An inelastic multi-mechanism constitutive equation for cerebral arterial tissue

Intracranial aneurysms (ICA) are abnormal saccular dilations of cerebral arteries, commonly found at apices of arterial bifurcations and outer walls of curved arterial segments. Histological evidence suggests the stages in ICA development include the deformation of a segment of arterial wall into a “bleb” with no identifiable neck region followed by the development of an aneurysm with a clear neck. Afterwards, the aneurysm may undergo further enlargement, possibly with significant biological response including calcification and thrombosis. Past studies of the biomechanics of cerebral aneurysm tissue have been directed at modeling elastic deformations of pre-existing aneurysms. Taking this approach, the aneurysm wall is treated as a different entity than the arterial tissue from which it developed. In the current work, a nonlinear, inelastic, dual-mechanism constitutive equation for cerebral arterial tissue is developed. It is the first to model the recruitment of collagen fibers and degradation of the internal elastic lamina, two important characteristics of early stage aneurysm formation.     

Mechanical instability of normal and aneurysmal arteries

Tortuous arteries associated with aneurysms have been observed in aged patients with atherosclerosis and hypertension. However, the underlying mechanism is poorly understood. The objective of this study was to determine the effect of aneurysms on arterial buckling instability and the effect of buckling on aneurysm wall stress. We investigated the mechanical buckling and post-buckling behavior of normal and aneurysmal carotid arteries and aorta’s using computational simulations and experimental measurements to elucidate the interrelationship between artery buckling and aneurysms. Buckling tests were done in porcine carotid arteries with small aneurysms created using elastase treatment. Parametric studies were done for model aneurysms with orthotropic nonlinear elastic walls using finite element simulations. Our results demonstrated that arteries buckled at a critical buckling pressure and the post-buckling deflection increased nonlinearly with increasing pressure. The presence of an aneurysm can reduce the critical buckling pressure of arteries, although the effect depends on the aneurysm’s dimensions. Buckled aneurysms demonstrated a higher peak wall stress compared to unbuckled aneurysms under the same lumen pressure. We conclude that aneurysmal arteries are vulnerable to mechanical buckling and mechanical buckling could lead to high stresses in the aneurysm wall. Buckling could be a possible mechanism for the development of tortuous aneurysmal arteries such as in the Loeys–Dietz syndrome.     

Modeling rupture of growing aneurysms

Growth and rupture of aneurysms are driven by micro-structural alterations of the arterial wall yet precise mechanisms underlying the process remain to be uncovered. In the present work we examine a scenario when the aneurysm evolution is dominated by turnover of collagen fibers. In the latter case it is natural to hypothesize that rupture of individual fibers (or their bonds) causes the overall aneurysm rupture. We examine this hypothesis in computer simulations of growing aneurysms in which constitutive equations describe both collagen evolution and failure. Failure is enforced in constitutive equations by limiting strain energy that can be accumulated in a fiber. Within the proposed theoretical framework we find a range of parameters that lead to the aneurysm rupture. We conclude in a qualitative agreement with clinical observations that some aneurysms will rupture while others will not.     

The detection of<Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> in aneurysm of abdominal aorta and in normal aortic wall of organ donors

Sixty patients underwent surgery due to abdominal aortic aneurysms; the group included 30 patients with asymptomatic aneurysm and 30 with ruptured aneurysm. A control group comprised 30 organ donors. Surgical specimens derived from aneurysm or aorta fragments were investigated for Chlamydia pneumoniae DNA using PCR. In asymptomatic aneurysms, DNA was found in 9 cases (29%), and in ruptured aneurysms in 14 cases (49%). In the control group, C. pneumoniae DNA was not detected in an aortic wall. These results suggest that healthy aortic wall is not susceptible to chlamydial infection. A large number of aneurysm infections implies C. pneumoniae role in proteolysis and degradation of the aneurysm wall. The biological effect of this process may cause an enlargement of the aneurysm.     

An Analysis of 1256 Cases of Sporadic Ruptured Cerebral Aneurysm in a Single Chinese Institution

Background

To review the epidemiology of sporadic ruptured cerebral aneurysm.

