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1.
The abdominal aortic aneurysm (AAA) is a degenerating disease for which the end stage is the rupture of the vessel wall. Accurate prediction of the stresses acting on the aneurysm tissue may be used to determine the actual risk of rupture of a specific aneurysm. To accomplish this, a correct constitutive model for the aneurysmal aortic wall and any intraluminal thrombus (ILT) present within it are needed. Our laboratory has previously reported the mechanical properties of ILT. The aim of this work is to investigate the reliability of using population-mean values of ILT constitutive parameters to estimate AAA wall stress distribution. For this, a three-dimensional asymmetric model of an aneurysm including ILT was generated and a parametric study was conducted varying ILT constitutive properties within a physiological range. Results show that the presence of any ILT reduces and redistributes the stresses in the aortic wall markedly. Maximum variation in the peak wall stresses for all the models analyzed was 5%. Adopting a nonhomogeneous ILT did not alter the stress distribution. On the basis of these results, we infer that population mean parameters for ILT material characteristics can be used to reasonably estimate the wall stresses in patient specific aneurysm models. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Xx, 8710+e  相似文献   

2.
A novel computational particle-hemodynamics analysis of key criteria for the onset of an intraluminal thrombus (ILT) in a patient-specific abdominal aortic aneurysm (AAA) is presented. The focus is on enhanced platelet and white blood cell residence times as well as their elevated surface-shear loads in near-wall regions of the AAA sac. The generalized results support the hypothesis that a patient’s AAA geometry and associated particle-hemodynamics have the potential to entrap activated blood particles, which will play a role in the onset of ILT. Although the ILT history of only a single patient was considered, the modeling and simulation methodology provided allow for the development of an efficient computational tool to predict the onset of ILT formation in complex patient-specific cases.  相似文献   

3.
The optimum time to treat abdominal aortic aneurysms (AAAs) still remains an uncertain issue. The decision to intervene does not take in account the effects that wall curvature, intraluminal thrombus (ILT) properties and thickness have on rupture. The role of ILT in aneurysm dynamics and rupture has been controversial. In vitro testing of four silicone AAA models incorporating the ILT and aortic bifurcation was studied under physiological conditions. Pressures (P) and diameters (D) were analysed for models with and without ILT at different locations. The diametral strain, compliance and P/D curves were influenced by the presence, elastic stiffness and thickness of the ILT. In this case, the inclusion of ILT reduced the lumen area by 77% that resulted in a 0.5–81% reduction in compliance depending on ILT properties. With an increase in ILT stiffness from 0.05 to 0.2 MPa, the compliance was reduced by 81%. In the region of maximum diameter, there was a reduction of diametral strain and compliance except for the softer ILT which was more compliant throughout the proximal region. The shifting of the maximum diametral strain and compliance to the proximal neck was pronounced by an increase in ILT stiffness, thus creating a possible rupture site.  相似文献   

4.
The spatial distributions of both wall stress and wall strength are required to accurately evaluate the rupture potential for an individual abdominal aortic aneurysm (AAA). The purpose of this study was to develop a statistical model to non-invasively estimate the distribution of AAA wall strength. Seven parameters–namely age, gender, family history of AAA, smoking status, AAA size, local diameter, and local intraluminal thrombus (ILT) thickness–were either directly measured or recorded from the patients hospital chart. Wall strength values corresponding to these predictor variables were calculated from the tensile testing of surgically procured AAA wall specimens. Backwards–stepwise regression techniques were used to identify and eliminate insignificant predictors for wall strength. Linear mixed-effects modeling was used to derive a final statistical model for AAA wall strength, from which 95% confidence intervals on the model parameters were formed. The final statistical model for AAA wall strength consisted of the following variables: sex, family history, ILT thickness, and normalized transverse diameter. Demonstrative application of the model revealed a unique, complex wall strength distribution, with strength values ranging from 56 N/cm2 to 133 N/cm2. A four-parameter statistical model for the noninvasive estimation of patient-specific AAA wall strength distribution has been successfully developed. The currently developed model represents a first attempt towards the noninvasive assessment of AAA wall strength. Coupling this model with our stress analysis technique may provide a more accurate means to estimate patient-specific rupture potential of AAA.  相似文献   

