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  • 1.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Bringing vascular biomechanics into clinical practice. Simulation-based decisions for elective abdominal aortic aneurysms repair2012In: Lecture Notes in Computational Vision and Biomechanics, ISSN 2212-9391, E-ISSN 2212-9413, Vol. 5, p. 1-37Article in journal (Refereed)
    Abstract [en]

    Vascular diseases are the leading cause of death in the industrialized countries and some of the associated risk factors are increasing. A multi-disciplinary approach including biomechanics is needed to better understand and more effectively treat these diseases. Despite the tremendous progress made in modeling the biomechanics of the vasculature, so far this research has accomplished only very limited clinical relevance or acceptance. Establishing vascular biomechanical simulations in the clinical work-flow requires integrating (i) a robust reconstruction of vascular bodies from medical images, (ii) a non-linear biomechanical analysis and (iii) a clinically relevant interpretation of the derived results. Such an approach is outlined for the biomechanical rupture risk assessment of Abdominal Aortic Aneurysms (AAAs), i.e. a local dilatation of the infrarenal aorta that may form through irreversible pathological remodeling of the aortic wall. Rupture of an AAA is a frequent cause of death in the elderly male population and assessing this risk plays a central role in the clinical management of aneurysms. Specifically, the present chapter details an operator-insensitive method to reconstruct vascular bodies from Computer Tomography-Angiography data. The approach is based on beam and shell-like deformable (active) contour models and allows a hexahedral-dominated mesh generation for an efficient Finite Element computation. Laboratory experiments and histo-mechanical constitutive modeling of AAA tissue are reviewed. Finally, the clinical application of the biomechanical rupture risk assessment is demonstrated through the especially developed software A4clinics. Most critically, individual biomechanical parameters are related to the ‘average AAA patient’, which in turn provides a biomechanics-based index for elective AAA repair indication. © 2012, Springer Science+Business Media Dordrecht.

  • 2.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Damage in vascular tissues and its modeling2017In: CISM International Centre for Mechanical Sciences, Courses and Lectures, Springer International Publishing , 2017, p. 85-118Chapter in book (Refereed)
    Abstract [en]

    The present chapter reviews vessel wall histology and summarizes relevant continuum mechanical concepts to study mechanics-induced tissue damage. As long as the accumulated damage does not trigger strain localizations, the standard nonpolar continuum mechanical framework is applicable. As an example, a damage model for collagenous tissue is discussed and used to predict collagen damage in the aneurysm wall at supra-physiologic loading. The physical meaning of model parameters allow their straight forward identification from independent mechanical and histological experimental data. In contrast, if damage accumulates until the material’s stiffness looses its strong ellipticity, more advanced continuum mechanical approaches are required. Specifically, modeling vascular failure by a fracture process zone is discussed, such that initialization and coalescence of micro-defects is mechanically represented by a phenomenological cohesive traction separation law. Failure of ventricular tissue due to deep penetration illustrates the applicability of the model. Besides appropriate continuum mechanical approaches, laboratory experiments that are sensitive to constitutive model parameters and ensure controlled failure propagation are crucial for a robust parameter identification of failure models. 

  • 3.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    The biomechanical rupture risk assessment of abdominal aortic aneurysms—method and clinical relevance2018In: Lecture Notes in Applied and Computational Mechanics, Springer Verlag , 2018, p. 233-253Conference paper (Refereed)
    Abstract [en]

    An Abdominal Aortic Aneurysm (AAA) is an enlargement of the infrarenal aorta, a serious condition whose clinical treatment requires assessing its risk of rupture. This chapter reviews the current state of the Biomechanical Rupture Risk Assessment (BRRA), a non-invasive diagnostic method to calculate such AAA rupture risk, and emphasizes on constitutive modeling of AAA tissues. Histology and mechanical properties of the normal and aneurysmatic walls are summarized and related to proposed constitutive descriptions. Models for the passive vessel wall as well as their adaptation in time are discussed. Reported clinical BRRA validation studies are summarized and their clinical relevance is discussed. Despite open problems in AAA biomechanics, like robust modeling vascular tissue adaptation to mechanical and biochemical environments, a significant body of current validation evidence suggests integrating the BRRA method into the clinical decision-making process. 

