An inverse fitting strategy to determine the constrained mixture model parameters: application in patient-specific aorta.

The Constrained Mixture Model (CMM) is a novel approach to describe arterial wall mechanics, whose formulation is based on a referential physiological state. The CMM considers the arterial wall as a mixture of load-bearing constituents, each of them with characteristic mass fraction, material properties, and deposition stretch levels from its stress-free state to the in-vivo configuration. Although some reports of this model successfully assess its capabilities, they barely explore experimental approaches to model patient-specific scenarios. In this sense, we propose an iterative fitting procedure of numerical-experimental nature to determine material parameters and deposition stretch values. To this end, the model has been implemented in a finite element framework, and it is calibrated using reported experimental data of descending thoracic aorta. The main results obtained from the proposed procedure consist of a set of material parameters for each constituent. Moreover, a relationship between deposition stretches and residual strain measurements (opening angle and axial stretch) has been numerically proved, establishing a strong consistency between the model and experimental data.

Arterial wall thickening normalizes arterial wall tension with growth in American alligators, Alligator mississippiensis.

Arterial wall tension increases with luminal radius and arterial pressure. Hence, as body mass (Mb) increases, associated increases in radius induces larger tension. Thus, it could be predicted that high tension would increase the potential for rupture of the arterial wall. Studies on mammals have focused on systemic arteries and have shown that arterial wall thickness increases with Mb and normalizes tension. Reptiles are good models to study scaling because some species exhibit large body size range associated with growth, thus, allowing for ontogenetic comparisons. We used post hatch American alligators, Alligator mississippiensis, ranging from 0.12 to 6.80 kg (~ 60-fold) to investigate how both the right aortic arch (RAo) and the left pulmonary artery (LPA) change with Mb. We tested two possibilities: (i) wall thickness increases with Mb and normalizes wall tension, such that stress (stress = tension/thickness) remains unchanged; (ii) collagen content scales with Mb and increases arterial strength. We measured heart rate and systolic and mean pressures from both systemic and pulmonary circulations in anesthetized animals. Once stabilized alligators were injected with adrenaline to induce a physiologically relevant increase in pressure. Heart rate decreased and systemic pressures increased with Mb; pulmonary pressures remained unchanged. Both the RAo and LPA were fixed under physiological hydrostatic pressures and displayed larger radius, wall tension and thickness as Mb increased, thus, stress was independent from Mb; relative collagen content was unchanged. We conclude that increased wall thickness normalizes tension and reduces the chances of arterial walls rupturing in large alligators.

Behavior of Metalloproteinases in Adipose Tissue, Liver and Arterial Wall: An Update of Extracellular Matrix Remodeling.

Extracellular matrix (ECM) remodeling is required for many physiological and pathological processes. Metalloproteinases (MMPs) are endopeptidases which are able to degrade different components of the ECM and nucleus matrix and to cleave numerous non-ECM proteins. Among pathological processes, MMPs are involved in adipose tissue expansion, liver fibrosis, and atherosclerotic plaque development and vulnerability. The expression and the activity of these enzymes are regulated by different hormones and growth factors, such as insulin, leptin, and adiponectin. The controversial results reported up to this moment regarding MMPs behavior in ECM biology could be consequence of the different expression patterns among species and the stage of the studied pathology. The aim of the present review was to update the knowledge of the role of MMPs and its inhibitors in ECM remodeling in high incidence pathologies such as obesity, liver fibrosis, and cardiovascular disease.

Mechanical Characterization of the Vessel Wall by Data Assimilation of Intravascular Ultrasound Studies.

