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In this study, we analysed the influence of atherosclerosis on the anisotropic and incompressible behaviour of the human thoracic aortic wall under mechanical loads. The mechanical tests involved preparations of the human thoracic aortic wall, which were evaluated based on the six-stage histological classification of atherosclerosis proposed by Stary. Anisotropy was evaluated on the basis of directional tests of mechanical properties, which were determined based on a uniaxial tensile test conducted in two directions, i.e. longitudinal and circumferential. The evaluation of incompressibility was carried out based on the product of the stretch ratios obtained in the x–y and y–z planes and on the basis of Poisson’s ratio. The results presented in this study indicate that the blood vessel wall is an anisotropic material only in the case of normal vessels and in early atherosclerotic lesions. Atherosclerosis progression causes a gradual loss of the anisotropic character of the work of the thoracic aortic wall in moderate and very advanced stages of atherosclerosis under mechanical loads. The results show that the wall of the thoracic aorta is an incompressible material. Development of atherosclerosis does not cause a loss of incompressibility of the thoracic aorta. This study is the only one so far that presents changes in the mechanical properties at all stages of atherosclerotic development. A large number of preparations were included in the study, which is important for the results obtained due to the multi-factorial etiology of atherosclerosis development.

Wall shear stress (WSS) plays a governing role in vascular remodeling and a pathogenic role in vessel wall diseases. However, little is known of the normal WSS patterns in the aorta as there is currently no practical means to routinely measure WSS and no normal ranges derived from population data exist. WSS measurements were made on the aorta of 224 subjects with normal anatomy using four-dimensional flow MRI with multiple encoding velocities and an optimized postprocessing routine. The spatial and temporal variation in WSS and oscillatory shear index was analyzed using a flat map representation of the unfolded aorta. The influence of aortic shape and velocity on WSS was evaluated using regression analysis. WSS in the thoracic aorta is dominated by axial flow. Average peak systolic WSS was 1.79 ± 0.71 Pa in the aortic arch and was significantly higher at 2.23 ± 1.04 Pa in the descending aorta, with a strong negative correlation with advancing age. The spatial distribution of WSS is highly heterogeneous, with a localized region of elevated WSS along the length of the anterior wall seen across all individuals. Our data demonstrate that accurate four-dimensional flow-derived WSS measurement is feasible, and we further provide a standardized parametric approach for presentation and analysis. We present a normal range for WSS across the lifespan, demonstrating a decrease in WSS with advancing age as well as illustrating the high degree of spatial and temporal variation. NEW & NOTEWORTHY With the use of four-dimensional flow MRI and postprocessing, accurate direct measurement of wall shear stress (WSS) was performed in a population of normal thoracic aortas ( n = 224). WSS was higher in the descending aorta compared with the aortic arch and decreased with age. A heterogeneous pattern of elevated WSS along the length of the aorta anterior wall was consistent across the population. This work provides normal data across the adult age range, permitting comparison with pathology.

The aim of the study was to evaluate the mechanical properties of the adventitia, media, and especially intima of the human thoracic aortic wall in the early stages of atherosclerosis (stage I to III according to the Stary's classification). Histological and immunohistochemical techniques were used to evaluate the severity of atherosclerosis and the correctness of separation of the respective layers. Circumferential specimens of the adventitia, media, and intima ( n = 193) were prepared from 27 arteries. The mechanical properties, i.e. the ultimate tensile strength, the maximum strain, and the maximum tangential elastic moduli, were determined in uniaxial tensile test and presented as a median (Me). The tensile strength of the intima (Me = 105 kPa) is comparable to the media (Me = 123 kPa) and lower than for the adventitia (Me = 808.5 kPa). The intima also undergoes the lowest maximum strain (Me = 0.008), and its elastic modulus (Me = 11510 kPa) is significantly higher compared to the media (Me = 5280 kPa). Therefore, presented results indicate that even in the early stages of atherosclerotic development the intima takes part in the process of mechanical loads bearing.

