Biomechanic and Hemodynamic Perspectives in Abdominal Aortic Aneurysm Rupture Risk Assessment

Abdominal aortic aneurysms (AAAs) pose a significant source of mortality for the elderly, especially if they go on undetected and ultimately rupture. Therefore, elective repair of these lesions is recommended in order to avoid risk of rupture which is associated with high mortality. Currently, the risk of rupture and thus the indication to intervene is evaluated based on the size of the AAA as determined by its maximum diameter. Since AAAs actually present original geometric configurations and unique hemodynamic and biomechanic conditions, it is expected that other variables may affect rupture risk as well. This is the reason why the maximum diameter criterion has often been proven inaccurate. The biomechanical approach considers rupture as a material failure where the stresses exerted on the wall outweigh its strength. Therefore, rupture depends on the pointwise comparison of the stress and strength for every point of the aneurysmal surface. Moreover, AAAs hemodynamics play an essential role in AAAs natural history, progression and rupture. This chapter summarizes advances in AAAs rupture risk estimation beyond the “one size fits all” maximum diameter criterion

Geometric, biomechanical and molecular analyses of abdominal aortic aneurysm

Background Abdominal aortic aneurysm (AAA) is defined as a dilatation of the abdominal aorta of 30 mm in diameter or more. Main risk factors are smoking, age and male sex. Pathophysiological features include inflammation, smooth muscle cell loss and destruction of the extracellular matrix. The AAA is typically asymptomatic but can expand and eventually rupture, with a mortality of 70-80% as a result. Risk factors for rupture include a large diameter, female sex, active smoking, high blood pressure and low body mass index (BMI). There is no medical treatment to inhibit growth or rupture of AAA. The only measure to prevent rupture in a large AAA is aortic surgery. This intervention carries its own significant risk of morbidity and mortality, necessitating a risk stratification method. The diameter is currently used to decide when to operate on an AAA and it is repeatedly monitored until the threshold for surgery is reached. However, this measurement leaves room for improvement, as the individual aneurysm growth rate is difficult to predict and some large AAAs do not rupture while in other patients, small AAAs rupture during surveillance. Finite element analysis (FEA) is a method by which biomechanical rupture risk can be estimated based on patient characteristics and a computed tomography (CT)-derived 3D model of an AAA. Microarray analysis allows high-throughput analyses of tissue gene expression. Aims The overall aim of this thesis was to explore and develop new strategies to improve, refine and individualize management of patients with AAA, by applying geometric, biomechanical and molecular analyses. Methods and Results In study I, the CTs of 146 patients with AAAs of diameters between 40 and 60 mm were analyzed with three-dimensional (3D) segmentation and FEA. Simple and multiple regression analyses were performed. Female sex, patient height, lumen volume, body surface area (BSA) and low BMI were shown to be associated with the biomechanical rupture risk of AAA. Study II included 191 patients with AAAs of diameters between 40-50 mm. The AAAs were analyzed with 3D segmentation and FEA after which prediction algorithms were developed by use of machine learning strategies. More precise diameter measurements improved prediction of growth and four-year prognosis of small AAAs. Biomechanical indices and lumen diameter were predictive of future rupture or symptomatic AAA. Growth and rupture required different prediction models. In study III, 37 patients, 42 controls and a validation cohort of 51 patients were analyzed with respect to their circulating levels of neutrophil elastase-derived fibrin degradation products (E-XDP). The results showed that E-XDP was a sensitive marker for AAA, independently of examined comorbidities, and its concentration in peripheral blood correlated with the AAA diameter and the volume and mechanical stress of the intraluminal thrombus (ILT). It was further increased by the presence of coexisting aneurysms. Study IV included 246 tissue samples, divided into tunica media and adventitia, from 76 patients with AAA and 13 organ donor controls, analyzed by microarrays. There were large differences between the transcriptomes of AAA and control media and adventitia. Processes related to inflammation were transmural, whereas the upregulation of proteolysis, angiogenesis and apoptosis along with downregulation of smooth muscle- and differentiation-related gene sets were specific for the aneurysm media. Active smoking increased oxidative stress in all tissues and increased inflammation and lipid-related processes in AAA. The growth rate of the AAA diameter correlated with adaptive immunity in media and lipid processes in adventitia. Conclusions In this thesis, we show that known clinical risk factors and certain geometric properties are associated with biomechanical deterioration of AAAs. Furthermore, geometric and biomechanical analyses can enhance prediction of outcome. Importantly, there are differences between prediction of AAA growth and rupture. Finally, a biomarker was discovered and the transcriptome of AAA including effects of the ILT, smoking and rapid diameter growth rate, was mapped and we envision that the data may be used for future biomarker and drug target discovery

