医学微气泡的约束振动理论及分析方法
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摘要
医学微气泡在超声造影、定点送药、冲击波碎石等超声医学治疗技术中,已经得了到广泛应用,但气泡振动及破裂过程中容易引起病人的肾组织和心血管系统受损,造成严重的医疗事故。因此,开展医用气泡的约束振动研究,具有非常重要的理论意义和临床应用价值。本文运用流固耦合振动原理,借助流体力学计算方法,研究了医用气泡的非球对称振动特征,分析了微血管的动态响应机理。获得的主要创造性新成果有:
(1)提出了超声造影剂的双层结构理论及其分析方法。为了使得造影剂既有优良的散射特征,又具有足够的可靠性,我们提出了双层壳型超声造影剂结构,并建立了双层壳的散射率-频率关系。利用所得到的散射率函数,计算并分析了外层壳的厚度、材料参数、粘性阻尼等对双层壳散射特征的影响。结果表明,恰当形式的软外层壳,能够极大地改善结构的散射特征。
(2)根据体外实验所观察到的现象,提出了气泡的旋转椭球面假设,据此建立了约束气泡的非球对称振动模型。开展了约束气泡振动分析。计算发现,气泡的演化规律与流体的出入口边界条件和固体管壁的约束条件密切相关。管壁的约束会引起气泡振动时出现强烈的非对称效应,并导致内壁压力峰值显著增加,而这些在用Rayleigh-Plesset方程计算时被明显忽略和低估了。
(3)建立了真实血管约束下的气泡-血液-管壁三相耦联动力学模型。考虑了管壁的惯性效应和柔性影响。计算结果表明,管壁越薄、环向刚度越大、初始血压越高,则气泡的非对称效应越强,管壁内的应力波动幅度也越大。因此老人、儿童和某些疾病病人(心血管病人、糖尿病人等)在超声波辅助治疗时危险性更高。
(4)研究了血液粘性对约束气泡振动的影响,证明了气泡的非对称振动模态是造成管壁损伤的主要原因,并且发现沿环向撕裂是其主要破坏形式。
(5)提出了双层微血管约束下的气泡动力学模型,并据此分析了气泡的非对称振动特征和壳壁应力的变化规律。计算发现,在气泡-血管耦合振动过程中,当内层壳的刚度增加时,尽管气泡的非对称振动效应以及流体对管壁的冲击幅度都变化不大,但是内膜层的环向应力却急剧增加。这一结果说明,血管硬化病人,在超声波碎石等治疗中,比正常人存在更大的风险。
本文系统地建立了伪弹性微管约束下的气-液-固耦联动力学模型,深入研究了气泡的非对称振动特征、血液的粘性效应、管壁材料的性质以及尺寸等对管壁应力和变形的影响规律,证明了气泡的非对称振动模态是造成管壁损伤的主要原因,发现了沿环向撕裂是其主要的破坏形式。这些对于设计有效的预防措施,安全使用超声碎石技术和定点送药技术等具有非常重要的理论意义和应用价值。
Medical bubbles have been widely applied in ultrasonic imaging (UI), targeted drug delivery (TDD) and shock wave lithotripsy (SWL). But for subgroup patients in these treatments, the injuries of renal tissue and vascular system are caused by bubbles oscillating and rupturing. Therefore, it has theoretical and clinical importance to explore the constraint oscillation mechanicsm of medical microbubbles. In this dissertation, by using the principle of liquid-solid coupled vibration and the method of computational fluid dynamics, the non-spherical oscillation characteristics of a medical microbubble and the corresponding dynamic responses of a micro blood vessel are investigated. Specific innovative contents are as follows:
(1) Double-layered structural theory of the ultrasound contrast agent (UCA) and its analysis method are introduced. To obtain excellent scattering ratio and sufficient reliability in UCA, we propose a new double-layered spherical shell structure and obtain the relationship between reflectivity and frequency. We also calculate and analyze the effects of thickness, material coefficients and viscoelastic damping of outer shell on the scattering characteristics of the structure. The results show scattering features of the double-layered shell are remarkably improved by an appropriate soft outer shell in UI.