The study of the mechanical processes that occur within the aorta—both healthy and diseased—from an engineering perspective is rapidly progressing. Understanding the exact biomechanical processes that underlie aortic disease, such as aortic aneurysm, dissection, and rupture, is a critical supplement to clinical studies of the natural history of these diseases. Engineering analysis promises to enhance management and timing of surgical intervention. In this chapter we discuss the current understanding of the mechanics of the thoracic aorta and thoracic aortic aneurysm based on in vivo and ex vivo studies. We address also the clinical application of engineering insights and their significance for surgical decision-making.

The aim of this work is to determine mechanical properties of interfaces between layers of the human thoracic aortic wall with early stages of atherosclerosis lesions. Circumferential (n = 48) and axial (n = 15) specimens have been prepared and the mechanical properties of the interfaces between the layers have been determined on the basis of the peeling test. The results show that the mechanical and dissection properties of the interfaces between the layers depend on the direction of the tests. The results confirm that the early stage of atherosclerosis does not affect the mechanical parameters of the layer interfaces and does not affect resistance of the vessel wall to delamination.

The aim of this work is to determine the impact of development of atherosclerosis on dissection of the human thoracic aorta on the basis of an analysis of the mechanical properties of the interfaces between its layers. The research material consisted of 17 pathologically unchanged aortae and 74 blood vessels with atherosclerotic lesions, which were classified according to the histological classification by Stary. The subject of the analysis were the interfaces between the adventitia and the media-intima complex (A-MIC) and between the intima and the media-adventitia complex (I-MAC). The mechanical properties of the above interfaces were determined by the peeling test in the longitudinal and circumferential directions. The results indicate that development of atherosclerosis reduces vessel wall resistance to delamination. The greatest risk of dissection occurs at stage IV of the disease. In this case, energy values are lower by about 28% for the I-MAC interface and by 39% for the A-MIC interface compared with normal tissues. Lower values of mean force and energy were obtained for the I-MAC interface, indicating that this interface is more susceptible to delamination. The mechanical properties of the A-MIC interfaces are directional.

Objectives Syphilis infection persists globally contributing to preventable and treatable morbidity and mortality. How extensive early syphilis disseminates is unknown. To better understand the relationship between early syphilis infection and inflammation over time, our study enrolled six individuals recently infected with syphilis for sequential positron emission tomography (PET) scans. Methods We evaluated a case series of six individuals with high syphilis titres (two secondary, two early latent and two latent, unknown duration, but with high titre) who received sequential PET scans to assess inflammation over time and its response to treatment. Results At time of PET scan, four of the six individuals were co-infected with HIV. One of the four was not on antiretroviral therapy and three of the four were not virally suppressed (viral load of >400 copies/mL). Baseline rapid plasma reagin (RPR) titres ranged from 1:64 to 1:256 (four of the six participants had prior non-reactive RPR results). Five of the six participants had mild to intense hypermetabolic PET scan activity consistent with cervical (n=5), axillary (n=4), inguinal (n=5) and retroperitoneal (n=1) adenopathy. Mild hypermetabolic activity in the thoracic aortic wall, suggesting aortitis, was present among the same five participants and resolved within 30 days for four of the five participants and 60 days for the other participant. However, widespread lymphadenopathy remained present in PET scans up to 3 months following treatment in two participants. We did not find any abnormal PET scan activity of the central nervous system. Conclusion We found abnormal aortic wall PET scan activity suggesting aortitis to be common in a case series of patients with early syphilis. In research settings, PET scans may be a sensitive tool to monitor inflammation associated with syphilis.

Q fever is a zoonosis caused by the rickettsial organism Coxiella burnetii. Infection has an acute course, usually with a self-limited febrile illness and the possibility of the evaluation to a chronic course with endocardial involvement. The presence of autoantibodies and various autoimmune disorders have also been associated with C. burnetii infection. We report a case of acute Q fever in which the patient developed large vessel vasculitis. The FDG-PET/CT scan detected inflammation of the thoracic aortic wall, suggesting an unusual immunologic host response to acute Q fever infection.