Biomechanical and morphological aspects of abdominal aortic aneurysm growth and rupture

Abdominal aortic aneurysms (AAAs) are dilatations of the abdominal aorta that pose a risk of rupture. The only effective treatment is intervention prior to rupture, but this is also associated with mortality and morbidity. It is therefore important to weigh the risks of intervention with the potential benefit. Current treatment guidelines recommend using the maximal aneurysm diameter (Dmax) as the indicator for rupture risk, and rec- ommend considering intervention in men with AAAs > 55 mm, and >50 mm in women. Patients with small AAAs are put in surveillance, and the Dmax is followed until it reaches the threshold. The current policy is relatively efficient on a population-level but lacks specificity for individuals. Some patients rupture before this threshold, and many remain stable despite passing it. Aneurysm growth is often described as erratic, but measure- ments are affected by several levels of uncertainty. Biomechanical assessment, where 3D models of AAAs from computed tomography angiographies (CTAs) are analysed by finite element analysis, may improve risk prediction. In the first study a population-based cohort of 192 patients with ruptured AAAs and CT imaging available at rupture were studied. A significant portion of patients ruptured with AAAs smaller than 60 mm, 10% of men and 27 % of women. When normalizing Dmax for body surface area (so-called aortic size index) there was, however, was not difference between the sexes. In an analysis of small, ruptured AAAs compared to Dmax, age and sex-matched asymptomatic AAAs, peak wall rupture index (PWRI), but not peak wall stress (PWS) was increased in the ruptured AAAs. In the second study, a cohort of 100 patients with at least three computed tomog- raphy examinations were analysed with 3D morphological and biomechanical analysis. The growth pattern of AAAs appeared continuous and conferred well to a linear growth model. The evolution of the different analysed indices, Dmax, aneurysm volume and bio- mechanical stress did, however, not parallel each other. Intraluminal thrombus (ILT) grew faster than the lumen, but lumen volume growth was more closely related to increase in biomechanical stress. In the third study, a cohort of 67 patients with 109 CTA examinations prior to rupture were identified. The relation between biomechanical variables and time-to-rupture was investigated. In small and medium sized AAAs (< 70 mm), PWRI, but not PWS, was associ- ated with time-to-rupture, also when adjusting for potential confounders, aneurysm size and sex. The results further show that women have an approximately two-fold increased hazard ratio for AAA rupture, compared to men, when adjusted for AAA size. In the fourth study lumen area is indicated as a potentially useful rupture risk marker. Ruptured AAAs, compared to Dmax-matched asymptomatic AAAs, have a larger luminal area, and the luminal area is related to biomechanical stress, even when adjusting for an- eurysm size, or ILT area. In conclusion, the results of this thesis indicate areas of potential improvement in the current care of patients with AAAs, explores the 3D growth of AAAs, and strengthens the potential role for biomechanical analysis. These results may in the future have rele- vance for personalizing timing of treatment for patients with AAAs, and the evaluation of pharmacological therapy for AAAs

Numerical Insights for AAA Growth Understanding and Predicting: Morphological and Hemodynamic Risk Assessment Features and Transient Coherent Structures Uncovering