Methods

This is a retrospective study of consecutive 1256 Chinese patients between January 2006 and January 2013, who were admitted to the Second Hospital of Hebei Medical University, China, for spontaneous subarachnoid hemorrhage due to a rupture of cerebral artery aneurysm. In 288 males and 478 females, the size of aneurysms was measured by a neuroradiologist on DSA. In 123 males and 184 females, the size of the ruptured aneurysms was not measured. The remaining patients, with 61 males and 122 females, had multiple aneurysms, and the medical record could not reliably determine the specific aneurysm responsible for the rupture.

Results

In total there were 784 females and 472 males with a female/male ratio of 1.66. The female/male ratio was down to 0.50 for patients younger than 35 yrs. For both males and females, aneurysm rupture was most common during the age of 50–59 yrs. Ruptured aneurysms were mostly of 2 mm–5 mm in size (47.1%), followed by 5 mm–10 mm (39.7%). Ruptured single cerebral aneurysm occurred in anterior circulation in 95.0% of the cases, with 5.0% occurred in posterior circulation. Ruptured aneurysm most commonly occurred at posterior communicating artery (34.9%) and anterior communicating artery (29.5%). 183 cases (14.6%) had multiple aneurysms.

Conclusions

With younger patients, there is a male predominance in our series. Ninety percent of patients have ruptured aneurysms less than 10 mm in size.     

Morphological Parameters Associated with Ruptured Posterior Communicating Aneurysms

The rupture risk of unruptured intracranial aneurysms is known to be dependent on the size of the aneurysm. However, the association of morphological characteristics with ruptured aneurysms has not been established in a systematic and location specific manner for the most common aneurysm locations. We evaluated posterior communicating artery (PCoA) aneurysms for morphological parameters associated with aneurysm rupture in that location. CT angiograms were evaluated to generate 3-D models of the aneurysms and surrounding vasculature. Univariate and multivariate analyses were performed to evaluate morphological parameters including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation, aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From 2005–2012, 148 PCoA aneurysms were treated in a single institution. Preoperative CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed. Multivariate logistic regression revealed that smaller volume (p = 0.011), larger aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance (p = 0.005) were the most strongly associated with aneurysm rupture after adjusting for all other clinical and morphological variables. Multivariate subgroup analysis for patients with visualized PCoA demonstrated that larger neck diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011) were significantly associated with rupture. Intracerebral hemorrhage was associated with smaller volume, larger maximum height, and smaller aneurysm angle, in addition to lateral projection, male sex, and lack of hypertension. We found that shorter ICA bifurcation to aneurysm distance is significantly associated with PCoA aneurysm rupture. This is a new physically intuitive parameter that can be measured easily and therefore be readily applied in clinical practice to aid in the evaluation of patients with PCoA aneurysms.     

Reduced M2 macrophages and adventitia collagen dampen the structural integrity of blood blister–like aneurysms and induce preoperative rerupture

ObjectiveBlood blister–like aneurysms (BBAs) are extremely rare aneurysms. They are predisposed to preoperative rerupture with a high case‐fatality rate. Here, we attempt to interrogate the distinct clinicopathology and the histological basis underlying its clinical rerupture.MethodsThree middle meningeal arteries, 11 BBA (5 reruptured, 6 non‐rerupture) and 19 saccular aneurysm samples were obtained for histopathological investigation. Three reruptured BBAs, 3 non‐reruptured BBAs and 6 saccular (3 ruptured, 3 unruptured) aneurysms were obtained for quantitative flow cytometry analysis.ResultsCompared with true saccular aneurysms, the BBA aneurysm wall lacks arterial stroma cells including CD31+ endothelial cells and α‐SMA + smooth muscle cells. Only fibroblasts and adventitial collagen were observed in the BBA aneurysm wall. Meanwhile, BBAs were enriched with infiltrated inflammatory cells, especially polarized macrophages. Based on the rerupture status, those reruptured BBAs showed drastically reduced fibroblasts and adventitia collagen. Moreover, M2‐polarized macrophages were observed dominant in BBAs and exhibit repairing cellular functions based on their interplays with arterial fibroblasts. Reduced M2 macrophages and arterial tissue repairing modulation may be responsible for the decreasing collagen synthesis and fibrosis repairment, which potentially dampens the aneurysm integrity and induces BBA aneurysm reruputre.ConclusionsBBAs poses histopathological features of occult pseudoaneurysms or dissecting aneurysms. Reduced M2 macrophages and adventitia collagen may dampen the structural integrity of BBAs and induce preoperative rerupture.     