(2) We present an ellipsoidal evolving model of constrained bubble according to the experimental observation in vivo, and construct an asysmmetric oscillation theory to analyze a non-spherical bubble. Computational results show that oscillating bubble profile depends on the liquid and solid boundary conditions, and indicate that the asymmetric effects of bubble oscillation due to the vessel constraint lead to a larger pressure exerted on the vessel, which is obviously underestimated or ignored by the Rayleigh–Plesset equation.
(3) We propose a three-phase dynamic model of a bubble-blood-vessel coupled oscillation system with a real constraint blood vessel. Inertial effect and compliance effect of the microvessel are taken into account. Calculated results show that a vessel wall with the thinner vessel or larger circumferential stiffness or higher pre-existing blood pressure correspond to the stronger bubble asymmetric measure and larger vessel stress amplitude. Thus elders, children and some special subjects such as cardiovascular and diabete patients, are higher risk in assisted therapy involving shock waves.
(4) The blood viscosity effects in course of constrained bubble oscillating are investigated. It has been proved that asymmetrical oscillation mode is a primary factor for vascular injury and circumferentially tearing is the dominant rupture mode.
(5) A new dynamic model about a bubble confined inside a double-layer micovessel is proposed, and then the asymmetric oscillation characterists of the microbubble and the regarding stress changes of the vessel are analyzed. It exhibits inconspicuous fluctuation with the asymmetrical scale of bubble oscillation and the liquid pressure exerted on the vessel wall, however, the corresponding dynamic circumferential stress of inner intima layer is increasing acutely. These conclusions indicate that the atherosclerotic patients have a higher risk in SWL.
We systematically propose and develop a bubble-liquid-vessel dynamic coupled model about constrained microbubble oscillation inside a micro pseudoelastic blood vessel, and investigate various effects on stresses and deformation of a vessel wall including asymmetric bubble oscillation, blood viscocity and vessel material and geometric papameters. We also prove that asymmetrical oscillation is a primary factor for vascular injury and circumferentially tearing is the dominant rupture mode. These conclusions have significant theory and application importances in safety of TDD and SWL.
(1)提出了超声造影剂的双层结构理论及其分析方法。为了使得造影剂既有优良的散射特征,又具有足够的可靠性,我们提出了双层壳型超声造影剂结构,并建立了双层壳的散射率-频率关系。利用所得到的散射率函数,计算并分析了外层壳的厚度、材料参数、粘性阻尼等对双层壳散射特征的影响。结果表明,恰当形式的软外层壳,能够极大地改善结构的散射特征。
(2)根据体外实验所观察到的现象,提出了气泡的旋转椭球面假设,据此建立了约束气泡的非球对称振动模型。开展了约束气泡振动分析。计算发现,气泡的演化规律与流体的出入口边界条件和固体管壁的约束条件密切相关。管壁的约束会引起气泡振动时出现强烈的非对称效应,并导致内壁压力峰值显著增加,而这些在用Rayleigh-Plesset方程计算时被明显忽略和低估了。
(3)建立了真实血管约束下的气泡-血液-管壁三相耦联动力学模型。考虑了管壁的惯性效应和柔性影响。计算结果表明,管壁越薄、环向刚度越大、初始血压越高,则气泡的非对称效应越强,管壁内的应力波动幅度也越大。因此老人、儿童和某些疾病病人(心血管病人、糖尿病人等)在超声波辅助治疗时危险性更高。
(4)研究了血液粘性对约束气泡振动的影响,证明了气泡的非对称振动模态是造成管壁损伤的主要原因,并且发现沿环向撕裂是其主要破坏形式。
(5)提出了双层微血管约束下的气泡动力学模型,并据此分析了气泡的非对称振动特征和壳壁应力的变化规律。计算发现,在气泡-血管耦合振动过程中,当内层壳的刚度增加时,尽管气泡的非对称振动效应以及流体对管壁的冲击幅度都变化不大,但是内膜层的环向应力却急剧增加。这一结果说明,血管硬化病人,在超声波碎石等治疗中,比正常人存在更大的风险。
本文系统地建立了伪弹性微管约束下的气-液-固耦联动力学模型,深入研究了气泡的非对称振动特征、血液的粘性效应、管壁材料的性质以及尺寸等对管壁应力和变形的影响规律,证明了气泡的非对称振动模态是造成管壁损伤的主要原因,发现了沿环向撕裂是其主要的破坏形式。这些对于设计有效的预防措施,安全使用超声碎石技术和定点送药技术等具有非常重要的理论意义和应用价值。