Les anévrismes de l'aorte abdominale (AAA) sont des dilatations localisées et fréquentes de l'aorte. En cas de rupture, seul un traitement immédiat peut prévenir la morbidité et la mortalité. Le diamètre maximal AAA ($D_{max}$) et la croissance sont les paramètres actuels pour évaluer le risque associé et planifier l'intervention, avec des seuils inférieurs pour les femmes. Cependant, ces critères ne sont pas personnalisés ; la rupture peut se produire à un diamètre inférieur et les patients vivre avec un AAA important. Si l'on sait que la maladie est associée à une modification de la morphologie et de la circulation sanguine, à un dépôt de thrombus intra-luminal et à des symptômes cliniques, les mécanismes de croissance ne sont pas encore entièrement compris. Dans cette étude longitudinale, une analyse morphologique et des simulations de flux sanguins sont effectuées et comparées aux sujets témoins chez 32 patients ayant reçu un diagnostic clinique d'AAA et au moins 3 tomodensitogrammes de suivi par patient. L'objectif est d'abord d'examiner quels paramètres stratifient les patients entre les groupes sains, à faible risque et à risque élevé. Les corrélations locales entre les paramètres hémodynamiques et la croissance de l'AAA sont également explorées, car la croissance hétérogène de l'AAA n'est actuellement pas comprise. Enfin, les paramètres composites sont construits à partir de données cliniques, morphologiques et hémodynamiques et de leur capacité à prédire si un patient sera soumis à un test de risque. La performance de ces modèles construits à partir de l'apprentissage supervisé est évaluée par les ROC AUC : ils sont respectivement de 0.73 ± 0.09, 0.93 ± 0.08 et 0.96 ± 0.10 . En incorporant tous les paramètres, on obtient une AUC de 0.98 ± 0.06. Pour mieux comprendre les interactions entre la croissance et la topologie de l'écoulement de l'AAA, on propose un worflow spécifique au patient pour calculer les exposants de Lyapunov en temps fini et extraire les structures lagrangiennes-cohérentes (SLC). Ce modèle de calcul a d'abord été comparé à l'imagerie par résonance magnétique (IRM) par contraste de phase 4-D chez 5 patients. Pour mieux comprendre l'impact de la topologie de l'écoulement et du transport sur la croissance de l'AAA, des SLC hyperboliques répulsives ont été calculées chez un patient au cours d'un suivi de 8 ans, avec 9 mesures morphologiques volumétriques de l'AAA par tomographie-angiographie. Les SLC ont défini les frontières du jet entrant dans l'AAA. Les domaines situés entre le SLC et le mur aortique ont été considérés comme des zones de stagnation. Leur évolution a été étudiée lors de la croissance de l'AAA. En plus des SLC hyperboliques (variétés attractives et répulsives) découvertes par FTLE, les SLC elliptiques ont également été considérées. Il s'agit de régions dominées par la rotation, ou tourbillons, qui sont de puissants outils pour comprendre les phénomènes de transport dans les AAA.Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of the aorta. In the event of rupture only immediate treatment can prevent morbidity and mortality. The AAA maximal diameter ($D_{max}$) and growth are the current metrics to evaluate the associated risk and plan intervention, with lower thresholds for women. However, these criteria lack patient specificity; rupture may occur at lower diameter and patients may live with large AAA. If the disease is known to be associated with altered morphology and blood flow, intra-luminal thrombus deposit and clinical symptoms, the growth mechanisms are yet to be fully understood. In this longitudinal study, morphological analysis and blood flow simulations for 32 patients with clinically diagnosed AAA and at least 3 follow-up CT-scans per patient, are performed and compared to control subjects. The aim is first to investigate which metrics stratify patients between healthy, low risk and high risk groups. Local correlations between hemodynamical metrics and AAA growth are also explored, as AAA heterogeneous growth is currently not understood. Finally, composite metrics are built from clinical, morphological, and hemodynamical data, and their ability to predict if a patient will become at risk tested. Performance of these models built from supervised learning is assessed by ROC AUCs: they are respectively, 0.73 ± 0.09, 0.93 ± 0.08 and 0.96 ± 0.10. Mixing all metrics, an AUC of 0.98 ± 0.06 is obtained. For further insights into AAA flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) on 5 patients. To better understand the impact of flow topology and transport on AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-years follow-up, including 9 volumetric morphologic AAA measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during AAA growth. In addition to hyperbolic (attracting and repelling) LCS uncovered by FTLE, elliptic LCS were also considered. Those encloses rotation-dominated regions, or vortices, which are powerful tools to understand the flow transport in AAA

