury identification period;

[0105] Step S53: Determine the reciprocal of the vector included angle as the confidence of the myocardial infarction area contour segment corresponding to the contour representation unit vector.

[0106] Specifically, the value range of the preset length of the myocardial infarction area contour segment can be [1, 3], and the interval unit is mm. The smaller the set length of the myocardial infarction area contour segment, the more accurate the constructed myocardial infarction area contour. Those skilled in the art can set the length of the myocardial infarction area contour segment on the basis of meeting the model construction requirements. Preferably, the preset length of the myocardial infarction area contour is 2 mm.

[0107] Specifically, the present invention determines a contour segment with a preset length based on the end point of the contour representation unit vector, and determines the confidence by calculating the reciprocal of the included angle of the vector at the start and end times of the injury identification period, providing an effective method for evaluating the stability of the myocardial infarction area contour segment over a period of time.

[0108] Specifically, the process of determining the myocardial infarction area contour segment with doubtful confidence and obtaining the redefined myocardial infarction area contour segment includes:

[0109] If the confidence of the myocardial infarction area contour segment meets the contour construction confidence requirement, it is determined that the confidence of the myocardial infarction area contour segment is not doubtful;

[0110] If the confidence of the myocardial infarction area contour segment does not meet the contour construction confidence requirement, it is determined that the confidence of the myocardial infarction area contour segment is doubtful;

[0111] Resample the myocardial infarction area contour segment with doubtful confidence, perform contour fitting on the myocardial infarction area contour segment obtained by resampling and the myocardial infarction area contour segment with doubtful confidence, and obtain the redefined myocardial infarction area contour segment;

[0112] Among them, the contour construction confidence requirement is that the confidence is lower than the preset confidence threshold.

[0113] Specifically, the present invention does not limit the specific method of achieving contour fitting between the resampled myocardial infarction area contour segment and the myocardial infarction area contour segment with questionable confidence. Preferably, a Bezier curve adaptive fitting algorithm can be used to achieve curve fitting of the contour segment. This is an existing technology and will not be repeated here.

[0114] In practice, the preset confidence threshold is determined based on historical experimental data. The vector angles of the corresponding contour representation unit vectors of each myocardial infarction area contour segment of the myocardial infarction ischemia model of the same animal are obtained in advance under multiple sampling, and the confidence threshold is determined based on the average value of several vector angles. The specific experimental data are as follows:

[0115]

[0116] It can be seen from the above experimental data records that the lower the preset confidence threshold, the more contour segments of the myocardial infarction area need to be resampled and refitted, and the obtained contour segments are more accurate, but the more computing power is required. Preferably, the preset confidence threshold value of the present invention can be 0.09.

[0117] Specifically, the present invention does not limit the sampling method for resampling the contour segments of the myocardial infarction area with questionable confidence. Preferably, it can be resampled based on contour features. In areas with larger curvature, that is, where the contour is more curved, the density of sampling points is increased. It can also be resampled based on image grayscale. For example, for a point with a grayscale value lower than a threshold, if there are multiple points above the threshold around it, it can be discarded; for an area with a grayscale value higher than the threshold, the density of sampling points can be appropriately increased to more accurately define the boundary of the myocardial infarction area. Resampling based on contour features or based on image grayscale is a prior art and will not be described in detail here.

[0118] Specifically, see Figure 3 As shown in FIG, it is a step diagram of determining whether a myocardial infarction ischemic injury sample model is qualified according to an embodiment of the present invention. The process of determining whether a myocardial infarction ischemic injury sample model is qualified includes:

[0119] Step S61, determining the myocardial infarction region contours of each damage control sub-region at the start and end times of the damage identification cycle, and determining the area change of the myocardial infarction region contours within the damage identification cycle based on the pixel areas;

[0120] Step S62, calculating the difference in the change in the contour area of the myocardial infarction region between adjacent injury identification cycles, and determining the average value of the plurality of differences as the difference;

[0121] Step S63: Determine whether the myocardial infarction ischemia injury sample model is qualified based on the comparison result between the difference quantity comparison value and the preset identification error reference value;

[0122] Among them, please refer to Figure 4 As shown, it is a logic flow chart for determining whether the myocardial infarction ischemia injury sample model is qualified. If the difference quantity comparison value exceeds the identification error reference value, it is determined that the current myocardial infarction ischemia injury model is unqualified. If the difference quantity comparison value does not exceed the identification error reference value, it is determined that the current myocardial infarction ischemia injury model is qualified. The difference quantity comparison value is the difference between the difference quantity of the first myocardial infarction region contour and the difference quantity of the second myocardial infarction region contour.

[0123] Specifically, the pixel resolution of the image can be determined, that is, the area size represented by each pixel point in the actual physical space, the pixel points within the extracted myocardial infarction region contour are counted, and then multiplied by the area of a single pixel point to obtain the contour area of the myocardial infarction region. This is prior art and will not be elaborated here.