Background: MicroRNA-133a (miR133a) is a small non-coding RNA, which represses the translation of multiple mRNAs. This laboratory has reported an inverse relationship between aortic diameter and miR133a abundance in aortic tissue from patients with thoracic aortic aneurysm (TAA); as diameter increased, the abundance of miR133a decreased. Given that wall tension at a given pressure increases with increasing vessel diameter (Law of LaPlace), this study tested the hypothesis that elevated aortic wall tension results in a loss of miR-133a. Methods/Results: TAA was induced in wild type mice using an established murine model (0.5M CaCl 2 application, 15 min). MiR133a abundance (QPCR) was reduced in TAA tissue (3-wk TAA, 42.1±8.6% pin vivo models of elevated wall tension ( simulated hypertension ): 1) ANGII (angiotensin II infusion; 1.44mg/kg/day), and 2) BPH2 (spontaneously hypertensive mice, The Jackson Laboratory, Stock #003005), miR133a levels were decreased compared to normotensive controls (ANGII: 53.0±4.3%; BPH2: 51.7±7.0%; pex vivo tissue myograph at 0.7 g, then ANGII (100nM) was added to the tissue baths, which generated increased tension (1.21±0.15g) and resulted in reduced tissue miR133a abundance (46.0±12%; p Conclusion: The significance of these unique findings is 2-fold: First, tension alone was sufficient to decrease miR133a abundance in aortic tissue. Second, increased tension reduced miR133a abundance in FB, a cell type that is responsible for extracellular matrix remodeling. These findings suggest changes in wall tension alone ( hypertension ) may be associated with pathological extracellular matrix remodeling, in part, through the loss of miR133a in fibroblasts.

This work developed a three-dimensional (3D) diffusion-prepared segmented steady-steady free precession (DP-SSFP) cardiovascular magnetic resonance (CMR) sequence for black-blood (BB) thoracic aortic and carotid wall visualization. In 14 healthy volunteers, BB CMR of the thoracic aorta (n = 7) and carotid arteries (n = 7) was performed over 12 cm and 3 cm of transversal coverage, respectively, with a single 3D DP-SSFP acquisition and multiple two-dimensional (2D) slices using a T2-weighted (T2W) double inversion-recovery fast spin-echo (DIR-FSE) sequence. Arterial wall area (WA), lumen area (LA), and wall-lumen contrast-to-noise ratio (CNR) measured from the 3D DP-SSFP images were compared to those measured from the 2D T2W DIR-FSE images. Strong agreement in WA and LA between the two techniques was observed in the thoracic aorta (WA: intraclass correlation coefficient (ICC) = 0.866, LA: ICC = 0.993; p < 0.001 for both) and carotid arteries (WA: ICC = 0.939, LA: ICC = 0.991; p < 0.001 for both). Adjusted for slice thickness and number of slices, higher effective CNR per unit time (i.e., CNR efficiency) was attained with 3D DP-SSFP than 2D T2W DIR-FSE during thoracic aortic wall imaging (11.6 +/- 1.4 vs. 2.9 +/- 0.5; p < 0.001) and carotid artery wall imaging (10.1 +/- 1.9 vs. 3.1 +/- 0.5; p < 0.001). Diffusion-prepared segmented SSFP is a promising vessel wall CMR sequence that allows for 3D acquisition of thin and contiguous slices with BB image contrast.

The thoracic aortic wall is a common site of atherosclerotic plaque in humans. Tools for serial, non-invasive assessment of these plaques are of value for addressing gaps in our basic understanding of the biology of plaque rupture and its relationship to atherosclerotic disease progression as well as for monitoring response to anti-atherosclerotic interventions in therapeutic clinical trials. Common approaches to assessment of the wall of the thoracic aorta in vivo are limited. Here we discuss some of the challenges and limitations encountered by conventional techniques and review a novel approach, transesophageal MRI (TEMRI). Initial experiences in applying the TEMRI approach to assessment of aortic morphology and pathology are discussed.