5.
Human abdominal aortic aneurysm (AAA) expansion has been linked to the presence of a mural thrombus. Here we explored the mechanism of the continual luminal renewal of this thrombus and its ability to release biological markers potentially detectable in plasma. We also explored the ability of platelet inhibition to pacify the thrombus and to limit aneurysm progression in an experimental model. Blood samples and mural thrombi were collected in 20 AAA patients. In parallel, segments of sodium dodecyl sulfate-decellularized guinea pig aorta were xenografted onto the abdominal aorta of 30 rats to induce aneurysms. Fifteen rats received abciximab treatment and fifteen received irrelevant immunoglobulins. Procoagulant activity and platelet activation markers (microparticles, sP-selectin, sGPV, sCD40L) were increased threefold to fivefold in eluates from the luminal thrombus layer compared to other layers. All these markers were increased twofold to fivefold in patients' plasma compared to matched controls (P < 0.005). In the rat model, abciximab reduced both thrombus area and aneurysmal enlargement (P < 0.05). Platelet aggregation is probably responsible for the renewal of the thrombus in AAA. The luminal thrombus released markers of platelet activation that could easily be detected in plasma. Platelet inhibition limited aortic aneurysm expansion in a rat model, providing new therapeutic perspectives in the prevention of AAA enlargement.  相似文献   

6.
To explore possible mechanisms responsible for the absence of cell re-colonization of mural thrombi in aneurysms, we analyzed the release and storage of leukocyte proteases in the most luminal layer versus intermediate and abluminal layers of 10 mural thrombi of human abdominal aortic aneurysms. The luminal layer contained many polymorphonuclear leukocytes (PMNs), which released pro-matrix metalloproteinase (MMP)-9 and MMP-8. Leukocyte elastase was also stored and released by the luminal layer (immunohistochemistry, activity on synthetic substrates, and casein zymography). Acid buffer allowed extraction of leukocyte elastase from the luminal layer, which was inhibited by elastase inhibitors. Casein zymography of luminal extracts and conditioned medium from formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMNs exhibited a similar lysis pattern, corresponding to elastase activity. Smooth muscle cell (SMC) seeding resulted in colonization of the intermediate thrombus layer ex vivo but not of the luminal layer. Extracts of the luminal layer induced loss of anchorage of both cultured human smooth muscle cells and stromal cells of bone marrow origin (anoikis). This anoikis was prevented by preincubation of the extracts with serine protease inhibitors. Moreover, adhesion of human SMCs and stromal bone marrow cells on fibrin gels was strongly inhibited when the gel was preincubated with pure elastase, medium of fMLP-stimulated PMNs, or extracts of luminal layers of mural thrombi. This loss of cell anchorage was prevented by the preincubation of the medium or extracts with alpha(1)-antitrypsin, but not when alpha(1)-antitrypsin was added after binding of elastase to the fibrin gel. In conclusion, elastase released by PMNs trapped within the mural thrombus impairs the spontaneous anchorage of mesenchymal cells to a fibrin matrix. This phenomenon could be one mechanism by which cellular healing of the mural thrombus in aneurysms is prevented.  相似文献   

7.
Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau–Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.  相似文献   