In vivo quantification of metabolic activity in aortic aneurysms using PET

Objective: To investigate the role of hybrid 18F-FDG PET/CT as a potential risk-stratification tool of aneurysm expansion by measuring metabolic activity on PET and textural analysis on CT in abdominal aortic aneurysm (AAA). Histological markers of AAA wall inflammatory cell infiltrate and enzymatic degradation have been associated with increased 18F-Fluorodeoxyglucose (18F-FDG)-Positron Emission Tomography /Computed Tomography (PET/CT) uptake. Methods: Fifty patients with asymptomatic infrarenal AAA enrolled under surveillance at one of our institutions underwent 18F-FDG-PET/CT. Seventeen subjects were investigated for increased glucolysis in the AAA wall and optimal circulation imaging time for 18F-FDG. In 25 subjects the relationship between aneurysm metabolic activity and expansion was explored. Forty subjects had AAA CT textural analysis (CTTA) parameters performed on the CT component of PET/CT and were studied in relation to aneurysm expansion. Twenty-four subjects had circulating biomarkers analysed. Whole vessel assessment, region of interest analysis and the role of correcting for background blood pool activity were explored. Results: Thirteen of seventeen subjects investigated for increased 18F-FDG uptake had an AAA wall SUVmax > 2.5. In 17 subjects assessed for optimal circulation imaging time for 18F-FDG, no significant advantage in imaging at 3h over 1h after 18F-FDG injection was observed. 18F-FDG uptake correlated inversely with future AAA expansion in the preliminary group of 25 patients and in 40 subjects who also had CTTA. In subjects who had CTTA, coarse texture showed an inverse association with 18F-FDG uptake and medium coarse texture correlated with future AAA expansion. In 24 AAA patients who had serum biomarker assays, significantly higher levels of high sensitivity matrix metalloproteinase-9 (hsMMP-9) and hsMMP-2 compared to healthy controls were found. There was no correlation between AAA 18F-FDG uptake and levels of hsMMP-9, hsMMP-2, hs-interferon-γ and hs-C-reactive protein. Conclusions: In-vivo 18F-FDG PET/CT data indicated that small AAA show increased glucose metabolism. Relationships between AAA 18F-FDG uptake, CTTA and future expansion were identified. AAA18F-FDG PET/CT shows potential to identify subjects at risk of significant expansion. AAA metabolism may not relate to serum levels of certain inflammatory biomarkers

Abdominal aortic aneurysms : identification by self-examination and analysis of variation in matrix metalloproteinases with peak wall stress

Abdominal aortic aneurysms (AAAs) cause 5,000 deaths a year in the UK. Self-examination for AAAs may provide an economic and practical solution. Matrix metalloproteinase (MMP) concentration is elevated and levels of their natural inhibitors - Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) are reduced at sites of AAA rupture. Finite element analysis (FEA) of AAAs can define the area of peak wall stress area, the most likely site of rupture in engineering terms.Study 1Aim: To assess the effectiveness of self-examination for detection of AAAs compared to ultrasound measurement. The psychological consequences were also evaluated.6,888(65%) of 10,591 male patients aged ≥65 years who were invited to participate, joined the study.The sensitivity of self-examination for all AAAs (≥3cm) was 37% and for clinically significant AAAs (≥5cm) was 49%. Specificities were 80% and 79% respectively.The psychological consequences of screening were assessed with the HAD (Hospital Anxiety and Depression) scale. There was no clinical anxiety or depression but there was a statistically significant reduction in both domains on completion.Self-examination for AAAs cannot be recommended as an effective screening tool.Study 2Aim: To assess the tissue concentration of MMPs & TIMPs in AAAs at the site of peak wall stress.22 patients undergoing elective AAA repair had FEA performed on their CT scans, identifying the peak stress site. Biopsies from this site and the arteriotomy site were stored at -80°C, and tested for MMP & TIMP concentrations with an enzyme linked immunosorbent assay (ELISA).No significant difference was found between the 2 sites for MMP2, 8, 9, TIMP1 or 2.These findings suggest either that the peak stress and rupture sites are geographically different, or that the event of rupture is temporally related to a fundamental biochemical change

Automatic classification and 3D visualisation of abdominal aortic aneurysms to predict aneurysm expansion