  • 4.
    Grytsan, Andrii
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.). Insigneo Institute for in silico Medicine, University of Sheffield, Sheffield S1 3JD, UK.
    Eriksson, Thomas S. E.
    Watton, Paul N.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Growth Description for Vessel Wall Adaptation: A Thick-Walled Mixture Model of Abdominal Aortic Aneurysm Evolution2017In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 10, no 9, article id 994Article in journal (Refereed)
    Abstract [en]

    (1) Background: Vascular tissue seems to adapt towards stable homeostatic mechanical conditions, however, failure of reaching homeostasis may result in pathologies. Current vascular tissue adaptation models use many ad hoc assumptions, the implications of which are far from being fully understood; (2) Methods: The present study investigates the plausibility of different growth kinematics in modeling Abdominal Aortic Aneurysm (AAA) evolution in time. A structurally motivated constitutive description for the vessel wall is coupled to multi-constituent tissue growth descriptions; Constituent deposition preserved either the constituent's density or its volume, and Isotropic Volume Growth (IVG), in-Plane Volume Growth (PVG), in-Thickness Volume Growth (TVG) and No Volume Growth (NVG) describe the kinematics of the growing vessel wall. The sensitivity of key modeling parameters is explored, and predictions are assessed for their plausibility; (3) Results: AAA development based on TVG and NVG kinematics provided not only quantitatively, but also qualitatively different results compared to IVG and PVG kinematics. Specifically, for IVG and PVG kinematics, increasing collagen mass production accelerated AAA expansion which seems counterintuitive. In addition, TVG and NVG kinematics showed less sensitivity to the initial constituent volume fractions, than predictions based on IVG and PVG; (4) Conclusions: The choice of tissue growth kinematics is of crucial importance when modeling AAA growth. Much more interdisciplinary experimental work is required to develop and validate vascular tissue adaption models, before such models can be of any practical use.

  • 5.
    Hamedzadeh, Amir
    et al.
    Univ Calgary, Grad Programme Mech Engn, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada..
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Federico, Salvatore
    Univ Calgary, Dept Mech & Mfg Engn, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada..
    On the constitutive modelling of recruitment and damage of collagen fibres in soft biological tissues2018In: European journal of mechanics. A, Solids, ISSN 0997-7538, E-ISSN 1873-7285, Vol. 72, p. 483-496Article in journal (Refereed)
    Abstract [en]

    The aim of this work is to propose a recruitment and damage constitutive model for collagen fibres in soft biological tissues. Similarly to other published models, our model employs probability distribution functions in order to capture the progressive recruitment and damage of fibrils in a collagen fibre. We rigorously investigate the continuum mechanical treatment of recruitment and damage using a multiplicative decomposition of the deformation gradient. Our proposed model stems from the correction, generalisation and extension to damage of the recruitment model proposed by Martufi and Gasser (2011, J. Biomech., 44, 2544-2550). We demonstrate that the generalised model is equivalent to the recruitment and damage model proposed by Hurschler et al. (1997, J. Biomech. Eng., 119, 392-399). Finally, we explore the sensitivity of the proposed model to the parameters describing recruitment and damage, implement the model into Finite Elements and show an example of application, which gives good agreement with published experimental data.

  • 6.
    Larsson, David
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering.
    Roy, J.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Urban, M. W.
    Colarieti-Tosti, Massimiliano
    KTH, School of Technology and Health (STH), Medical Engineering.
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering.
    An ex-vivo setup for characterization of atherosclerotic plaque using shear wave elastography and micro-computed tomography2016In: IEEE International Ultrasonics Symposium, IUS, IEEE conference proceedings, 2016, article id 7728810Conference paper (Refereed)
    Abstract [en]

    Quantification of the mechanical properties of atherosclerotic plaque has shown to be important in assessing carotid artery plaque vulnerability. For such, shear wave elastography (SWE) has been applied on both in-vitro and in-vivo setups. The aim of this study was to build an ex-vivo setup for combined evaluation of plaque characteristics using SWE and micro-computed tomography (μCT). As a proof-of-concept of the constructed experimental setup, a single human carotid plaque specimen was extracted during carotid endarterectomy. The plaque was imaged in the μCT system, and subsequently imaged using SWE. For the SWE measurement, group and phase velocity was extracted from the obtained in-phase/quadrature data, with its spatial distribution being compared to anatomical features visible in the μCT images. The results indicated wave velocity changes at boundaries identified in the μCT, with group velocity data slightly increasing when entering a calcified nodule. Additionally, μCT images seemed to provide good contrast between several plaque constituens using the defined imaging settings. Overall, the study represents a proof-of-concept for detailed ex-vivo plaque analysis using combined SWE and μCT, with obtained wave speed and shear modulus values falling within observed values for atherosclerotic plaque tissue. With an experimental setup defined, future studies on carotid plaque behaviour both in SWE and μCT is enabled, where a large-scale plaque study could be performed to investigate the ability of SWE to differentiate between different plaque types.