8.
Development and progression of acquired abdominal aortic aneurysms (AAAs) involve proteolytic activity. In the present study, we investigate the distribution of fibrinolytic system components within mural thrombi of human AAAs. 20 mural thrombi and the remaining AAA walls were dissected. The luminal, intermediate and abluminal thrombus layers, and media and adventitia were separately incubated in cell culture medium. Conditioned media were then analysed for plasminogen activators (PAs), plasminogen activator inhibitor-1 (PAI-1), free-plasmin, plasmin alpha(2)-antiplasmin complexes (PAPs) and D-dimers release. In parallel, PA and PAI-1 mRNA expression analysis was performed by RT-PCR. The study was completed by immunohistochemical localization of these components in AAA, ex vivo functional imaging using (99m)Tc-aprotinin as a ligand and measurement of PAP and D-dimer plasma levels. All fibrinolytic system components were present in each aneurysmal layer. However, the mural thrombus was the main source of active serine-protease release. Interestingly, the luminal layer of the thrombus released greater amounts of PAPs and D-dimers. This paralleled the preferential immunolocalization of plasminogen and PAs, and the (99m)Tc-aprotinin scintigraphic signal observed in the luminal pole of the thrombus. In contrast, mRNA expression analysis showed an exclusive synthesis of tPA and PAI-1 within the wall, whereas uPA mRNA was also expressed within the thrombus. Taken together, these results suggest that the increased plasma concentrations of PAPs and D-dimers found in AAA patients are related to mural thrombus proteolytic activity, thus explaining their known link with AAA progression. Components of the fibrinolytic system could also represent a target for functional imaging of thrombus activities in AAA.  相似文献   

9.
腹主动脉瘤(abdominal aortic aneurysm,AAA)是腹主动脉局部呈肿瘤状扩张的血管疾病。如果不及时治疗,持续扩张的AAA将最终破裂,具有极高的死亡率。近年来,生物力学方法被广泛地应用于AAA临床破裂风险的评估预测中。相关研究成果也极大地增进了对于AAA病理机制的理解。首先讨论基于腔内血栓和AAA的生物力学测试方法,全面了解血栓及动脉瘤组织的多种力学特性以及力学特性变化对AAA在病理环境下生长及结构重建的影响;回顾一系列运用实验和计算生物力学手段预测AAA破裂风险的代表性研究成果,具体包括有限元分析AAA的管壁应力分布、评估破裂风险指数和判断破裂发生的具体位置等方面;重点阐述AAA中血栓的老化所导致的微观结构变化,并总结AAA生物力学研究的现状和未来挑战。  相似文献   

10.
The objective here was to experimentally characterize the temporal evolution of the structural and mechanical properties of large volume immature regenerated tissues. We studied these evolving tissues from their genesis in controlled mechanical conditions. We developed an animal model based on the periosteal properties leading to unloaded regenerated skeletal tissue. To characterize the temporal evolution of mechanical properties, we carried out indentation tests coupled with macroscopic examinations and histological studies. This combined methodology yielded a range of information on osteogenesis at different scales: macroscopic by simple observation, mesoscopic by indentation test and microscopic by histological study. Results allowed us to identify different periods, providing a link between biological changes and material property evolution in bone tissue regeneration. The regenerated tissue evolves from a viscous, homogeneous, soft material to a heterogeneous stiffer material endowed with a lower viscosity. From a biological point of view, cell organization progresses from a proliferated cell clot to a mature structure closer to that of the bone. During the first 7 days, mechanical and biological results revealed the same evolution: first, the regenerated tissue grew, then, differentiated into an osteochondral tissue and finally calcification began. While our biological results confirm those of other studies, our mechanical results provide the first experimental mechanical characterization by reduced Young’s modulus of such tissue.  相似文献   

