一类新Willis环脑动脉瘤系统的构造及最优控制

本文基于6-氨基乙酸减小血流速度及缓冲血流波动的性质,在6-氨基乙酸的作用下,构建了一个新的脑动脉瘤数学模型.该模型很好地体现了6-氨基乙酸、血流速度及血流速度变化率三者之间的相互作用关系.鉴于脑动脉瘤的医疗费用颇高及破裂后的死亡率较高,从而有必要从数学的角度研究该模型的最优控制,以致在一定条件下花费最小且医疗效果最佳.本文首先证明了该模型最优控制的存在性;其次通过构造Lagrangian函数及运用最大值原理,证明了最优控制的唯一性.从理论上得到Willis环脑动脉瘤内血流波动最小的条件,这为预防脑动脉瘤的破裂提供了理论依据..     

颈动脉瘤个体化模型血流数值分析

动脉瘤日益受到广泛关注,介入术成为动脉瘤的理想化治疗方法,但现实临床实践缺少理论支撑,所以数值模拟成为研究动脉瘤血流动力学参数的关键技术。为了研究动脉瘤的血液动力特性,进而探讨不同参数对动脉瘤的血液动力学特性影响因素,本研究基于1例个体化动脉瘤的影像数据,通过影像提取的方法建立了个体化动脉瘤模型,并根据双向流固耦合的方法进行血流场分析(流线,壁面变形分布,壁面剪切力分布)。通过数值分析结果表明,在一个心动周期的不同时刻动脉瘤瘤腔内的涡流强度先增强再减弱并在0.1 s达到最强。动脉瘤壁面的壁面切应力(wall shear stress, WSS)的分布也随着时间的变化,同样在0.1 s时刻壁面WSS分布梯度较大,到0.22 s时刻以及后各个时刻达到均匀无梯度分布。而从壁面变形来看,一个心动周期前0.3 s时刻动脉瘤壁的最大变形位置均为瘤顶处并呈现由小到大再到小的变化(0.1 s时刻达到最大变形量),0.3 s时刻的最大变形量位置发生改变,为瘤颈中间部位,但变形量很小为0.01 mm。     

不同造影方法显示弹性酶诱导的兔囊状动脉瘤

目的评估经股动脉穿刺超选造影、静脉造影、心脏穿刺造影和左侧耳中央动脉穿刺造影方法显示弹性酶诱导的兔囊状动脉瘤的可行性。方法取10只新西兰兔,采用弹性酶诱导方法制作兔右侧颈总动脉起始部囊状动脉瘤模型。术后3周对所有动物分别进行经股动脉穿刺超选造影、静脉造影、心脏穿刺造影和左侧耳中央动脉穿刺造影,根据造影结果测量动脉瘤短径、长径和瘤颈宽。采用重复测量设计的方差分析方法比较不同造影方法显示的动脉瘤相关参数测量结果差异。结果采用经股动脉穿刺超选造影、静脉造影、心脏穿刺造影和左侧耳中央动脉穿刺造影方法均能较清楚的显示的动脉瘤,比较不同造影方法测量的动脉瘤短径、长径和瘤颈宽均无统计学差异（P值分别是0.646,0.427和0.625）。结论不同的造影方法均能较准确显示弹性酶诱导的兔囊状动脉瘤大小,根据不同的实验目的和条件可选用不同的造影方法。     