  • 7. Liljeqvist, Moritz Lindquist
    et al.
    Silveira, Angela
    Hultgren, Rebecka
    Frebelius, Siw
    Lengquist, Mariette
    Engström, Jan
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Eriksson, Per
    Roy, Joy
    Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume2018In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 118, no 2, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Background The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs. Methods E-XDP and D-dimer were measured in plasma from 37 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 29 patients and finite element analysis was performed to estimate mechanical stress of the ILT. E-XDP, neutrophil elastase and neutrophil marker CD66acd were evaluated in aortic tissue with immunohistochemistry (IHC). The association between ILT volume and E-XDP was validated in a separate cohort (n = 51). Results E-XDP levels were elevated in patients with AAA compared with controls (p = 5.8e-13), indicated AAA with 98% sensitivity, 86% specificity and increased with presence of coexisting aneurysms. The association between AAA and increased E-XDP was independent of smoking, comorbidities and medication. E-XDP correlated with volume of all ILTs (r = 0.76, p = 4.5e-06), mean ILTstress (r = 0.46, p = 0.013) and the volume of the AAA-associated ILT (r = 0.64, p = 0.00017). E-XDP correlated stronger with ILT volume compared with D-dimer (r = 0.76 vs. r = 0.64, p = 0.018). The correlation between E-XDP and ILT volume was validated in the separate cohort (r = 0.53, p = 7.6e-05). IHC revealed E-XDP expression in the ILT, spatially related to neutrophil elastase and neutrophils. Conclusion E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.

  • 8. Rowbotham, S. E.
    et al.
    Pinchbeck, J. L.
    Anderson, G.
    Bourke, B.
    Bourke, M.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Jaeggi, R.
    Jenkins, J. S.
    Moran, C. S.
    Morton, S. K.
    Reid, C. M.
    Velu, R.
    Yip, L.
    Moxon, J. V.
    Golledge, J.
    Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN): Study protocol for a randomised controlled trial2017In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 18, no 1, article id 547Article in journal (Refereed)
    Abstract [en]

    Background: An abdominal aortic aneurysm (AAA) is a focal dilation of the abdominal aorta and is associated with a risk of fatal rupture. Experimental studies suggest that myo-inositol may exert beneficial effects on AAAs through favourable changes to biological pathways implicated in AAA pathology. The aim of the Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN) trial is to assess if myo-inositol will reduce AAA growth. Methods/design: IMAGEN is a multi-centre, prospective, parallel-group, randomised, double-blind, placebo-controlled trial. A total of 164 participants with an AAA measuring ≥ 30 mm will be randomised to either 2 g of myo-inositol or identical placebo twice daily for 12 months. The primary outcome measure will be AAA growth estimated by increase in total infrarenal aortic volume measured on computed tomographic scans. Secondary outcome measures will include AAA diameter assessed by computed tomography and ultrasound, AAA peak wall stress and peak wall rupture index, serum lipids, circulating AAA biomarkers, circulating RNAs and health-related quality of life. All analysis will be based on the intention-to-treat principle at the time of randomisation. All patients who meet the eligibility criteria, provide written informed consent and are enrolled in the study will be included in the primary analysis, regardless of adherence to dietary allocation. Discussion: Currently, there is no known medical therapy to limit AAA progression. The IMAGEN trial will be the first randomised trial, to our knowledge, to assess the value of myo-inositol in limiting AAA growth.