[0124] In implementation, the preset identification error reference value can be determined based on historical data. The difference quantity of the change in the contour area of the first myocardial infarction region in several adjacent injury identification cycles and the difference quantity of the change in the contour area of the second myocardial infarction region in several adjacent injury identification cycles are determined in advance, and the preset identification error reference value is determined according to the difference quantity of the change in the contour area of the first myocardial infarction region and the difference quantity of the change in the contour area of the second myocardial infarction region;

[0125] In implementation, the following 10 groups of experimental historical data are obtained in advance;

[0126]

[0127]

[0128] The average value of these difference quantity comparison values is calculated to be 0.06. The preset identification error reference value can be the product of the average value of the difference quantity comparison values and the value coefficient. The value range of the value coefficient is [1, 1.3]. Preferably, the value coefficient is set to 1.25, then the preset identification error reference value is 0.06 × 1.25 = 0.075.

[0129] Specifically, the present invention determines the change amount of the contour area of the myocardial infarction region in each injury regulation sub-region during the injury identification period, converts the injury development situation of myocardial infarction into quantifiable data, calculates the difference between the change amounts of the contour areas of the myocardial infarction regions in adjacent injury identification periods, and takes the average value as the difference amount, which can sensitively capture the subtle change trend in the process of myocardial infarction injury development. By using the difference between the difference amounts of the representative first injury regulation sub-region and the second injury regulation sub-region, the injury expansion differences of myocardial infarction in different parts are fully considered. Furthermore, the uniformity and effectiveness of the continuous construction of the model are improved.

[0130] Exemplarily, here are provided 5 experimental groups for injury regulation using the present invention and 5 control groups without using the present invention for injury regulation. 10 mice are selected for sample modeling in each experimental group and each control group. The experimental data of each experimental group and each control group are as follows:

[0131]

[0132] From the above experimental data, it can be seen that the standard deviation of the infarct area of the 5 control groups without using the present invention for injury regulation is between 3.0 - 3.5 mm 2 and the difference in infarct area between samples is relatively large. The standard deviation of the infarct area of the 5 experimental groups using the present invention for injury regulation is between 0.9 - 1.3 mm 2 and the difference in infarct area between samples is significantly reduced, and the sample uniformity is improved. In the GDF-15 research experiment, a model with high sample uniformity can more accurately reflect the therapeutic effect of GDF-15 on myocardial infarction.

[0133] So far, the technical solution of the present invention has been described in combination with the preferred embodiments shown in the drawings. However, it is easy for those skilled in the art to understand that the protection scope of the present invention is obviously not limited to these specific embodiments. Without departing from the principle of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will all fall within the protection scope of the present invention.

[0134] The above are only the preferred embodiments of the present invention and are not used to limit the present invention; for those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for modeling myocardial infarction ischemic injury in vivo and in vitro, characterized in that: include: The blood supply arteries of mice were ligated to establish an in vivo model of myocardial ischemic injury, and the myocardium of mice was stored under hypoxic conditions to establish an in vitro model of myocardial ischemic injury; The blood supply correlation between each myocardial sub-region and each blood supply artery is pre-established, and the damage expansion prediction order of each myocardial sub-region is determined according to the coronary angiography grade of each myocardial sub-region; Pre-regulating the ischemic damage of each myocardial subregion, including regulating the blood flow reserve of the blood supply artery associated with each myocardial subregion, or regulating the supply of antioxidants to each myocardial subregion; selecting the damage control sub-regions based on the damage expansion prediction order, and obtaining the myocardial infarction area contours of each damage control sub-region according to the medical images of each damage control sub-region after completing the damage pre-control; Determining a plurality of contour characterization unit vectors based on the myocardial infarction region contour, determining the confidence of each myocardial infarction region contour segment based on the direction change of the contour characterization unit vectors within a preset injury identification cycle, and resampling the myocardial infarction region contour segments with questionable confidence to obtain redefined myocardial infarction region contour segments; Determining differences in damage characterization quantities of each damage regulation sub-region within consecutive damage identification cycles based on the myocardial infarction region contours of each damage regulation sub-region, and determining whether the myocardial infarction ischemic injury sample model is qualified based on the differences; The qualified myocardial infarction ischemic injury sample model was subjected to GDF-15 research experiment.

2. The in vitro and in vivo modeling method of myocardial infarction ischemic injury according to claim 1, characterized in that: The process of determining the predicted order of lesion expansion for each myocardial subregion includes: Pre-acquiring the coronary angiography grade of each myocardial subregion, and sorting the myocardial subregions in ascending order according to the coronary angiography grade; The ranking order of each myocardial sub-region is determined as the predicted order of lesion expansion of each myocardial sub-region.

3. The in vitro and in vivo modeling method of myocardial infarction ischemic injury according to claim 2, characterized in that: The process of selecting for pre-conditioning of ischemic injury includes: If the current myocardial infarction ischemic injury model is an in vivo modeling method, the reserve amount of the blood flow reserve of the blood supply artery associated with each myocardial sub-region is selected; If the current myocardial infarction ischemic injury model is an in vitro modeling method, it is selected to regulate the supply of antioxidants to each myocardial sub-region.