两种败血症休克模型大鼠心肌细胞一氧化氮合酶活性的改变

目的：观察两种败血症休克模型大鼠的血流动力学及心肌细胞一氧化氮合酶活性变化的异同,探讨一氧化氮合酶参与败血症休克性心肌抑制的机制。方法：采用注射脂多糖（LPS）诱导及盲肠结扎穿孔（CLP）致腹膜炎诱导败血症休克模型,测定血流动力学指标以及心肌细胞胞浆一氧化氮合酶（NOS）活性。结果：①CLP模型大鼠的血流动力学指标随时间呈先上升后下降的趋势,LPS模型直接表现为类似于CLP模型晚期的动力学状态。在使用NOS抑制剂N-硝基-L精氨酸甲酯（L-NAME）后,CLP模型晚期及LPS模型的心室动力学指标均有明显改善。②CLP模型大鼠心肌细胞胞浆NOS活性在败血症中期达到最大。与假手术组相比,LPS模型、CLP模型晚期心肌细胞胞浆NOS活性均有明显增加,但是LPS模型与CLP模型晚期两组之间无明显差异。③使用L-NAME后,CLP晚期组与LPS组亚硝基及硝基化合物生成量均明显降低（P〈0.01）。其中,LPS组与CLP晚期组相比,前者固定表达型NOS生成亚硝基及硝基化合物生成量明显高于后者（P〈0．01）。结论：在LPS与CLP诱导的败血症休克模型中,心肌NOS是引起心室动力学变化的主要因素;在两种模型,心肌NOS亚型的表达不同,在LPS模型中主要为iNOS,而在CLP模型中则可能是cNOS和iNOS共同发挥作用。     

彩色双功能超声在诊断肢体假性动脉瘤中应用价值(附16例分析)

目的评价彩色双功能超声在检查创伤性肢体假性动脉瘤中的诊断价值。方法利用高频线阵探头对16例(17个)肢体假性动脉瘤患者进行检查,并与血管造影进行对比分析。结果16例肢体假性动脉瘤首先经超声检查诊断,所有病例假性动脉瘤体内均有红蓝相间的“来和去”特征性彩色血流图像,6例行血管造影检查,结果与超声诊断完全相符。诊断符合率为100%。11例手术切除,其中10例与超声检查结果相符,1例合并桡动脉漏超声未能检出。超声诊断符合率为92%。结论彩色多普勒超声诊断创伤性肢体假性动脉瘤在临床上具有重要的诊断价值。     

以CT图像为基础的冠状动脉狭窄处血流动力学研究

目的:冠状动脉粥样硬化好发于具有特殊几何构型的血管部位,提示血流动力学参数在粥样硬化形成方面起到重要作用.以往研究多局限于理想的血管模型,本文旨在探索以CT图像为基础构建个体化冠状动脉血流动力学模型的技术方法,对人体左冠状动脉前降支粥样硬化病变狭窄处进行计算流体动力学(computational fluid dynamics,CFD)数值模拟,探讨冠状动脉粥样硬化病变形成和发展的血流动力学机制.方法:用MIMICS软件读取CTA数据,以CT图像为基础进行冠状动脉三维几何建模,假设动脉血流为层流、不可压缩、牛顿流体,入口血液流速随时间周期性变化,应用有限体积法FLUENT软件进行血流数值模拟,分析与动脉粥样硬化形成、发展相关的血流动力学参数.结果:获得个体化左冠状动脉前降支狭窄处血管模型及血流动力学参数,数值模拟结果包括冠状动脉的血液流场、壁面压力(wall pressure WP)及壁面切应力(wall shear stress WSS)分布,可见狭窄段血管血液流速加快,WP降低、WSS增高,且在狭窄邻近区域出现低WSS区、较高的WP及血液湍流区域.结论:以CT图像为基础的CFD技术是在体评价人狭窄冠状动脉内血流动力学状况与冠状动脉粥样硬化病变之间关系的有效方法,能够更为真实的建立人体血管几何模型,为分析血流动力学参数与冠状动脉粥样硬化形成与发展的关系提供研究手段.     

腹主动脉瘤的流固耦合分析方法研究

目的:将流固耦合分析方法运用于血流动力学的研究,可以获得更加准确的结果,为临床诊断和治疗提供有效的指导.方法:本文运用ANSYS和CFX对腹主动脉瘤(Abdominal Aortic Aneurysm,AAA)进行流固耦合模拟分析,以便获得动脉瘤的血流速度和瘤壁的应力分布,判断易破裂危险区域.结果:实验结果表明,本例的腹部主动脉瘤应力峰值位于瘤体颈部.结论:流动和壁面切应力分布揭示动脉瘤颈部为破裂的危险区域.     