11.
We extended the model describing the low molecular weight electron dense tracer wake in the interendothelial cleft and surrounding tissue to describe the time-dependent transport of intermediate size solutes of 1.0–3.5 nm radius by convection and diffusion in an interendothelial cleft containing a fiber matrix. This model provides a quantitative basis on which to reinterpret electron microscopic studies of the distribution of tracers such as horseradish peroxidase (HRP; molecular weight=40,000; Stokes radius =3.0 nm) along the interendothelial cell cleft from the lumen to the tissue for example, we show that, in contrast to our results with low molecular weight tracers, the wake of large molecular weight tracers on the abluminal side of the junctional strand is not likely to be detected, because the concentration of the tracer is predicted to be very low in most experiments. Thus the lack of a tracer such as HRP on the abluminal side of the junctional strand and in the tissue is not as strong evidence against the presence of a cleft pathway as suggested previously. The model does provide the basis for the design of experiments to locate both the principal molecular sieve and breaks in the junctional strand from the standing gradient on the luminal side of the junctional strand. An important experimental variable is the pressure in the vessel lumen which can be varied between 0 and 30 cm H2O to change the contributions of diffusive and convective transport to transcapillary exchange through the interendothelial cleft. This approach will also allow the testing of models for transcapillary pathways for large molecules by measuring the distribution of fluorescent tracers across the microvessel wall and in the tissue surrounding the microvessel using confocal microscopy.  相似文献   

12.
Optical microscopy encompasses high-resolution imaging techniques that can be used to non-destructively investigate and characterize living biological systems and engineered tissue constructs in culture. In particular, nonlinear optical microscopy (NLOM) is well suited for the visualization and quantification of processes involved in cell-extracellular matrix interactions in vivo. Current NLOM technology enables concomitant molecular imaging and visualization of microstructural organization that could provide a direct link between signal transduction and biological effect at microscopic length scales that culminate into tissue macroscopic properties and function. This review highlights the fundamentals of nonlinear optical interactions between light and tissue and presents a direction for future technology development to better complement quantitative, high-throughput assays of the modern life sciences.  相似文献   

13.
Abdominal aortic aneurysm (AAA) is a condition where the weakening of the aortic wall leads to its widening and the generation of a thrombus. To prevent a possible rupture of the aortic wall, AAA can be treated non-invasively by means of the endovascular aneurysm repair technique (EVAR), consisting of placing a stent-graft inside the aorta by a cateter to exclude the aneurysm sac from the blood circulation. A major complication is the presence of liquid blood turbulences, called endoleaks, in the thrombus formed in the space between the aortic wall and the stent-graft. In this paper we propose an automatic method for the detection of type II endoleaks in computer tomography angiography (CTA) images. The lumen and thrombus in the aneurysm area are first segmented using a radial model approach. Then, these regions are split into Thrombus Connected Components (TCCs) using a watershed-based segmentation and geometric and image content-based characteristics are obtained for each TCC. Finally, TCCs are classified into endoleaks and non-endoleaks using a multilayer Perceptron (MLP) trained on manual labeled sample TCCs provided by experts.  相似文献   

14.
Low grade appendiceal mucinous neoplasm (LAMN) is the primary source of pseudomyxoma peritonei (PMP). PMP may develop after seemingly complete resection of primary tumor by appendectomy, which is unpredictable due to lack of reliable prognostic indicators. We retrospectively reviewed 154 surgically resected LAMNs to explore if any of the macroscopic and microscopic characteristics may be associated with increasing risk of PMP development. Our major findings include: (1) As compared to those without PMP, the cases that developed PMP were more frequent to have (a) smaller luminal diameter (<1 cm) and thicker wall, separate mucin aggregations, and microscopic perforation/rupture, all suggestive of luminal mucin leakage; (b) microscopic acellular mucin presenting on serosal surface and not being confined to mucosa; and (c) neoplastic epithelium dissecting outward beyond mucosa, however, with similar frequency of neoplastic cells being present in muscularis propria. (2) Involvement of neoplastic cells or/and acellular mucin at surgical margin did not necessarily lead to tumor recurrence or subsequent PMP, and clear margin did not absolutely prevent PMP development. (3) Coexisting diverticulum, resulted from neoplastic or non-neoplastic mucosa being herniated through muscle-lacking vascular hiatus of appendiceal wall, was seen in a quarter of LAMN cases, regardless of PMP. The diverticular portion of tumor involvement was often the weakest point where rupture occurred. In conclusion, proper evaluation of surgical specimens with search for mucin and neoplastic cells on serosa and for microscopic perforation, which are of prognostic significance, should be emphasized.  相似文献   