Early and late results of resection of abdominal aortic aneurysms.

Resection of the abdominal aortic aneurysm is being performed with decreasing operative mortality and morbidity. Among 190 patients undergoing this procedure at the Ottawa Civic Hospital between 1970 and 1975, 53 (28%) had a ruptured aneurysm and 137 (72%), a nonruptured aneurysm. Mean age of the patients was 66.2 years. Concomitant disease was frequent, 73% of patients having two or more associated diseases; the average number of associated diseases per patient was 2.25. Operative mortality in the group with ruptured aneurysms was 51%, and in the group with nonruptured aneurysms, 4%. Postoperative morbidity was 85% among those with a ruptured aneurysm, 67% among those with imminent rupture before operation and 34% among the others with a nonruptured aneurysm. Graft complications occurred in 15% of those with a ruptured aneurysm and 9% of those with a nonruptured aneurysm. Among survivors of the operation 73% and 81% of those with a ruptured and a nonruptured aneurysm, respectively, are known to be alive. In both groups causes of late death included infection or thrombosis of the graft and mesenteric thrombosis, as well as causes unrelated to the operation. Surgical management of the abdominal aortic aneurysm is advocated in all but patients at poor risk for operation who have asymptomatic aneurysms less than 6 cm in diameter.     

Intravascular embolization of cerebral aneurysms by mechanically detachable micro-spirals

The paper presents experience in embolizing arterial aneurysm, which of great value for interventional radiology. Endovascular embolization is a low-traumatic intervention, which reduces the time of rehabilitation in a patient and makes him active much earlier. The paper uses a sufficient body of data to provide evidence for the efficiency and safety of this technique in the treatment of aneurysms. The authors' experience allows one to expand indications for endovascular treatment of arterial aneurysm and to create a mechanism of embolization in practice, by applying the mechanically detachable spirals.     

Dynamic effects on the formation and rupture of aneurysms

Dynamic analysis of an axially stretched arterial wall with collagen fibers distributed in two preferred directions under a suddenly applied constant internal pressure along with the possibility of the formation and rupture of aneurysm are examined within the framework of nonlinear dynamics. A two layer tube model with the fiber-reinforced composite-based incompressible anisotropic hyper-elastic material is employed to model the mechanical behavior of the arterial wall. The maximum amplitudes and the phase diagrams are given by numerical computation of the differential relation. It is shown that the arterial wall undergoes nonlinear periodic oscillation and no aneurysms are formed under the normal condition. However, an aneurysm may be formed under such abnormal conditions as the stiffness of the fibers is deduced or the direction of the fibers is oriented towards the axial direction. Furthermore, the possibility for the rupture of aneurysm is discussed with the distribution of stresses.     

Posterior Cerebral Artery Angle and the Rupture of Basilar Tip Aneurysms

Since the initial publication of the International Study of Unruptured Intracranial Aneurysms (ISUIA), management of unruptured intracranial aneurysms has been mainly based on the size of the aneurysm. The contribution of morphological characteristics to treatment decisions of unruptured aneurysms has not been well studied in a systematic and location specific manner. We present a large sample of basilar artery tip aneurysms (BTA) that were assessed using a diverse array of morphological variables to determine the parameters associated with ruptured aneurysms. Demographic and clinical risk factors of aneurysm rupture were obtained from chart review. CT angiograms (CTA) were evaluated with Slicer, an open source visualization and image analysis software, to generate 3-D models of the aneurysms and surrounding vascular architecture. Morphological parameters examined in each model included aneurysm volume, aspect ratio, size ratio, aneurysm angle, basilar vessel angle, basilar flow angle, and vessel to vessel angles. Univariate and multivariate analyses were performed to determine statistical significance. From 2008–2013, 54 patients with BTA aneurysms were evaluated in a single institution, and CTAs from 33 patients (15 ruptured, 18 unruptured) were available and analyzed. Aneurysms that underwent reoperation, that were associated with arteriovenous malformations, or that lacked preoperative CTA were excluded. Multivariate logistic regression revealed that a larger angle between the posterior cerebral arteries (P1-P1 angle, p = 0.037) was most strongly associated with aneurysm rupture after adjusting for other morphological variables. In this location specific study of BTA aneurysms, the larger the angle formed between posterior cerebral arteries was found to be a new morphological parameter significantly associated with ruptured BTA aneurysms. This is a physically intuitive parameter that can be measured easily and readily applied in the clinical setting.     