Abdominal aortic aneurysms (AAA) are a major cause of death in men above the age of 65 in the western world. Currently decisions for AAA management are based on the size of maximum AAA diameter (>5.5cm), measured using ultrasound imaging. However, as a proportion of AAAs rupture whilst still below this diameter threshold, while larger AAAs may never rupture, better methods for AAA expansion and rupture prediction are required. Previous research suggested that the presence of “hotspots” (focal areas) of inflammation as detected with USPIO-enhanced MRI may have potential in identifying faster-growing AAAs. However, the identification of these USPIO “hotspots” had been up to this point restricted to manual processing of the MRI data in a time-consuming and laborious slice-by-slice method, which only used 2D information. Inter- and intra- observer variability were an issue, as well as the use of empirically-defined signal thresholds which were dependent on each acquisition protocol. The work presented in this thesis aimed to evaluate current methodologies for AAA assessment and growth prediction and to contribute to improved prediction models by introducing novel techniques. Ultrasound was found to under-measure AAA size and the use of maximum AAA diameter was found to be problematic, especially for growth calculations. Automatically calculated alternatives which account for the total size and shape of the AAA, as measured with MRI, were introduced for more reproducible measurements. Furthermore, automation and standardisation of the previously-employed manual methods for hotspot detection and AAA classification were achieved, with the development of an efficient algorithm with excellent agreement levels. Taken a step further, two improved algorithms were introduced, adaptive to the data and USPIO distribution of individual AAAs and eliminating the universal threshold previously used. These algorithms incorporated information on 3D USPIO distribution along the length of the AAAs to detect and visualise 3D hotspots of inflammation for the first time. Novel 2D and 3D metrics were introduced, while the algorithms were also incorporated into a GUI for ease of clinical use. Additional aneurysm metrics automatically derived by the algorithms were incorporated into multiple linear regression models to investigate prediction of AAA growth rate. This investigation introduced three significant predictors which have not been used in previous predictive models of AAA expansion: the “mean thrombus major axis” metric, which reflected baseline size of AAA throughout multiple axial slices of the AAA; the “eccentricity WT” metric which reflected the relationship between wall shape and thrombus; and the presence of “3D hotspots” which may potentially reflect transported USPIO within a network of vascular channels along the length of the aneurysm. In line with previous literature, family history of AAA and high diastolic BP were also found to be significant predictors, but larger cohorts are needed for more reliable assessment of the predictive models suggested in this thesis

Determination of biomechanical, anatomical and patophysiological factors influencing wall strength of the abdominal aortic aneurysm and their role in the abdominal aortic aneurysm rupture risk assessment