  • 9.
    Siika, Antti
    et al.
    Karolinska Inst, Dept Mol Med & Surg, L8 03 Karolinska Sjukhuset Solna, S-17164 Stockholm, Sweden..
    Liljeqvist, Moritz Lindquist
    Karolinska Inst, Dept Mol Med & Surg, L8 03 Karolinska Sjukhuset Solna, S-17164 Stockholm, Sweden..
    Hultgren, Rebecka
    Karolinska Inst, Dept Mol Med & Surg, L8 03 Karolinska Sjukhuset Solna, S-17164 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden..
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Roy, Joy
    Karolinska Inst, Dept Mol Med & Surg, L8 03 Karolinska Sjukhuset Solna, S-17164 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden..
    Aortic Lumen Area Is Increased in Ruptured Abdominal Aortic Aneurysms and Correlates to Biomechanical Rupture Risk2018In: Journal of Endovascular Therapy, ISSN 1526-6028, E-ISSN 1545-1550, Vol. 25, no 6, p. 750-756Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate how 2-dimensional geometric parameters differ between ruptured and asymptomatic abdominal aortic aneurysms (AAAs) and provide a biomechanical explanation for the findings. Methods: The computed tomography angiography (CTA) scans of 30 patients (mean age 77 +/- 10 years; 23 men) with ruptured AAAs and 60 patients (mean age 76 +/- 8 years; 46 men) with asymptomatic AAAs were used to measure maximum sac diameter along the center lumen line, the cross-sectional lumen area, the total vessel area, the intraluminal thrombus (ILT) area, and corresponding volumes. The CTA data were segmented to create 3-dimensional patient-specific models for finite element analysis to compute peak wall stress (PWS) and the peak wall rupture index (PWRI). To reduce confounding from the maximum diameter, 2 diameter-matched groups were selected from the initial patient cohorts: 28 ruptured AAAs and another with 15 intact AAAs (diameters 74 +/- 12 vs 73 +/- 11, p=0.67). A multivariate model including the maximum diameter, the lumen area, and the ILT area of the 60 intact aneurysms was employed to predict biomechanical rupture risk parameters. Results: In the diameter-matched subgroup comparison, ruptured AAAs had a significantly larger cross-sectional lumen area (1954 +/- 1254 vs 1120 +/- 623 mm(2), p=0.023) and lower ILT area ratio (55 +/- 24 vs 68 +/- 24, p=0.037). The ILT area (2836 +/- 1462 vs 2385 +/- 1364 mm(2), p=0.282) and the total vessel area (3956 +/- 1170 vs 4338 +/- 1388 mm(2), p=0.384) did not differ statistically between ruptured and intact aneurysms. The PWRI was increased in ruptured AAAs (0.80 vs 0.48, p<0.001), but the PWS was similar (249 vs 284 kPa, p=0.194). In multivariate regression analysis, lumen area was significantly positively associated with both PWS (p<0.001) and PWRI (p<0.01). The ILT area was also significantly positively associated with PWS (p<0.001) but only weakly with PWRI (p<0.01). The lumen area conferred a higher risk increase in both PWS and PWRI when compared with the ILT area. Conclusion: The lumen area is increased in ruptured AAAs compared to diameter-matched asymptomatic AAAs. Furthermore, this finding may in part be explained by a relationship with biomechanical rupture risk parameters, in which lumen area, irrespective of maximum diameter, increases PWS and PWRI. These observations thus suggest a possible method to improve prediction of rupture risk in AAAs by measuring the lumen area without the use of computational modeling.

  • 10.
    Siika, Antti
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Liljeqvist, Moritz Lindquist
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Zommorodi, Sayid
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Reconstruct Plast Surg, Stockholm, Sweden..
    Nilsson, Olga
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Andersson, Patricia
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Roy, Joy
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden..
    Hultgren, Rebecka
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden..
    A large proportion of patients with small ruptured abdominal aortic aneurysms are women and have chronic obstructive pulmonary disease2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0216558Article in journal (Refereed)
    Abstract [en]