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。     

T lymphocytes and aortic aneurysms

Aortic aneurysms are common and life threatening problems with high rates of death. The initiation and progression of aneurysms are characterized by extensive extracellular matrix degradation and immune cells invasion within arterial wall. During the pathogenesis of all aneurysms, inflammation and immune cells play a significant role. Although T cells are abundant in aneurysm tissue, their functions in initiation and propagation of aneurysms remain unclear. This review summarizes the current state of knowledge of T lymphocytes on this disease and focuses on potential mechanisms of specific T cell responses.     

Elevated levels of matrix metalloprotein-3 in patients with coronary aneurysm: A case control study

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of arterial aneurysms through increased proteolysis of extracellular matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme activity in the arterial wall may act as a susceptibility factor for the development of coronary aneurysms. The aim of this study was to investigate the association between MMPs and presence of coronary aneurysms. METHODS: Thirty patients with aneurysmal coronary artery disease and stable angina were enrolled into study (Group 1). Fourteen coronary artery disease patients with stable angina were selected as control group (Group 2). MMP-1, MMP-3 and C-reactive protein (CRP) were measured in peripheral venous blood and matched between the groups. RESULTS: Serum MMP-3 level was higher in patients with aneurismal coronary artery disease compared to the control group (20.23 +/- 14.68 vs 11.45 +/- 6.55 ng/ml, p = 0.039). Serum MMP-1 (13.63 +/- 7.73 vs 12.15 +/- 6.27 ng/ml, p = 0.52) and CRP levels (4.78 +/- 1.47 vs 4.05 +/- 1.53 mg/l, p = 0.13) were not significantly different between the groups. CONCLUSION: MMPs can cause arterial wall destruction. MMP-3 may play role in the pathogenesis of coronary aneurysm development through increased proteolysis of extracellular matrix proteins.     

Extracellular Matrix Defects in Aneurysmal Fibulin-4 Mice Predispose to Lung Emphysema

Background

In this study we set out to investigate the clinically observed relationship between chronic obstructive pulmonary disease (COPD) and aortic aneurysms. We tested the hypothesis that an inherited deficiency of connective tissue might play a role in the combined development of pulmonary emphysema and vascular disease.

Methods

We first determined the prevalence of chronic obstructive pulmonary disease in a clinical cohort of aortic aneurysms patients and arterial occlusive disease patients. Subsequently, we used a combined approach comprising pathological, functional, molecular imaging, immunological and gene expression analysis to reveal the sequence of events that culminates in pulmonary emphysema in aneurysmal Fibulin-4 deficient (Fibulin-4^R) mice.

Results

Here we show that COPD is significantly more prevalent in aneurysm patients compared to arterial occlusive disease patients, independent of smoking, other clinical risk factors and inflammation. In addition, we demonstrate that aneurysmal Fibulin-4^R/R mice display severe developmental lung emphysema, whereas Fibulin-4^+/R mice acquire alveolar breakdown with age and upon infectious stress. This vicious circle is further exacerbated by the diminished antiprotease capacity of the lungs and ultimately results in the development of pulmonary emphysema.

Conclusions

Our experimental data identify genetic susceptibility to extracellular matrix degradation and secondary inflammation as the common mechanisms in both COPD and aneurysm formation.     

Survivors of ruptured abdominal aortic aneurysm: the iceberg's tip.