Medical bubbles have been widely applied in ultrasonic imaging (UI), targeted drug delivery (TDD) and shock wave lithotripsy (SWL). But for subgroup patients in these treatments, the injuries of renal tissue and vascular system are caused by bubbles oscillating and rupturing. Therefore, it has theoretical and clinical importance to explore the constraint oscillation mechanicsm of medical microbubbles. In this dissertation, by using the principle of liquid-solid coupled vibration and the method of computational fluid dynamics, the non-spherical oscillation characteristics of a medical microbubble and the corresponding dynamic responses of a micro blood vessel are investigated. Specific innovative contents are as follows:
(1) Double-layered structural theory of the ultrasound contrast agent (UCA) and its analysis method are introduced. To obtain excellent scattering ratio and sufficient reliability in UCA, we propose a new double-layered spherical shell structure and obtain the relationship between reflectivity and frequency. We also calculate and analyze the effects of thickness, material coefficients and viscoelastic damping of outer shell on the scattering characteristics of the structure. The results show scattering features of the double-layered shell are remarkably improved by an appropriate soft outer shell in UI.
(2) We present an ellipsoidal evolving model of constrained bubble according to the experimental observation in vivo, and construct an asysmmetric oscillation theory to analyze a non-spherical bubble. Computational results show that oscillating bubble profile depends on the liquid and solid boundary conditions, and indicate that the asymmetric effects of bubble oscillation due to the vessel constraint lead to a larger pressure exerted on the vessel, which is obviously underestimated or ignored by the Rayleigh–Plesset equation.
(3) We propose a three-phase dynamic model of a bubble-blood-vessel coupled oscillation system with a real constraint blood vessel. Inertial effect and compliance effect of the microvessel are taken into account. Calculated results show that a vessel wall with the thinner vessel or larger circumferential stiffness or higher pre-existing blood pressure correspond to the stronger bubble asymmetric measure and larger vessel stress amplitude. Thus elders, children and some special subjects such as cardiovascular and diabete patients, are higher risk in assisted therapy involving shock waves.
(4) The blood viscosity effects in course of constrained bubble oscillating are investigated. It has been proved that asymmetrical oscillation mode is a primary factor for vascular injury and circumferentially tearing is the dominant rupture mode.
(5) A new dynamic model about a bubble confined inside a double-layer micovessel is proposed, and then the asymmetric oscillation characterists of the microbubble and the regarding stress changes of the vessel are analyzed. It exhibits inconspicuous fluctuation with the asymmetrical scale of bubble oscillation and the liquid pressure exerted on the vessel wall, however, the corresponding dynamic circumferential stress of inner intima layer is increasing acutely. These conclusions indicate that the atherosclerotic patients have a higher risk in SWL.
We systematically propose and develop a bubble-liquid-vessel dynamic coupled model about constrained microbubble oscillation inside a micro pseudoelastic blood vessel, and investigate various effects on stresses and deformation of a vessel wall including asymmetric bubble oscillation, blood viscocity and vessel material and geometric papameters. We also prove that asymmetrical oscillation is a primary factor for vascular injury and circumferentially tearing is the dominant rupture mode. These conclusions have significant theory and application importances in safety of TDD and SWL.
引文
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