    Objective In a population-based cohort of ruptured abdominal aortic aneurysms (rAAAs), our aim was to investigate clinical, morphological and biomechanical features in patients with small rAAAs. Methods All patients admitted to an emergency department in Stockholm and Gotland, a region with a population of 2.1 million, between 2009-2013 with a CT-verified rupture (n = 192) were included, and morphological measurements were performed. Patients with small rAAAs, maximal diameter (Dmax) <= 60 mm were selected (n = 27), and matched 2: 1 by Dmax, sex and age to intact AAA (iAAAs). For these patients, morphology including volume and finite element analysis-derived biomechanics were assessed. Results The mean Dmax for all rAAAs was 80.8 mm (SD = 18.9 mm), women had smaller Dmax at rupture (73.4 +/- 18.4 mm vs 83.1 +/- 18.5 mm, p = 0.003), and smaller neck and iliac diameters compared to men. Aortic size index (ASI) was similar between men and women (4.1 +/- 3.1 cm/m(2) vs 3.8 +/- 1.0 cm/m(2)). Fourteen percent of all patients ruptured at Dmax <= 60 mm, and a higher proportion of women compared to men ruptured at Dmax <= 60 mm: 27% (12/45) vs. 10% (15/147), p = 0.005. Also, a higher proportion of patients with a chronic obstructive pulmonary disease ruptured at Dmax <= 60 mm (34.6% vs 14.6%, p = 0.026). Supra-renal aortic size index (14.0, IQR 13.3-15.3 vs 12.8, IQR = 11.4-14.0) and peak wall rupture index (PWRI, 0.35 +/- 0.08 vs 0.43 +/- 0.11, p = 0.016) were higher for small rAAAs compared to matched iAAAs. Aortic size index, peak wall stress and aneurysm volume did not differ. Conclusion More than one tenth of ruptures occur at smaller diameters, women continuously suffer an even higher risk of presenting with smaller diameters, and this must be considered in surveillance programs. The increased supra-renal aortic size index and PWRI are potential markers for rupture risk, and patients under surveillance with these markers may benefit from increased attention, and potentially from timely repair.

  • 11. Singh, T. P.
    et al.
    Wong, S. A.
    Moxon, J. V.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Golledge, J.
    Systematic review and meta-analysis of the association between intraluminal thrombus volume and abdominal aortic aneurysm rupture2019In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809Article in journal (Refereed)
    Abstract [en]

    Background: Intraluminal thrombus (ILT) is present in most abdominal aortic aneurysms (AAAs), although its role in AAA progression is controversial. Methods: A literature search was performed to identify studies that investigated the association between ILT volume and AAA rupture. A study assessment tool was developed to assess the methodologic quality of included studies. A meta-analysis was conducted using an inverse variance-weighted random-effects model to compare the ILT volume in ruptured and asymptomatic intact AAAs. Leave-one-out sensitivity analyses were conducted to assess the robustness of the findings. A subanalysis was performed including studies in which patients with asymptomatic intact and ruptured AAAs were matched for aortic diameter. Interstudy heterogeneity was assessed using the I2 statistic. Results: Eight studies involving 672 patients were included in this systematic review. Meta-analysis of all studies found a greater ILT volume in patients with ruptured AAAs than in patients with asymptomatic intact AAAs (standardized mean difference, 0.56; 95% confidence interval, 0.17-0.96; P =.005; I2 = 79.8%). Sensitivity analyses suggested that the findings were robust; however, aortic diameter was significantly larger in ruptured than in asymptomatic intact AAAs (mean ± standard deviation, 78 ± 18 and 64 ± 15 mm, respectively; P &lt;.001). In the subanalysis of studies that matched for diameter, no significant difference in ILT volume between groups was found (standardized mean difference, 0.03; 95% confidence interval, −0.27 to 0.33; P =.824; I2 = 0%). Conclusions: This meta-analysis suggests that ILT volume is greater in patients with ruptured AAAs than in patients with asymptomatic intact AAAs, although this is most likely due to the larger diameter of ruptured AAAs.

  • 12.
    Stevens, Raoul
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Solid Mechanics (Div.).
    Grytsan, Andrii
    Biasetti, Jacopo
    Roy, Joy
    Liljeqvist, Moritz Lindquist
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Biomechanical changes during abdominal aortic aneurysm growth2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0187421Article in journal (Refereed)
    Abstract [en]

