Analysis and computer program for rupture-risk prediction of abdominal aortic aneurysms

BACKGROUND: Ruptured abdominal aortic aneurysms (AAAs) are the 13(th )leading cause of death in the United States. While AAA rupture may occur without significant warning, its risk assessment is generally based on critical values of the maximum AAA diameter (>5 cm) and AAA-growth rate (>0.5 cm/year). These criteria may be insufficient for reliable AAA-rupture risk assessment especially when predicting possible rupture of smaller AAAs. METHODS: Based on clinical evidence, eight biomechanical factors with associated weighting coefficients were determined and summed up in terms of a dimensionless, time-dependent severity parameter, SP(t). The most important factor is the maximum wall stress for which a semi-empirical correlation has been developed. RESULTS: The patient-specific SP(t) indicates the risk level of AAA rupture and provides a threshold value when surgical intervention becomes necessary. The severity parameter was validated with four clinical cases and its application is demonstrated for two AAA cases. CONCLUSION: As part of computational AAA-risk assessment and medical management, a patient-specific severity parameter 0 < SP(t) < 1.0 has been developed. The time-dependent, normalized SP(t) depends on eight biomechanical factors, to be obtained via a patient's pressure and AAA-geometry measurements. The resulting program is an easy-to-use tool which allows medical practitioners to make scientific diagnoses, which may save lives and should lead to an improved quality of life

Non-linear viscoelastic behavior of abdominal aortic aneurysm thrombus

The objective of this work was to determine the linear and non-linear viscoelastic behavior of abdominal aortic aneurysm thrombus and to study the changes in mechanical properties throughout the thickness of the thrombus. Samples are gathered from thrombi of seven patients. Linear viscoelastic data from oscillatory shear experiments show that the change of properties throughout the thrombus is different for each thrombus. Furthermore the variations found within one thrombus are of the same order of magnitude as the variation between patients. To study the non-linear regime, stress relaxation experiments are performed. To describe the phenomena observed experimentally, a non-linear multimode model is presented. The parameters for this model are obtained by fitting this model successfully to the experiments. The model cannot only describe the average stress response for all thrombus samples but also the highest and lowest stress responses. To determine the influence on the wall stress of the behavior observed the model proposed needs to implemented in the finite element wall stress analysis

Fluid-structure interaction in abdominal aortic aneurysms: effects of asymmetry and wall thickness

BACKGROUND: Abdominal aortic aneurysm (AAA) is a prevalent disease which is of significant concern because of the morbidity associated with the continuing expansion of the abdominal aorta and its ultimate rupture. The transient interaction between blood flow and the wall contributes to wall stress which, if it exceeds the failure strength of the dilated arterial wall, will lead to aneurysm rupture. Utilizing a computational approach, the biomechanical environment of virtual AAAs can be evaluated to study the affects of asymmetry and wall thickness on this stress, two parameters that contribute to increased risk of aneurysm rupture. METHODS: Ten virtual aneurysm models were created with five different asymmetry parameters ranging from β = 0.2 to 1.0 and either a uniform or variable wall thickness to study the flow and wall dynamics by means of fully coupled fluid-structure interaction (FSI) analyses. The AAA wall was designed to have a (i) uniform 1.5 mm thickness or (ii) variable thickness ranging from 0.5 – 1.5 mm extruded normally from the boundary surface of the lumen. These models were meshed with linear hexahedral elements, imported into a commercial finite element code and analyzed under transient flow conditions. The method proposed was then compared with traditional computational solid stress techniques on the basis of peak wall stress predictions and cost of computational effort. RESULTS: The results provide quantitative predictions of flow patterns and wall mechanics as well as the effects of aneurysm asymmetry and wall thickness heterogeneity on the estimation of peak wall stress. These parameters affect the magnitude and distribution of Von Mises stresses; varying wall thickness increases the maximum Von Mises stress by 4 times its uniform thickness counterpart. A pre-peak systole retrograde flow was observed in the AAA sac for all models, which is due to the elastic energy stored in the compliant arterial wall and the expansion force of the artery during systole. CONCLUSION: Both wall thickness and geometry asymmetry affect the stress exhibited by a virtual AAA. Our results suggest that an asymmetric AAA with regional variations in wall thickness would be exposed to higher mechanical stresses and an increased risk of rupture than a more fusiform AAA with uniform wall thickness. Therefore, it is important to accurately reproduce vessel geometry and wall thickness in computational predictions of AAA biomechanics

Investigation of the Hemodynamic Effect of Stent Wires on Renal Arteries in Patients with Abdominal Aortic Aneurysms Treated with Suprarenal Stent-Grafts