Uvod. Aneurizma abdominalne aorte je potencijalno fatalno oboljenje koje se preventivno može lečiti hirurški. Rizik od hirurškog lečenja je sve manji međutim ma koliko bile retke komplikacije mogu biti fatalne ili prouzrokovati težak invaliditet. Upravo zato je od velikog značaja poznavanje rizika od rutpure aeurizme koji se trenutno procenjuje samo na osnovu najvećeg prečnika aneurizme što se pokazuje kao nedovoljno precizno. Ispitivanje uticaja drugih parametara (biomehaničkih, anatomskih, patomorfoloških) na nastanak rupture bi moglo da napredi procenu rizika od ove fatalne komplikacije. Metod. Ispitivanje je sprovedeno po tipu prospektivne studije koja je obuhvatila 288 bolesnika sa aneurizmom abdominalne aorte koji su ispitivani ili operisani na Klinici za vaskularnu i endovaskularnu hirurgiju KCS u periodu od januara 2012 do decembra 2015 godine. Na osnovu podataka dobijenih multislajsnom kompjuterizovanom tomografijom kod bolesnika su ispitivani biomehanički parametri koji deluju na zid aneurizme (napon, prečnik ekvivalentan riziku od rupture) kao i morfoloki parametri koji bi mogli da ukažu na patofiziološke procese u aneurizmatskoj kesi (zapreminu aneurizme, intraluminalnog tromba, angulacije). Uzorci prednjeg zida aneurizmatske kese ispitivani su testom inflacije i na taj način im je određivana snaga i elastičnost dok je iz uzorka seruma odreživana aktivnost matriksne metaloproteinaze 9. Rezultati. Značajno više osoba ženskog pola je bilo u grupi bolesnika sa simptomatskom odnosno rupturiranom aneurizmom abdominalne aorte, 5/23 (21.73%) prema 12/75 (16%), p=0.005. Multivarijantni model kojim su uključeni pol, životna dob, maksimalni prečnik aneurizme (MAD,OR=1.063), relativna zapremina intraluminalnog tromba (rILT, OR=1.039) i ukupna zapremina aneurizme (UZA,OR=1.006) su značajni prediktori rupture aneurizme abdominalne aorte sa najvećim naponom u zidu (PWS,OR=1.010) dijametra ekvivalentan riziku od rupture (RRED,OR=1.031). Merene su vrednosti AUC i cc za iste parametre u modelu koji kombinuje MAD, TZA i rILT: MAD (0.790, cc=75%), PWS (0.713, cc=73%), RRED (0.717, cc=55%), TAV (0.756, cc=79%), rILT (0.656, cc=60%) i MAD+TAV+rILT (0.797, cc=82%). Nije dobijena statistički značajna razlika između vrednosti serumske MMP 9 i snage zida, test korelacije je iznosio 0.174, p=0.135. Konstatovana je statistički značajna povezanost između serumske koncentracije MMP 9 i srednjeg napona u intraluminalnom trombu (cc - 0.371, p=0.016), najvećeg rizika od rupture (p=0.04) i volumena intraluminalnog tromba (cc 0.324, p=0.03). Zaključak. Imajući u vidu zadate ciljeve kao i prikazane rezultate može se zaključiti da je zid aneurizme abdominalne aorte slabije snage kod aneurizmi koje su već rupturirale ili izazivale simptome čime je pokazano da snaga zida ima važnu ulogu u procesu nastanka rupture. Na snagu aneurizmatskog zida je uticala jedino relativna debljina intraluminalnog tromba. Serumska koncetracija MMP – 9 se, prema rezultatima ovog istraživanja, ne može koristiti za procenu snage aneurizmatskog tkiva prilikom predviđanja rizika od rupture aneurizme abdominalne aorte. Biomehanički, anatomski odnosno morfološki parametri mogu začajno unaprediti predviđanje rizika od rupture u odnosu na korišćenje samog dijametra. Najkorisniji su najveći napon, zapremina aneurizme, relativna zapremina intraluminalnog tromba i dijametar ekvivalentan riziku od rupture. Korišćenjem ovih parametara moć predviđanja nastanka rupture se povećava sa 73% na 83.9%.Introduction. Abdominal aortic aneurysm is potentialy fatal disease that can be treated with preventive operation. Surgical risk, although improving, can lead to death or disability. In this regard it is of high importance to assess risk of rupture that is nowdays expressed in correlation to aneurysm diameter what was shown to be less accurate. Assessment of correlation between other parameters (biomechanical, anatomical, patomorphological) and risk of aneurysm rupture might improve rupture risk assesment and facilitate decision making. Methods. This research was conducted in prospective manner at the Clinic for Vascular and Endovascular surgery and included 288 patients with abdominal aortic aneurysm in the period from January 2012 to December 2015. Images from multisliced computed tomography were used for biomechanical analysys to estimate peak wall stress and rupture risk equvivalent diameter by finite element analysys. Morphological parameters as aneurysm and intraluminal thrombus volume, angulations and anatomical parmeters were assessed from these images as well. Samples of anterior wall of aneurysm were tested with inflation test estimating tissue elasticity and strength while serum level of matrix metalloproteinase 9 were measured as well. Results. There were significantly more females in the R group: 5/23 (21.73%) comparing to 12/75 (16%) in 4A group, p=0.005. In a multivariable model, including gender and age as confounder variables, maximal aneurysm diameter (MAD,OR= 1.063), relative intraluminal thrombus (rILT,OR=1.039) and total aneurysm (TAV,OR=1.006) volume continued to be a significant predictors of AAA rupture with peak wall stress (PWS,OR=1.010) and rupture risk equivalent diameter (RRED,OR=1.031). AUC values and correct classification (cc) for the same parameters and model that combines MAD, TAV and rILT were measured: MAD (0.790, cc=75%), PWS (0.713, cc=73%), RRED (0.717, cc=55%), TAV (0.756, cc=79%), rILT (0.656, cc=60%) and MAD+TAV+rILT (0.797, cc=82%) Conclusion. Based on aim and presented results aneurysm wall is weaker in ruptured and symptomatic aneurysm outlining importance of wall strength in rupture developement. Wall strength correlated with relative thrombus thickness. Serum level of MMP-9, based on these restults, can not be used for tissue strength assessment however thrombus formation can be suspected in elevated levels of MMP 9. Biomechanical, anatomical and moprhological paramters can improve rupture prediction in comparison to maximal diameter only. The most usefull paramters are peak wall stress, aneurysm volume, relative intraluminal thrombus and rupture risk equivalent diameter. Using these paramters rupture prediction is increased from 73% to 83.9%

Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes