多尺度循环系统数学模型研究
发布时间：2019-05-21 22:07
【摘要】：心血管疾病是全球死亡率最高的疾病之一,其病理研究、早期预防和临床诊治是一项十分艰巨的工作。循环系统的数学模型可为心血管系统生理研究、心血管疾病的诊断和治疗提供了一种有效的辅助手段。多尺度循环系统数学模型主要研究系统、器官和组织层次循环系统模型耦合中的多物理场问题和多种维度建模技术问题。建立多尺度的循环系统数学模型,能够帮助定量分析循环系统各个层次上的生理和病理特性,提高心血管疾病的预防、诊断与治疗水平。 本文的研究目标是通过对不同层次循环系统建模中关键技术问题的研究,建立多尺度循环系统数学模型。具体完成了以下工作： 1、解决了循环系统多尺度模型研究中的关键技术问题,包括(1)仿真心率变异性的自主神经系统模型技术；(2)提高一维(One-Dimensional,1D)微循环模型仿真效率的数值计算技术；(3)整体循环系统与微循环系统的耦合技术。 2、建立了整体循环系统与自主神经系统耦合模型,基于该模型提出了一种表征副交感神经活动的特异性参数。应用临床数据初步验证了该参数的有效性,并基于模型分析了其生理机制。 3、建立了基于大鼠肠系膜实验数据的微循环系统1D模型,仿真了血流脉动性的衰减特性。基于模式动物实验验证了模型的有效性。应用该模型发现微血管的阻力与顺应性是血流脉动性衰减的主要原因。 4、基于结构参数耦合了整体循环与微循环系统模型,仿真发现微循环结构性病变会改变整体血压水平。仿真结果还表明,高血压情况下外周血压脉动性降低,并影响微循环功能。 在上述工作中,本文研究的创新点在于： 1、提出了基于血管阻力及顺应性耦合的多尺度模型技术,有效地解决了整体循环与微循环系统模型结合的问题,为仿真研究血流动力学与功能特性的融合提供了有益的探索。 2、基于结合自主神经调节机制的整体循环模型研究,提出了一种改进的心率减速能力参数,并借助模型阐明了算法改进的机理,为促进自主神经系统评价指标的临床应用提供了一种新的方法。 3、提出了1D微循环系统建模中高效的数值计算方法,所建立的模型可系统地仿真血流脉动性衰减现象,改变了微循环血流脉动性衰减机制研究中缺乏技术手段的现状,为研究微循环中血流脉动性介导的机械信号转导过程提供了崭新的平台。 本文所建立的多尺度循环系统数学模型为循环系统生理和病理研究提供了有效的定量研究技术平台,待其完善并应用后将有益于促进心血管疾病基础研究,提升国民心血管健康水平。
[Abstract]:Cardiovascular disease is one of the highest mortality diseases in the world. Its pathological research, early prevention and clinical diagnosis and treatment is a very difficult task. The mathematical model of circulatory system can provide an effective auxiliary means for the study of cardiovascular system physiology and the diagnosis and treatment of cardiovascular diseases. The mathematical model of multi-scale circulation system mainly studies the multi-physical field problem and multi-dimensional modeling technology in the coupling of system, organ and tissue hierarchical circulation system model. The establishment of multi-scale mathematical model of circulatory system can help to quantitatively analyze the physiological and pathological characteristics of circulatory system at all levels and improve the prevention, diagnosis and treatment of cardiovascular diseases. The research goal of this paper is to establish the mathematical model of multi-scale circulation system by studying the key technical problems in the modeling of different levels of circulation system. The main work is as follows: 1. The key technical problems in the study of multi-scale model of circulatory system are solved, including (1) the autonomic nervous system model technology to simulate heart rate variability; (2) the numerical calculation technology to improve the simulation efficiency of one-dimensional (One-Dimensional,1D) microcirculatory model, and (3) the coupling technology of the whole circulation system and the microcirculatory system. 2. A coupling model of global circulatory system and autonomic nervous system was established, and a specific parameter to characterize parasympathetic nerve activity was proposed based on the model. The validity of the parameter was preliminarily verified by clinical data, and its physiological mechanism was analyzed based on the model. 3. The 1D model of microcirculatory system based on rat mesenteric experimental data was established, and the attenuation characteristics of blood flow pulsation were simulated. The effectiveness of the model is verified by model-based animal experiments. Using this model, it is found that the resistance and compliance of microvessels are the main reasons for the pulsatile attenuation of blood flow. 4. Based on the structural parameters, the model of global circulation and microcirculatory system is coupled, and it is found that the structural lesion of microcirculation will change the level of global blood pressure. The simulation results also show that the pulsation of peripheral blood pressure decreases and affects the function of microcirculatory in the case of hypertension. In the above work, the innovations of this paper are as follows: 1. A multi-scale model technology based on the coupling of vascular resistance and compliance is proposed, which effectively solves the problem of the combination of the whole circulation and the microcirculatory system model. It provides a useful exploration for the simulation study of the fusion of hemodynamics and functional characteristics. 2. Based on the research of global circulation model combined with autonomic nerve regulation mechanism, an improved heart rate deceleration ability parameter is proposed, and the mechanism of algorithm improvement is expounded with the help of the model. It provides a new method for promoting the clinical application of autonomic nervous system evaluation index. 3. An efficient numerical calculation method in 1D microcirculatory system modeling is proposed. The established model can systematically simulate the phenomenon of blood flow pulsation attenuation, which changes the present situation of the lack of technical means in the study of the mechanism of circulatory blood flow pulsation attenuation. It provides a new platform for studying the mechanical signal transduction process mediated by blood flow pulsation in microcirculation. The mathematical model of multi-scale circulatory system established in this paper provides an effective quantitative research technical platform for physiological and pathological research of circulatory system, and when it is perfected and applied, it will be beneficial to promote the basic research of cardiovascular diseases. Improve the level of cardiovascular health of the people.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R311
本文编号：2482439
[Abstract]:Cardiovascular disease is one of the highest mortality diseases in the world. Its pathological research, early prevention and clinical diagnosis and treatment is a very difficult task. The mathematical model of circulatory system can provide an effective auxiliary means for the study of cardiovascular system physiology and the diagnosis and treatment of cardiovascular diseases. The mathematical model of multi-scale circulation system mainly studies the multi-physical field problem and multi-dimensional modeling technology in the coupling of system, organ and tissue hierarchical circulation system model. The establishment of multi-scale mathematical model of circulatory system can help to quantitatively analyze the physiological and pathological characteristics of circulatory system at all levels and improve the prevention, diagnosis and treatment of cardiovascular diseases. The research goal of this paper is to establish the mathematical model of multi-scale circulation system by studying the key technical problems in the modeling of different levels of circulation system. The main work is as follows: 1. The key technical problems in the study of multi-scale model of circulatory system are solved, including (1) the autonomic nervous system model technology to simulate heart rate variability; (2) the numerical calculation technology to improve the simulation efficiency of one-dimensional (One-Dimensional,1D) microcirculatory model, and (3) the coupling technology of the whole circulation system and the microcirculatory system. 2. A coupling model of global circulatory system and autonomic nervous system was established, and a specific parameter to characterize parasympathetic nerve activity was proposed based on the model. The validity of the parameter was preliminarily verified by clinical data, and its physiological mechanism was analyzed based on the model. 3. The 1D model of microcirculatory system based on rat mesenteric experimental data was established, and the attenuation characteristics of blood flow pulsation were simulated. The effectiveness of the model is verified by model-based animal experiments. Using this model, it is found that the resistance and compliance of microvessels are the main reasons for the pulsatile attenuation of blood flow. 4. Based on the structural parameters, the model of global circulation and microcirculatory system is coupled, and it is found that the structural lesion of microcirculation will change the level of global blood pressure. The simulation results also show that the pulsation of peripheral blood pressure decreases and affects the function of microcirculatory in the case of hypertension. In the above work, the innovations of this paper are as follows: 1. A multi-scale model technology based on the coupling of vascular resistance and compliance is proposed, which effectively solves the problem of the combination of the whole circulation and the microcirculatory system model. It provides a useful exploration for the simulation study of the fusion of hemodynamics and functional characteristics. 2. Based on the research of global circulation model combined with autonomic nerve regulation mechanism, an improved heart rate deceleration ability parameter is proposed, and the mechanism of algorithm improvement is expounded with the help of the model. It provides a new method for promoting the clinical application of autonomic nervous system evaluation index. 3. An efficient numerical calculation method in 1D microcirculatory system modeling is proposed. The established model can systematically simulate the phenomenon of blood flow pulsation attenuation, which changes the present situation of the lack of technical means in the study of the mechanism of circulatory blood flow pulsation attenuation. It provides a new platform for studying the mechanical signal transduction process mediated by blood flow pulsation in microcirculation. The mathematical model of multi-scale circulatory system established in this paper provides an effective quantitative research technical platform for physiological and pathological research of circulatory system, and when it is perfected and applied, it will be beneficial to promote the basic research of cardiovascular diseases. Improve the level of cardiovascular health of the people.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R311
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