The purpose of the study was to investigate the hemodynamic effect of stent struts (wires) on renal arteries in patients with abdominal aortic aneurysms (AAAs) treated with suprarenal stent-grafts. Two sample patients with AAA undergoing multislice CT angiography pre- and postsuprarenal fixation of stent-grafts were selected for inclusion in the study. Eight juxtarenal models focusing on the renal arteries were generated from the multislice CT datasets. Four types of configurations of stent wires crossing the renal artery ostium were simulated in the segmented aorta models: a single wire crossing centrally, a single wire crossing peripherally, a V-shaped wire crossing centrally, and multiple wires crossing peripherally. The blood flow pattern, flow velocity, wall pressure, and wall shear stress at the renal arteries pre- and post-stent-grafting were analyzed and compared using a two-way fluid structure interaction analysis. The stent wire thickness was simulated with a diameter of 0.4, 1.0, and 2.0 mm, and hemodynamic analysis was performed at different cardiac cycles. The interference of stent wires with renal blood flow was mainly determined by the thickness of stent wires and the type of configuration of stent wires crossing the renal ostium. The flow velocity was reduced by 20–30% in most of the situations when the stent wire thickness increased to 1.0 and 2.0 mm. Of the four types of configuration, the single wire crossing centrally resulted in the highest reduction of flow velocity, ranging from 21% to 28.9% among three different wire thicknesses. Wall shear stress was also dependent on the wire thickness, which decreased significantly when the wire thickness reached 1.0 and 2.0 mm. In conclusion, our preliminary study showed that the hemodynamic effect of suprarenal stent wires in patients with AAA treated with suprarenal stent-grafts was determined by the thickness of suprarenal stent wires. Research findings in our study are useful for follow-up of patients treated with suprarenal stent-grafts to ensure long-term safety of the suprarenal fixation

Lesson learned from early and long-term results of 327 cases of coexisting surgical abdominal diseases and aortic aneurysms treated in open and endovascular surgery

Patients with abdominal aortic aneurysm (AAA) frequently have other abdominal pathologies of surgical interest (other diseases, OD). Out of 1,375 elective open aortic replacements for AAA, 315 cases with OD were subdivided in Group 1 (82 patients with “clean wound” OD) and Group 2 (233 patients with “clean-contaminated wound” OD). The results of the sub-groups in which OD was treated at the same time as AAA were analysed (1a, 66 cases and 2a, 86 cases) and compared with OD not treated at the same time as AAA (1b, 16 cases and 2b, 147 cases). EVAR was done in 12 patients with a infrarenal AAA and concomitant abdominal disease. In this group post-operative complications occured in two patients (endoleaks) and no sign of endograft infection was developed. Mean follow-up was 36 months. Mortality was 0% in Group 1a, 1b, 2b and 5.8% in Group 2a. In Group 1a there were one haemoperitoneum, one ischaemic colitis and one graft infection. In Group 1b there were 4 nefrectomies for renal carcinoma and three emergency hernia repairs within 18 months from AAA operation. In Group 2a the follow-up was uneventful. In Group 2b there was no acute complication of OD and 57.2% of patients were subsequently operated for OD. In the EVAR group the 30-day and late mortality rates were 0 and 25%, respectively and all deaths were cancer-related. Contemporary correction of OD in open surgery for AAA should be performed in clean wound cases, while clean-contaminated operations can be done only in selected cases. EVAR is a valid alternative technique to open vascular surgery for the concomitant treatment of aortic aneurysms and abdominal pathologies

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate

Disruption of Yarrowia lipolytica TPS1 Gene Encoding Trehalose-6-P Synthase Does Not Affect Growth in Glucose but Impairs Growth at High Temperature

We have cloned the Yarrowia lipolytica TPS1 gene encoding trehalose-6-P synthase by complementation of the lack of growth in glucose of a Saccharomyces cerevisiae tps1 mutant. Disruption of YlTPS1 could only be achieved with a cassette placed in the 3′half of its coding region due to the overlap of its sequence with the promoter of the essential gene YlTFC1. The Yltps1 mutant grew in glucose although the Y. lipolytica hexokinase is extremely sensitive to inhibition by trehalose-6-P. The presence of a glucokinase, insensitive to trehalose-6-P, that constitutes about 80% of the glucose phosphorylating capacity during growth in glucose may account for the growth phenotype. Trehalose content was below 1 nmol/mg dry weight in Y. lipolytica, but it increased in strains expressing YlTPS1 under the control of the YlTEF1promoter or with a disruption of YALI0D15598 encoding a putative trehalase. mRNA levels of YlTPS1 were low and did not respond to thermal stresses, but that of YlTPS2 (YALI0D14476) and YlTPS3 (YALI0E31086) increased 4 and 6 times, repectively, by heat treatment. Disruption of YlTPS1 drastically slowed growth at 35°C. Homozygous Yltps1 diploids showed a decreased sporulation frequency that was ascribed to the low level of YALI0D20966 mRNA an homolog of the S. cerevisiae MCK1 which encodes a protein kinase that activates early meiotic gene expression