Background —The structure and composition of aortic atherosclerotic plaques are associated with the risk of future cardiovascular events. Magnetic resonance (MR) imaging may allow accurate visualization and characterization of aortic plaques. Methods and Results —We developed a noninvasive MR method, free of motion and blood flow artifacts, for submillimeter imaging of the thoracic aortic wall. MR imaging was performed on a clinical MR system in 10 patients with aortic plaques identified by transesophageal echocardiography (TEE). Plaque composition, extent, and size were assessed from T1-, proton density–, and T2- weighted images. Comparison of 25 matched MR and TEE cross-sectional aortic plaque images showed a strong correlation for plaque composition (χ 2 =43.5, P r =0.88, n=25; 4.56±0.21 mm by MR and 4.62±0.31 mm by TEE). Overall aortic plaque extent as assessed by TEE and MR was also statistically significant (χ 2 =61.77, P Conclusions —This study demonstrates that noninvasive MR evaluation of the aorta compares well with TEE imaging for the assessment of atherosclerotic plaque thickness, extent, and composition. This MR method may prove useful for the in vivo study of aortic atherosclerosis.

To provide age- and sex-specific reference values for MRI-derived wall thickness of the ascending and descending aorta in the general population. Data of 753 subjects (311 females) aged 21-81 years were analysed. MRI was used to determine the aortic wall thickness (AWT). Equations for reference value calculation according to age were established for females and males. Median wall thickness of the ascending aorta was 1.46 mm (5th–95th range: 1.15–1.88 mm) for females and 1.56 mm (1.22-1.99 mm) for males. Median wall thickness of the descending aorta was 1.26 mm (0.97-1.58 mm) in females and 1.36 mm (1.04-1.75 mm) in males. While median and 5th and 95th percentiles for the ascending and descending aorta increased with age in both sexes, the association between age and median AWT was stronger in males than in females for both the ascending and descending aorta. Reference values for the ascending and descending AWT are provided. In a healthy sample from the general population, the wall of the ascending aorta is thicker than the wall of the descending aorta, and both walls are thicker in males than females. The increase in wall thickness with age is greater in males. • Ascending aortic wall thickness is greater than descending aortic wall thickness. • Ascending and descending aortic wall thickness is greater in males. • Thoracic aortic wall thickness increases with age in both sexes. • The age-related increase in aortic wall thickness is stronger in males.

The effect of a strong, lipophilic statin (pitavastatin) on the thoracic aorta has not yet been elucidated. The purpose of the present study was to evaluate the effects of pitavastatin (P) therapy on plaque components and morphology in the thoracic aorta by transesophageal echocardiography (TEE) and clarify the impact of the therapy on media and intima in patients with hypercholesterolemia. Sixty-four media and 64 intima of the thoracic aorta were investigated in 32 patients with hypercholesterolemia. The corrected integrated backscatter (c-IBS) values in the thoracic aortic wall and intima-media thickness (IMT) at the same site were measured before and after P therapy or diet (D) for 7 mo. Moreover, c-IBS values in media were measured in 168 patients without hypercholesterolemia to estimate age-dependent changes. C-IBS values in media were correlated with age (r = 0.84, p0.001). C-IBS and IMT of media in the P group significantly decreased from -17.8 +/- 2.4 to -20.1 +/- 3.7 dB and from 1.7 +/- 0.3 to 1.5 +/- 0.3 mm, respectively (p0.001), whereas those in the D group significantly increased from -18.3 +/- 2.0 to -16.7 +/- 2.1 dB and from 1.6 +/- 0.3 to 1.7 +/- 0.2 mm, respectively (p0.001). IMT in intima in the P group significantly decreased from 3.7 +/- 0.4 to 3.3 +/- 0.4 mm (p0.001). C-IBS in intima in the P group significantly increased from -10.2 +/- 2.2 to -6.9 +/- 1.7 dB, which indicated plaque stabilization. Pitavastatin improved the atherosis measured by IMT and sclerosis measured by c-IBS values in the media and induced stabilization and regression of plaques in the intima of the thoracic aorta.