Atherosclerotic plaque rupture and erosion are the most important mechanisms underlying the sudden plaque growth, responsible for acute coronary syndromes and even fatal cardiac events. Advances in the understanding of the culprit plaque structure and composition are already reported in the literature, however, there is still much work to be done toward in-vivo plaque visualization and mechanical characterization to assess plaque stability, patient risk, diagnosis and treatment prognosis. In this work, a methodology for the mechanical characterization of the vessel wall plaque and tissues is proposed based on the combination of intravascular ultrasound (IVUS) imaging processing, data assimilation and continuum mechanics models within a high performance computing (HPC) environment. Initially, the IVUS study is gated to obtain volumes of image sequences corresponding to the vessel of interest at different cardiac phases. These sequences are registered against the sequence of the end-diastolic phase to remove transversal and longitudinal rigid motions prescribed by the moving environment due to the heartbeat. Then, optical flow between the image sequences is computed to obtain the displacement fields of the vessel (each associated to a certain pressure level). The obtained displacement fields are regarded as observations within a data assimilation paradigm, which aims to estimate the material parameters of the tissues within the vessel wall. Specifically, a reduced order unscented Kalman filter is employed, endowed with a forward operator which amounts to address the solution of a hyperelastic solid mechanics model in the finite strain regime taking into account the axially stretched state of the vessel, as well as the effect of internal and external forces acting on the arterial wall. Due to the computational burden, a HPC approach is mandatory. Hence, the data assimilation and computational solid mechanics computations are parallelized at three levels: (i) a Kalman filter level; (ii) a cardiac phase level; and (iii) a mesh partitioning level. To illustrate the capabilities of this novel methodology toward the in-vivo analysis of patient-specific vessel constituents, mechanical material parameters are estimated using in-silico and in-vivo data retrieved from IVUS studies. Limitations and potentials of this approach are exposed and discussed.

Increases in Peripheral Systolic Pressure Levels and Z-score Associate Gradual Aortic Pressure Increase and Functional Arterial Impairment in Children and Adolescents.

BACKGROUND: Arterial changes associated with children and adolescents high blood pressure (HBP) states would vary depending on the arterial type, arterial indexes considered and/or on blood pressure (BP) levels. AIMS: To determine in children and adolescents: 1) if there is gradual structural-functional arterial impairment associated with gradual peripheral (brachial) systolic BP (pSBP) level or z-score increases, and 2) whether subjects with HBP levels and those with normal BP differ in the profiles of arterial changes associated with pSBP deviations. METHODS: 1005 asymptomatic children and adolescents were included. Clinical, anthropometric and arterial non-invasive evaluations were performed. Heart rate, brachial BP, aortic BP and wavederived parameters (i.e. augmentation index), carotid and femoral diameters, blood velocities and elastic modulus, carotid intima-media thickness and aortic pulse wave velocity, were obtained. Two groups were assembled: Reference (without cardiovascular risk factors (CVRFs); n=379) and HBP (n=175). Additionally, subjects were ascribed to groups according to their pSBP z-scores (z-score ≤ 0, 0< z-score < 1 or z-score ≥ 1). Age and sex-related mean and standard deviation equations were obtained for each variable (Reference group). Using those equations, data (entire population) were converted into z-scores. Groups were compared (absolute and z-scored variables) before and after adjusting for cofactors (ANOVA/ANCOVA). Linear regression analyses were done considering: pSBP and z-pSBP (independent) and absolute levels and z-scores for hemodynamic and arterial indexes (dependent variables). Differences in hemodynamic and arterial levels and z-scores variations (dependent) associated with variations in pSBP and z-pSBP (independent variable) were assessed. The slopes of the models for Reference and HBP groups were compared. CONCLUSION: HBP states associate hemodynamic and arterial changes not explained by exposure to other CVRFs, anthropometric or demographic factors. The higher the pSBP deviations from ageand sex-expected mean value in the Reference group, the higher the hemodynamic and arterial indexes deviation. The pSBP-related variations in hemodynamic and arterial indexes would not differ depending on whether HBP states are present or not.

Quantitative Vascular Evaluation: From Laboratory Experiments to Point-of-Care Patient (Experimental Approach).

This paper illustrates the evolution of our knowledge of arterial mechanics from our initial research works up to the present time. Several techniques focusing on this topic in terms of our experience are discussed. An interdisciplinary team composed by different institutions from Argentina, Uruguay, France and Spain was created to conduct research, to train human resources and to fulfill the inevitable social role of gaining access to technological innovation to improve public health.

Carotid Artery Wall Thickness in Obese and Nonobese Adults With Obstructive Sleep Apnea Before and Following Positive Airway Pressure Treatment.