15.
Abdominal aortic aneurysm (AAA) disease is a degenerating process whose ultimate event is the rupture of the vessel wall. Rupture occurs when the stresses acting on the wall rise above the strength of the AAA wall tissue. The complex mechanical interaction between blood flow and wall dynamics in a three dimensional custom model of a patient AAA was studied by means of computational coupled fluid-structure interaction analysis. Real 3D AAA geometry is obtained from CT scans image processing. The results provide a quantitative local evaluation of the stresses due to local structural and fluid dynamic conditions. The method accounts for the complex geometry of the aneurysm, the presence of a thrombus and the interaction between solid and fluid. A proven clinical efficacy may promote the method as a tool to determine factual aneurysm risk of rupture and aid the surgeon to refer elective surgery patients.  相似文献   

16.
Aortic aneurysm is a leading cause of death in adults, often taking lives without any premonitory signs or symptoms. Adverse clinical outcomes of aortic aneurysm are preventable by elective surgical repair; however, identifying at-risk individuals is difficult. The objective of this study was to perform a predictive biomechanical analysis of ascending aortic aneurysm (AsAA) tissue to assess rupture risk on a patient-specific level. AsAA tissues, obtained intra-operatively from 50 patients, were subjected to biaxial mechanical and uniaxial failure tests to obtain their passive elastic mechanical properties. A novel analytical method was developed to predict the AsAA pressure-diameter response as well as the aortic wall yield and failure responses. Our results indicated that the mean predicted AsAA diameter at rupture was 5.6 ± 0.7 cm, and the associated blood pressure to induce rupture was 579.4 ± 214.8 mmHg. Statistical analysis showed significant positive correlation between aneurysm tissue compliance and predicted risk of rupture, where patients with a pressure-strain modulus ?100 kPa may be nearly twice as likely to experience rupture than patients with more compliant aortic tissue. The mechanical analysis of pre-dissection patient tissue properties established in this study could predict the “future” onset of yielding and rupture in AsAA patients. The analysis results implicate decreased tissue compliance as a risk factor for AsAA rupture. The presented methods may serve as a basis for the development of a pre-operative planning tool for AsAA evaluation, a tool currently unavailable.  相似文献   

17.
Experimental and simulation studies were conducted to noninvasively characterize abdominal aneurysms with ultrasound (US) elastography before and after endovascular treatment. Twenty three dogs having bilateral aneurysms surgically created on iliac arteries with venous patches were investigated. In a first set of experiments, the feasibility of elastography to differentiate vascular wall elastic properties between the aneurismal neck (healthy region) and the venous patch (pathological region) was evaluated on six dogs. Lower strain values were found in venous patches (p < 0.001). In a second set of experiments, 17 dogs having endovascular repair (EVAR) by stent graft (SG) insertion were examined three months after SG implantation. Angiography, color Doppler US, examination of macroscopic sections and US elastography were used. The value of elastography was validated with the following end points by considering a solid thrombus of a healed aneurysm as a structure with small deformations and a soft thrombus associated with endoleaks as a more deformable tissue: (1) the correlation between the size of healed organized thrombi estimated by elastography and by macroscopic examinations; (2) the correlation between the strain amplitude measured within vessel wall elastograms and the leak size; and (3) agreement on the presence and size of endoleaks as determined by elastography and by combined reference imaging modalities (angiography + Doppler US). Mean surfaces of solid thrombi estimated with elastography were found correlated with those measured on macroscopic sections (r = 0.88, p < 0.001). Quantitative strain values measured within the vessel wall were poorly linked with the leak size (r = 0.12, p = 0.5). However, the qualitative evaluation of leak size in the aneurismal sac was very good, with a Kappa agreement coefficient of 0.79 between elastography and combined reference imaging modalities. In summary, complementing B-scan and color Doppler, noninvasive US elastography was found to be potentially a relevant tool for aneurismal follow-up after EVAR, provided it allows geometrical and mechanical characterizations of the solid thrombus within the aneurismal sac. This elasticity imaging technique might help detecting potential complications during follows-up subsequent to EVAR.  相似文献   