椎动脉狭窄内血液两相流动数值模拟分析

目的:对应用三维重构得到的人体真实椎动脉进行血液两相流数值模拟,与经典单相流牛顿血液模型对比,分析动脉粥样硬化等病因与椎动脉狭窄处的血流动力学关系。方法:把考虑血细胞和血浆的两相流血液模型应用到逆向工程方法构建的基于人体生理解剖特征的椎动脉三维几何模型中去进行数值模拟,分析血细胞分布情况等血流动力学参数,并与单相流模型的模拟结果进行对比。结果:通过瞬态模拟计算,得到了椎动脉在心动周期内不同时刻的两相流和单相流模型的血流动力学参数。结论:通过对比单相流数值模拟结果,得出血管狭窄处血细胞出现聚集,血流更加复杂和低壁面切应力分布等与动脉粥样硬化及血栓的形成相关的结论。并且与两相流模型相比,单相流模型存在如无法获得如血细胞分布等不足,为进一步深入研究椎动脉等疾病的发病机理提供方法和理论支持。     

埃他卡林对压力超负荷大鼠心室重构和血浆中PGI2的影响

目的：观察埃他卡林（IPT）对压力超负荷大鼠心室重构的影响,探讨其保护作用与血浆中前列环素（PGI2）的关系。方法：SD大鼠经腹主动脉缩窄6周后诱导压力超负荷高血压模型,随机分为5组（n=9）：①假手术组;②模型组;③IPT 3mg／kg组（IPT 3）;④吲哚美辛2mg/kg（Indo2）组;⑤IPT 3mg／kg＋吲哚美辛2mg／kg（IPT 3＋Indo2）组。RM-6000八导生理记录仪记录血流动力学改变,称量计算心脏重量指数,HE染色和iassort’s染色观察心肌组织病理学改变,比色法检测心肌组织羟脯氨酸含量,放免法检测血浆中PGI2含量。结果：腹主动脉缩窄6周后,与假手术组相比,模型组大鼠出现了明显的高血流动力学状态和心室重构,血浆中PGI2含量也明显降低。而IPT 3mg／kg实验治疗6周可明显改善上述变化。单用吲哚美辛可进一步恶化大鼠的高血流动力学状态和心室重构,合用肼可明显改善高血流动力学状态和心肌纤维化,明显抑制血浆中PGI2含量的降低。结论：IPT可明显逆转腹主动脉缩窄／压力超负荷大鼠的心室重构,其机制可能与胛作用于内皮细胞上的KATP通道,恢复内皮细胞的分泌功能增加PGI2的合成和分泌密切相关。     

手术前后三维动脉瘤模型的血液动力学模拟对比

本研究目的在于从临床患者的医学影像出发,在手术前后分别对三维动脉瘤模型进行了定常模拟,观察动脉瘤模型内的流场形态以及各血液动力学参数的变化并进行讨论。由于三维的数值模拟比二维的跟接近实际,而且更加直观形象,所以研究结果对于分析动脉瘤的破裂机理具有重要的临床应用价值。     

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms.Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions.The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat''s descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta.We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat.     

Estimation of aneurysm wall stresses created by treatment with a shape memory polymer foam device

In this study, compliant latex thin-walled aneurysm models are fabricated to investigate the effects of expansion of shape memory polymer foam. A simplified cylindrical model is selected for the in-vitro aneurysm, which is a simplification of a real, saccular aneurysm. The studies are performed by crimping shape memory polymer foams, originally 6 and 8 mm in diameter, and monitoring the resulting deformation when deployed into 4-mm-diameter thin-walled latex tubes. The deformations of the latex tubes are used as inputs to physical, analytical, and computational models to estimate the circumferential stresses. Using the results of the stress analysis in the latex aneurysm model, a computational model of the human aneurysm is developed by changing the geometry and material properties. The model is then used to predict the stresses that would develop in a human aneurysm. The experimental, simulation, and analytical results suggest that shape memory polymer foams have potential of being a safe treatment for intracranial saccular aneurysms. In particular, this work suggests oversized shape memory foams may be used to better fill the entire aneurysm cavity while generating stresses below the aneurysm wall breaking stresses.     