4. The in vitro and in vivo modeling method of myocardial infarction ischemic injury according to claim 3, characterized in that: determining the amount of blood flow reserve for the blood supply arteries associated with each myocardial subregion and regulating the amount of antioxidant supply to each myocardial subregion according to the predicted order of damage expansion; The amount of the blood flow reserve decreases in sequence according to the predicted order of damage expansion, and the amount of the antioxidant supplied decreases in sequence according to the predicted order of damage expansion.

5. The in vitro and in vivo modeling method of myocardial infarction ischemic injury according to claim 2, characterized in that: The process of screening damage regulatory subregions includes: Determining the myocardial subregions corresponding to the first and last positions in the damage expansion prediction order according to the damage expansion prediction order of each myocardial subregion; The myocardial subregions corresponding to the first and last order are respectively selected as the damage regulation subregions; Among them, the myocardial sub-region corresponding to the first order is screened as the first characteristic sub-region of damage regulation, and the myocardial sub-region corresponding to the last order is screened as the second characteristic sub-region of damage regulation.

6. The in vitro and in vivo modeling method of myocardial infarction ischemic injury according to claim 5, characterized in that: The process of obtaining the contour of the myocardial infarction area in each damage regulation subregion includes: Acquire medical images of the first characteristic sub-region of damage regulation and the second characteristic sub-region of damage regulation, and remove noise from the medical images and correct image grayscale; An image segmentation algorithm and an edge detection algorithm are used to determine the outline of the first myocardial infarction region within the first characteristic sub-region of damage regulation, and to determine the outline of the second myocardial infarction region within the second characteristic sub-region of damage regulation.

7. The in vitro and in vivo modeling method of myocardial infarction ischemic injury according to claim 6, characterized in that: Determining the contour characterization unit vector includes: respectively determining a contour centroid of the first myocardial infarction region contour corresponding to the start time of the lesion identification cycle and a contour centroid of the second myocardial infarction region contour corresponding to the start time of the lesion identification cycle; Constructing contour representation unit vectors of the first myocardial infarction area contour and the second myocardial infarction area contour respectively; Among them, the contour representation unit vector of the first myocardial infarction area contour takes the contour centroid of the first myocardial infarction area contour as the vector starting point, and takes several marking points set on the first myocardial infarction area contour as the vector end point. The contour representation unit vector of the second myocardial infarction area contour takes the contour centroid of the second myocardial infarction area contour as the vector starting point, and takes several marking points set on the second myocardial infarction area contour as the vector end point.

8. The in vitro and in vivo modeling method of myocardial infarction ischemic injury according to claim 7, characterized in that: The process of determining the confidence level of each myocardial infarction area contour segment includes: Determining a myocardial infarction region contour segment of a preset length on the myocardial infarction region contour, taking the vector end point of the contour representation unit vector as a reference; Determine the vector angles of each contour characterization unit vector at the start and end of the damage identification cycle; The reciprocal of the vector angle is determined as the confidence level of the contour segment of the myocardial infarction region corresponding to the contour representation unit vector.

9. The in vitro and in vivo modeling method for myocardial infarction ischemic injury according to claim 8, characterized in that: The process of determining the contour segment of the myocardial infarction area with questionable confidence and obtaining the redefined contour segment of the myocardial infarction area includes: If the confidence level of the myocardial infarction region contour segment does not meet the contour construction confidence level requirement, it is determined that the confidence level of the myocardial infarction region contour segment is questionable; Resampling the contour segment of the myocardial infarction area with questionable confidence, performing contour fitting between the resampled contour segment of the myocardial infarction area and the contour segment of the myocardial infarction area with questionable confidence, and obtaining a redefined contour segment of the myocardial infarction area; The outline construction confidence requirement is that the confidence is lower than a preset confidence threshold.

10. The in vitro and in vivo modeling method for myocardial infarction ischemic injury according to claim 9, characterized in that: The process of determining whether the myocardial infarction ischemic injury sample model is qualified includes: Determining the myocardial infarction region contours of each damage control sub-region at the start and end of the damage identification cycle, and determining the area change of the myocardial infarction region contours within the damage identification cycle based on the pixel area; Calculating the difference in the change in the contour area of the myocardial infarction region between adjacent injury identification cycles, and determining the average of several differences as the difference amount; Based on the comparison result of the difference comparison value and the preset identification error reference value, it is determined whether the myocardial infarction ischemic injury sample model is qualified; Among them, if the difference comparison value exceeds the identification error reference value, the current myocardial infarction ischemic damage model is judged to be unqualified; if the difference comparison value does not exceed the identification error reference value, the current myocardial infarction ischemic damage model is judged to be qualified, and the difference comparison value is the difference between the difference of the first myocardial infarction area contour and the difference of the second myocardial infarction area contour.

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