Background Wall shear stress (WSS) may be associated with the onset and development of aortopathy in the presence of bicuspid aortic valve (BAV) [Michelena, JAMA (2011)]. The use of ‘aortic atlases’ of 3D WSS vectors allows for systematic analysis of WSS differences between large patient cohorts. In this study, a comparison is performed between WSS atlases of BAV patients, BAV patients with aortic dilation, patients with BAV stenosis, and healthy controls with tricuspid valves. The aim is to test the hypothesis that WSS atlases can identify regions of significantly altered WSS that are associated with different expression of BAV and aortopathy.

Background Previously, we have shown that increased visceral adiposity was an independent predictor of thoracic aortic wall thickness in elderly individuals at risk for future cardiovascular (CV) events. In this study, we sought to assess the influence of obesity on rest and stress induced changes in aortic stiffness in older individuals with hypertension, diabetes or coronary artery disease at risk for future CV events.

The paper deals with an analytical study on the stability of blood vessel walls. The theory of small deformation superposed on a known state of finite deformation, together with the anisotropic visco-elastic constitutive relations of Vaishnav and Patel [1] for vascular tissues, are employed for the purpose. By using the material functions of Young et al. [2], the latent instabilities of canine middle descending thoracic aortic wall are predicted in terms of the circumferential and axial extension ratios.

Strips of human thoracic aortic wall taken at autopsy from 23 individuals aged 15–81 years have been tested in two ways: in uniaxial loading and by digestion in 0.1 M NaOH at 75 °C under a load of 50 g. The circumferentially oriented strips were more extensible in loading and took a longer time to fail while being digested under load than the longitudinal strips from the same location. The stress versus strain curve was fitted to an exponential equation of the form, stress = A[exp(B strain)]. For circumferentially oriented strips from 19 subjects, parameter A was independent of age. Parameter B increased by a factor of 2.75 from 19 to 81 years. For longitudinally oriented strips for 14 subjects, A was also independent of age and B increased by 2.4 times from 25 to 81. With digestion under load for 11 matched pairs of strips aged from 32 to 75 the circumferential strips failed in 117 ± 23 min (standard error), while the longitudinal ones failed in 20.3 ± 3.2 min (standard error) (p < 0.003). The results have important implications for vessel attachments to the aorta in heart transplantation and in vascular surgery.Key words: aorta, aging, anisotropy, modulus of elasticity, connective tissue mechanics, elastin–collagen, stress–strain.

We developed a method for absolute quantitative autoradiographic measurement of very low concentrations of [125I]-labeled proteins in arterial tissue using Kodak NTB-2 nuclear emulsion. A precise linear relationship between measured silver grain density and isotope concentration was obtained with uniformly labeled standard sources composed of epoxy-embedded gelatin containing glutaraldehyde-fixed [125I]-albumin. For up to 308-day exposures of 1 micron-thick tissue sections, background grain densities ranged from about two to eight grains/1000 micron 2, and the technique was sensitive to as little as about one grain/1000 micron 2 above background, which correspond to a radioactivity concentration of about 2 x 10(4) cpm/ml. A detailed statistical analysis of variability was performed and the sum of all sources of variation quantified. The half distance for spatial resolution was 1.7 micron. Both visual and automated techniques were employed for quantitative grain density analysis. The method was illustrated by measurement of in vivo transmural [125I]-low-density lipoprotein [( 125I]-LDL) concentration profiles in de-endothelialized rabbit thoracic aortic wall.