Can aspect ratio be used to categorize intra-aneurysmal hemodynamics?-A study of elastase induced aneurysms in rabbit

Clinical studies suggest that aneurysm aspect ratio (AR) is an important indicator of rupture likelihood. The importance of AR is hypothesized to arise from its influence on intra-aneurysmal hemodynamics. It has been conjectured that slower flow in high AR sacs leads to a cascade of biological activities that weaken the aneurysm wall (Ujiie et al.,1999). However, the connection between AR, hemodynamics and wall weakening has never been proven. Animal models of saccular aneurysms provide a venue for evaluating this conjecture. The focus of this work was to evaluate whether a commonly used elastase induced aneurysm model in rabbits is suitable for a study of this kind from a hemodynamic perspective. In particular, to assess whether hemodynamic factors in low and high AR sacs are statistically different. To achieve this objective, saccular aneurysms were created in 51 rabbits and pulsatile computational fluid dynamics (CFD) studies were performed using rabbit specific inflows. Distinct hemodynamics were found in the low AR (AR<1.8, n=25), and high AR (AR>2.2, n=18) models. A single, stable recirculation zone was present in all low AR aneurysms, whereas a second, transient recirculation zone was also found in the superior aspect of the aneurysm dome for all high AR cases. Aneurysms with AR between 1.8 and 2.2 displayed transitional flow patterns. Differences in values and distributions of hemodynamic parameters were found between low and high AR cases including time averaged wall shear stress, oscillatory shear index, relative residence time and non-dimensional inflow rate. This work lays the foundation for future studies of the dependence of growth and remodeling on AR in the rabbit model and provides a motivation for further studies of the coupling between AR and hemodynamics in human aneurysms.     

Further evidence for the dynamic stability of intracranial saccular aneurysms

It has long been thought that intracranial saccular aneurysms enlarge and rupture because of mechanical instabilities. Recent nonlinear analyses suggest, however, that at least certain sub-classes of aneurysms do not exhibit quasi-static limit point instabilities or dynamic instabilities in response to periodic loading, and consequently, that the natural history of these lesions is likely governed by growth and remodeling processes. In this paper, we present additional results that support the finding that one particular sub-class of saccular aneurysms is dynamically stable. Specifically, we extended recent results of Shah and Humphrey, which are based on the assumption that some saccular aneurysms can be modeled as spherical elastic membranes surrounded by a viscous cerebrospinal fluid, to account for a viscohyperelastic behavior of the aneurysm. It is shown that inclusion of a "short-term" viscoelastic contribution to the mechanical behavior of an aneurysm serves to increase its dynamic stability against various disturbances.     

Finite strain elastodynamics of intracranial saccular aneurysms.

Various investigators suggest that intracranial saccular aneurysms are dynamically unstable, that they resonate in response to pulsatile blood flow. This hypothesis is based on linearized analyses or experiments on rubber "models", however, and there is a need for a more critical examination. Toward this end, we (a) derive a new nonlinear equation of motion for a pulsating spherical aneurysm that is surrounded by cerebral spinal fluid and whose behavior is described by a Fung-type pseudostrain-energy function that fits data on human lesions, and (b) use methods of nonlinear dynamics to examine the stability of such lesions against perturbations to both in vivo and in vitro conditions. The numerical results suggest that this sub-class of lesions is dynamically stable. Moreover, with the exception of transients associated with initial perturbations, inertial effects appear to be insignificant for fundamental forcing frequencies less than 10 Hz and hence for typical physiologic and laboratory conditions. We submit, therefore, that further study of the mechanics of saccular aneurysms should be focused on quasi-static stress analyses that investigate the roles of lesion geometry and material properties, including growth and remodeling.     