    The biomechanics-based Abdominal Aortic Aneurysm (AAA) rupture risk assessment has gained considerable scientific and clinical momentum. However, such studies have mainly focused on information at a single time point, and little is known about how AAA properties change over time. Consequently, the present study explored how geometry, wall stress-related and blood flow-related biomechanical properties change during AAA expansion. Four patients with a total of 23 Computed Tomography-Angiography (CT-A) scans at different time points were analyzed. At each time point, patient-specific properties were extracted from (i) the reconstructed geometry, (ii) the computed wall stress at Mean Arterial Pressure (MAP), and (iii) the computed blood flow velocity at standardized inflow and outflow conditions. Testing correlations between these parameters identified several nonintuitive dependencies. Most interestingly, the Peak Wall Rupture Index (PWRI) and the maximum Wall Shear Stress (WSS) independently predicted AAA volume growth. Similarly, Intra-luminal Thrombus (ILT) volume growth depended on both the maximum WSS and the ILT volume itself. In addition, ILT volume, ILT volume growth, and maximum ILT layer thickness correlated with PWRI as well as AAA volume growth. Consequently, a large ILT volume as well as fast increase of ILT volume over time may be a risk factor for AAA rupture. However, tailored clinical studies would be required to test this hypothesis and to clarify whether monitoring ILT development has any clinical benefit.

  • 13. Terzian, Z.
    et al.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Blackwell, F.
    Hyafil, F.
    Louedec, L.
    Ghodbane, W.
    Dorent, R.
    Nicoletti, A.
    Morvan, M.
    Nejjari, M.
    Feldman, L.
    Pavon-Djavid, G.
    Michel, B.
    Peri-strut red blood cell release: the cause of in-stent neoatherothrombosis?2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 789-789Article in journal (Refereed)
  • 14. Terzian, Zaven
    et al.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Blackwell, Francis
    Hyafil, Fabien
    Louedec, Liliane
    Deschildre, Catherine
    Ghodbane, Walid
    Dorent, Richard
    Nicoletti, Antonino
    Morvan, Marion
    Nejjari, Mohammed
    Feldman, Laurent
    Pavon-Djavid, Graciela
    Michel, Jean-Baptiste
    Peristrut microhemorrhages: a possible cause of in-stent neoatherosclerosis?2017In: Cardiovascular pathology, ISSN 1054-8807, E-ISSN 1879-1336, Vol. 26, no 1, p. 30-38Article in journal (Refereed)
    Abstract [en]

    Background: In-stent neoatherosclerosis is characterized by the delayed appearance of markers of atheroma in the subintima, but the pathophysiology underlying this new disease entity remains unclear. Methods and results: We collected 20 human coronary artery stents by removal from explanted hearts. The mean duration of stent implantation was 34 months. In all samples, neoatherosclerosis was detected, particularly in peristrut areas. It consisted of foam cells and cholesterol clefts, with or without calcification, associated with neovascularization. Iron and glycophorin-A were present in peristrut areas, as well as autofluorescent ceroids. Moreover, in response to neoatherosclerosis, tertiary lymphoid organs (tissue lymphoid clusters) often developed in the adventitia. Some of these features could be reproduced in an experimental carotid stenting model in rabbits fed a high-cholesterol diet. Foam cells were present in all samples, and peristrut red blood cells (RBCs) were also detected, as shown by iron deposits and Bandeiraea simplicifiola isolectin-B4 staining of RBC membranes. Finally, in silico models were used to evaluate the compliance mismatch between the rigid struts and the distensible arterial wall using finite element analysis. They show that stenting approximately doubles the local von Mises stress in the intimal layer. Conclusions: We show here that stent implantation both in human and in rabbit arteries is characterized by local peristrut microhemorrhages and finally by both cholesterol accumulation and oxidation, triggering together instent neoatherosclerosis. Our data indicate that these processes are likely initiated by an increased mechanical stress due to the compliance mismatch between the rigid stent and the soft wall. (C) 2016 The Authors. Published by Elsevier Inc.

  • 15.
    Xie, Meng
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Gol'din, Pavel
    Stockholm Univ, Stockholm, Sweden..
    Estsfa, Jordi
    Uppsala Univ, Dept Organismal Biol, Uppsala, Sweden..
    Li, Lei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Linares Arregui, Irene
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Medvedeva, Ekaterina
    Sechenov Med Univ, Moscow, Russia..
    Svetlana, Kotova
    Sechenov Med Univ, Moscow, Russia..
    Timashev, Peter
    Sechenov Med Univ, Moscow, Russia..
    Adameyko, Igor
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Eriksson, Anders
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Sanchez, Sophie
    Uppsala Univ, Dept Organismal Biol, Uppsala, Sweden..
    Chagin, Andrei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Evolutional Separation of Epiphyseal and Articular Cartilage is a Bone Adaptation to Terrestrial Growth2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, p. S328-S328Article in journal (Other academic)
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