Study objectives: Debate persists as to whether obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. The purpose of this study was to compare carotid intima-media thickness (IMT), an early sign of atherosclerosis, in obese and nonobese adults with OSA before and following positive airway pressure (PAP) treatment. Methods: A total of 206 adults newly diagnosed with OSA with an apnea-hypopnea index (AHI) of 15-75 events/hour and 53 controls with AHI <10 were studied. Waist circumference was used to classify participants as obese and nonobese. Bilateral common carotid artery B-mode ultrasound was performed at baseline to assess IMT, arterial diameter, arterial-wall mass, and circumferential wall stress. Measurements were repeated in 118 participants with OSA who completed a 4-month PAP treatment and had an average daily use over that period of ≥4 hours/day. Results: No significant differences in carotid IMT, diameter, or arterial-wall mass were present at baseline between participants with OSA and controls stratified by waist circumference, after adjusting for other cardiovascular risk factors. In participants with OSA, who had adequate PAP adherence over the 4-month treatment, carotid artery diameter significantly increased (mean change [95% confidence interval] = 0.13 [0.06, 0.20] mm; p = .0004), but no significant changes in carotid IMT, arterial-wall mass, and circumferential stress were observed in obese and nonobese participants. Conclusions: Regardless of obesity status, carotid IMT is not increased in adults with moderate to severe OSA versus controls and does not change following 4 months of PAP treatment.

Mechanical properties of normal and diseased cerebrovascular system.

BACKGROUND: Blood vessel mechanics has traditionally been of interest to researchers and clinicians. Changes in mechanical properties of arteries have been associated with various diseases. OBJECTIVE: To provide a comprehensive review directed towards understanding the basic biomechanical properties of cerebral arteries under normal and diseased conditions. METHODS: Literature review supplemented by personal knowledge. RESULTS: The mechanical properties of vascular tissue may depend on several factors including macromolecular volume fraction, molecular orientation, and volume or number of cells such as smooth muscle cells. Mechanical properties of a blood vessel have been characterized using different methods such as in vitro tensile testing, non-invasive ultrasound examination, and mathematical models. Experiments are complicated by the variation in properties and content of materials that make up the vessel wall and more challenging as the size of the vessel of interest decreases. Therapeutic interventions aiming to alter the mechanical response are either pharmaceutical: including calcium channel blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and ß-blockers; or, mechanical interventions such as angioplasty, stent placement, mechanical thrombectomy, or embolization procedures. CONCLUSION: It is apparent from the literature that macromolecular and cellular mechanics of blood vessels are not fully understood. Therefore, further studies are necessary to better understand contribution of these mechanisms to the overall mechanics of the vascular tissue.

MODELACIÓN POR ELEMENTOS FINITOS EN UN MODELO DE ANEURISMA

En un modelo con características geométricas y un comportamiento mecánico de la pared arterial generalizado para aneurismas periféricos, se realiza una modelación por elementos finitos (MEF) del efecto de la presión arterial y del espesor de la pared arterial en el saco de un aneurisma. Se analizan los esfuerzos de Von Misses, los esfuerzos tensores transversales y el desplazamiento en el saco del aneurisma. Se encuentra que el lugar más propenso a la ruptura para esta geometría de aneurismas es la región circundante a la arteria eferente y opuesta al flujo aferente. Se propone un proceso para realizar MEF en cualquier geometría de aneurisma y condiciones de presión, para analizar el riesgo y el lugar más probable de la ruptura.

Considering a model with generalized geometry and mechanical properties of the arterial wall for the peripheral vasculature aneurisms, a finite element modeling (FEM) is developed for analyzing the effects of arterial blood pressure and the arterial wall thickness in the aneurismal sac. The von Misses stresses, the transversal tensor stresses and the displacement in the aneurismal sac wall are analyzed. The possible site of rupture for this aneurism geometry is found surrounding the efferent artery and opposed to the flow inlet. A method for applying FEM to any aneurism geometry and blood pressure conditions is proposed for analyzing the risk of rupture and possible rupture site.