In four and a half years 25 patients in one community suffered a ruptured abdominal aortic aneurysm. Eleven died at home, nine died without operation in hospital, and only five had the aneurysm removed. There were four survivors. A further seven patients might have lived had they had a prompt operation. The average operative mortality for ruptured aneurysms among series reported in British journals is 53%, but the survivors are a small minority of the total number of people in the community whose aneurysms rupture. No basis could be found for the view that replacing an aortic aneurysm with a straight graft (while leaving behind aneurysmal common iliac arteries) lowers the operative mortality. On the contrary, oversimplifying the operation may be hazardous.     

64层螺旋CT脑血管造影在颅内动脉瘤诊断中的应用

目的:探讨64层螺旋CT血管造影(CTA)对颅内动脉瘤的诊断价值。方法:回顾性分析54例临床怀疑为颅内动脉瘤,并同时行64层CTA和DSA检查的病例,其中47例疑诊动脉瘤患者行动脉瘤夹闭手术,将MSCTA,DSA与手术结果对照。结果:54患者中经MSCTA检出57个动脉瘤,DSA检出55个动脉瘤,另7例MSCTA和DSA均未检出动脉瘤,余47例接受手术并检出58个动脉瘤。64层CTA发现动脉瘤的敏感性为96.6%,特异性为87.5%,准确性为96.5%,阳性预测值为98.2,阴性预测值为77.7。MIP和VR技术对动脉瘤的形态、分支血管、血栓和钙化方面的显示优于DSA。结论:64层CTA诊断颅内动脉瘤具有较好的异性、敏感性及三维显示能力,具有较高的临床应用价值。。     

Fluid–structure interaction (FSI) simulation for studying the impact of atherosclerosis on hemodynamics,arterial tissue remodeling,and initiation risk of intracranial aneurysms

The biomechanical and hemodynamic effects of atherosclerosis on the initiation of intracranial aneurysms (IA) are not yet clearly discovered. Also, studies for the observation of hemodynamic variation due to atherosclerotic stenosis and its impact on arterial remodeling and aneurysm genesis remain a controversial field of vascular engineering. The majority of studies performed are relevant to computational fluid dynamic (CFD) simulations. CFD studies are limited in consideration of blood and arterial tissue interactions. In this work, the interaction of the blood and vessel tissue because of atherosclerotic occlusions is studied by developing a fluid and structure interaction (FSI) analysis for the first time. The FSI presents a semi-realistic simulation environment to observe how the blood and vessels' structural interactions can increase the accuracy of the biomechanical study results. In the first step, many different intracranial vessels are modeled for an investigation of the biomechanical and hemodynamic effects of atherosclerosis in arterial tissue remodeling. Three physiological conditions of an intact artery, the artery with intracranial atherosclerosis (ICAS), and an atherosclerotic aneurysm (ACA) are employed in the models with required assumptions. Finally, the obtained outputs are studied with comparative and statistical analyses according to the intact model in a normal physiological condition. The results show that existing occlusions in the cross-sectional area of the arteries play a determinative role in changing the hemodynamic behavior of the arterial segments. The undesirable variations in blood velocity and pressure throughout the vessels increase the risk of arterial tissue remodeling and aneurysm formation.

     

Analysis of Morphological Parameters to Differentiate Rupture Status in Anterior Communicating Artery Aneurysms

In contrast to size, the association of morphological characteristics of intracranial aneurysms with rupture has not been established in a systematic manner. We present an analysis of the morphological variables that are associated with rupture in anterior communicating artery aneurysms to determine site-specific risk variables. One hundred and twenty-four anterior communicating artery aneurysms were treated in a single institution from 2005 to 2010, and CT angiograms (CTAs) or rotational angiography from 79 patients (42 ruptured, 37 unruptured) were analyzed. Vascular imaging was evaluated with 3D Slicer© to generate models of the aneurysms and surrounding vasculature. Morphological parameters were examined using univariate and multivariate analysis and included aneurysm volume, aspect ratio, size ratio, distance to bifurcation, aneurysm angle, vessel angle, flow angle, and parent-daughter angle. Multivariate logistic regression revealed that size ratio, flow angle, and parent-daughter angle were associated with aneurysm rupture after adjustment for age, sex, smoking history, and other clinical risk factors. Simple morphological parameters such as size ratio, flow angle, and parent-daughter angle may thus aid in the evaluation of rupture risk of anterior communicating artery 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.