Hemodynamic stress in lateral saccular aneurysms

The flow velocities in glass and silastic lateral aneurysm models were quantitatively measured with the non-invasive laser Doppler method. The influences of the elasticity of the wall, the pulse wave and the properties of the perfusion medium on the intra-aneurysmal circulation were investigated. As shown previously, the inflow into the aneurysm arose from the downstream lip and was directed toward the center of the fundus. Backflow to the parent vessel took place along the walls of the fundus. With non-pulsatile perfusion, flow velocities in the center of the standardized aneurysms varied between 0.4 and 2% of the maximum velocity in the parent vessel. With pulsatile perfusion, flow velocities in the center of the fundus ranged between 8 and 13% of the flow velocity in the axis of the parent vessel. Flow velocities in the aneurysms were slower with a polymer suspension with blood-like properties compared to a glycerol/water solution. Flow velocity measurements near the aneurysmal wall allowed the estimation of the shear stresses at critical locations. The maximum shear stresses at the downstream lip of the aneurysm were in the range of the stresses measured at the flow divider of an arterial bifurcation. The present results suggest that in human saccular aneurysms intra-aneurysmal flow and shear stress on the wall are directly related to the pulsatility of perfusion, i.e. the systolic/diastolic pressure difference and that the tendency to spontaneous thrombosis depends on the viscoelastic properties of the blood, namely the hematocrit.     

Kawasaki disease causing saccular aneurysms of the coronary arteries

A 22-year-old man was referred for treatment of a 45 mm saccular aneurysm of the right coronary artery (RCA) and a 15 mm saccular aneurysm of the left anterior descending artery (LAD). The patient developed Kawasaki disease in 1998. The aneurysms were diagnosed in 2002. The RCA showed thrombus formation. Until now the patient had remained asymptomatic. He now presented with effort angina. On coronary angiography and magnetic resonance imaging, an occluded aneurysm of the proximal RCA (45 mm) was seen with a second aneurysm more distally (22 mm).     

A theoretical model for fibroblast-controlled growth of saccular cerebral aneurysms

A new theoretical model for the growth of saccular cerebral aneurysms is proposed by extending the recent constitutive framework of Kroon and Holzapfel [2007a. A model for saccular cerebral aneurysm growth by collagen fibre remodelling. J. Theor. Biol. 247, 775-787]. The continuous turnover of collagen is taken to be the driving mechanism in aneurysmal growth. The collagen production rate depends on the magnitude of the cyclic deformation of fibroblasts, caused by the pulsating blood pressure during the cardiac cycle. The volume density of fibroblasts in the aneurysmal tissue is taken to be constant throughout the growth process. The growth model is assessed by considering the inflation of an axisymmetric membranous piece of aneurysmal tissue, with material characteristics representative of a cerebral aneurysm. The diastolic and systolic states of the aneurysm are computed, together with its load-free state. It turns out that the value of collagen pre-stretch, that determines growth speed and stability of the aneurysm, is of pivotal importance. The model is able to predict aneurysms with typical berry-like shapes observed clinically, and the predicted wall stresses correlate well with the experimentally obtained ultimate stresses of this type of tissue. The model predicts that aneurysms should fail when reaching a size of about 1.2-3.6 mm, which is smaller than what has been clinically observed. With some refinements, the model may, however, be used to predict future growth of diagnosed aneurysms.     

Computational haemodynamics in two idealised cerebral wide-necked aneurysms after stent placement

Endovascular stents are being commonly used to treat cerebral wide-necked aneurysms recently. The effect of a stent placed in the parent artery is not only to protect the parent artery from occlusion, due to extension of coils and thrombosis, but also to act as flow diverter to vary the haemodynamics in the aneurysm. In this article, two idealised cerebral wide-necked aneurysms were created, one was sidewall aneurysm with curved parent vessel and the other was terminal aneurysm with the bifurcated parent vessel. The plexiglass models of the two aneurysms were ‘treated’ with commercial porous intravascular stents. The stented physical models were scanned by Micro-CT and the numerical models of the two idealised cerebral wide-necked aneurysms after stent placement were constructed from the scanned image files. The pulsatile flow of non-Newtonian fluid inside the models was simulated by using computational fluid dynamics package. From the simulated flow dynamics, various haemodynamic characteristics such as velocity contours, wall shear stress and oscillatory shear index (OSI) were computed. The velocity of the jet entering the sacs reduced after stent was deployed across the necks of both sidewall and terminal aneurysms; the wall shear stress on the distal neck of sidewall aneurysm reduced, the wall shear stress on the dome of the terminal aneurysm increased and the OSI on the dome of the terminal aneurysm reduced. Therefore, stent placement not only promotes thrombus formation in both aneurysm models but also reduces the regrowth risk of the sidewall aneurysm and the rupture risk of the terminal aneurysm.