18.
 The inner ear of mammals contains the vestibular apparatus which is involved in the maintenance of posture and balance. The tubular structure of the apparatus is bathed by the potassium-rich endolymph and sodium-rich perilymph in the luminal and abluminal compartments, respectively. The luminal compartment is lined by a continuous epithelium with islets of receptor organs, which separates the luminal from the abluminal compartment. The present work focuses on the epithelium, without the receptor organs, and shows that it can be reconstituted in culture. The epithelium from 4-day-old Wistar rats was grown on microporous membranes. High transepithelial electrical resistances (4000–6000 Ω·cm2)were achieved after 4–8 days in culture. The epithelium was characterized by the presence of cytokeratin, ZO-1 protein, occludin, and the presence of tight junctions and kinocilia. The transepithelial resistance of the cell monolayer withstood endolymph/perilymph dual bathing when the apical pole of the cells was in contact with endolymph, but collapsed in the reverse configuration. Weak but statistically highly significant basal to apical rubidium (86Rb) transport was observed. These findings show that this epithelium maintains its in vivo polarity and could enhance the potassium composition of endolymph up to maturity. This new culture model, in which dual bathing is possible, should enable further in vitro studies of the sensory vestibular epithelia. Received: 19 July 1998 / Received after revision: 10 December 1998 / Accepted: 18 December 1998  相似文献   

19.
The metallic stent has been widely used in endovascular treatment of intracranial aneurysms and arterial stenosis. Endothelialization at the neck of the aneurysm or stenotic lesion after stent deployment plays a pivotal role in preventing aneurysm recurrence, as well as local thrombus formation and restenosis. To deliver autologous endothelial cells and to promote the endothelialization on the luminal wall of the parent artery, we established an endothelial cell-seeded intracranial stent device. Endothelial cells were isolated from canine jugular vein and identified by FACS assay and immunohistochemistry. We demonstrated that the seeded endothelial cells formed a confluent endothelial layer on the stent's surface. After being brushed with 100 dyne/cm(2) of shear stress, we found that this endothelial layer remained intact for at least 48 h on the heparinized polymer coated stent, rather than the poly-lactic-acid coated stent (p < 0.05). The results suggest that an autologous endothelial cell-seeded stent may be a feasible and optimal tool for endothelial delivery during stenting and may overcome some limitations of the traditional bare stent in the treatment of intracranial aneurysms and arterial stenosis.  相似文献   

20.
Quantitative assessment of abdominal aortic aneurysm geometry   总被引:1,自引:0,他引:1  
Recent studies have shown that the maximum transverse diameter of an abdominal aortic aneurysm (AAA) and expansion rate are not entirely reliable indicators of rupture potential. We hypothesize that aneurysm morphology and wall thickness are more predictive of rupture risk and can be the deciding factors in the clinical management of the disease. A non-invasive, image-based evaluation of AAA shape was implemented on a retrospective study of 10 ruptured and 66 unruptured aneurysms. Three-dimensional models were generated from segmented, contrast-enhanced computed tomography images. Geometric indices and regional variations in wall thickness were estimated based on novel segmentation algorithms. A model was created using a J48 decision tree algorithm and its performance was assessed using ten-fold cross validation. Feature selection was performed using the χ2-test. The model correctly classified 65 datasets and had an average prediction accuracy of 86.6% (κ = 0.37). The highest ranked features were sac length, sac height, volume, surface area, maximum diameter, bulge height, and intra-luminal thrombus volume. Given that individual AAAs have complex shapes with local changes in surface curvature and wall thickness, the assessment of AAA rupture risk should be based on the accurate quantification of aneurysmal sac shape and size.  相似文献   

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