Arterial Wall Mechanics Research Articles

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.

Axial Wall Displacement at the Common Carotid Artery is Associated With the Lamb Waves

Abstract As compared with its radial wall displacement, axial wall displacement at the common carotid artery (CCA) carries independent clinical values, but its physical mechanisms are unclear. This study aims to investigate whether axial wall displacement at the CCA is solely from Young waves. A pulse wave propagation theory is utilized to identify two types of waves, Young waves, and Lamb waves, in an artery, and identifies two sources for axial wall displacement, wall shear stress and radial wall displacement gradient with a factor of the difference between axial and circumferential initial tension, which reveals the influence of axial initial tension on the waveform of axial wall displacement. Theoretical expressions are derived for calculating the waveforms of axial wall displacement and its two sources in the Young waves. With the measured pulsatile pressure and blood velocity at the CA of three healthy adults as the inputs, the waveforms of axial wall displacement in the Young waves are calculated at different values of axial initial tension and are found to greatly differ from their measured counterparts. As such, the Lamb waves may contribute to axial wall displacement at the CCA and the associated physical and physiological implications are discussed. Given the clinical values of axial wall displacement at the CCA, the Lamb waves may play a non-negligible role in determining arterial health and needs to be further studied for a comprehensive assessment of arterial wall mechanics.

The effect of aging on carotid artery wall mechanics during maximal resistance exercise.

Age-related stiffening of the large elastic arteries (e.g., common carotid artery [CCA]) may impair wall dynamics (i.e., strain) and amplify transmission of pulsatile blood flow into the brain with large increases in pressure that occur during maximal resistance exercise (RE). The purpose of this study was to compare CCA arterial wall dynamics, central hemodynamics, and cerebral blood velocity responses during maximal RE between young and older adults. Thirty-one young (YA; 26 ± 5 yrs; 23.8 ± 3.3kg/m2) and 25 older adults (OA; 60 ± 6 yrs; 30.0 ± 5.5kg/m2) performed a unilateral maximal isokinetic knee flexion/extension exercise protocol (i.e., maximal RE). All measures were recorded at baseline and during the last 10s of maximal RE. Common carotid artery strain, CCA strain time to peak, and CCA strain rate (i.e., variables of arterial wall dynamics) were analyzed using 2D speckle tracking software from circumferential ultrasound images. Transcranial Doppler was used to measure right middle cerebral artery (MCA) blood velocity. Non-invasive arterial blood pressure measurements were obtained using finger photoplethysmography. Older adults had greater reductions in CCA strain time to peak from baseline to maximal RE (345 ± 39 to 242 ± 52ms) than YA (308 ± 35 to 247 ± 42ms; interaction effect, p < 0.01). MCA velocity was similar between YA and OA during maximal RE (p = 0.48), despite a greater arterial pressor response in OA (p < 0.01). These data suggest cerebral blood velocity responds similarly during maximal RE among OA compared to YA, despite subtle age-related differences in the pressor and extracranial vascular response during maximal RE.

Assessing pulsatile waveforms of paravascular cerebrospinal fluid dynamics within the glymphatic pathways using dynamic diffusion-weighted imaging (dDWI)

Cerebrospinal fluid (CSF) in the paravascular spaces of the surface arteries (sPVS) is a vital pathway in brain waste clearance. Arterial pulsations may be the driving force of the paravascular flow, but its pulsatile pattern remains poorly characterized, and no clinically practical method for measuring its dynamics in the human brain is available. In this work, we introduce an imaging and quantification framework for in-vivo non-invasive assessment of pulsatile fluid dynamics in the sPVS. It used dynamic Diffusion-Weighted Imaging (dDWI) at a lower b-values of 150s/mm2 and retrospective gating to detect the slow flow of CSF while suppressing the fast flow of adjacent arterial blood. The waveform of CSF flow over a cardiac cycle was revealed by synchronizing the measurements with the heartbeat. A data-driven approach was developed to identify sPVS and allow automatic quantification of the whole-brain fluid waveforms. We applied dDWI to twenty-five participants aged 18-82 y/o. Results demonstrated that the fluid waveforms across the brain showed an explicit cardiac-cycle dependency, in good agreement with the vascular pumping hypothesis. Furthermore, the shape of the CSF waveforms closely resembled the pressure waveforms of the artery wall, suggesting that CSF dynamics is tightly related to artery wall mechanics. Finally, the CSF waveforms in aging participants revealed a strong age effect, with a significantly wider systolic peak observed in the older relative to younger participants. The peak widening may be associated with compromised vascular compliance and vessel wall stiffening in the older brain. Overall, the results demonstrate the feasibility, reproducibility, and sensitivity of dDWI for detecting sPVS fluid dynamics of the human brain. Our preliminary data suggest age-related alterations of the paravascular pumping. With an acquisition time of under six minutes, dDWI can be readily applied to study fluid dynamics in normal physiological conditions and cerebrovascular/neurodegenerative diseases.

Adaptation of Arterial Wall Viscosity to the Short‐Term Reduction of Heart Rate: Impact of Aging

BackgroundChanges in arterial wall viscosity, which dissipates the energy stored within the arterial wall, may contribute to the beneficial effect of heart rate (HR) reduction on arterial stiffness and cardiovascular coupling. However, it has never been assessed in humans and could be altered by aging. We evaluated the effect of a selective HR‐lowering agent on carotid arterial wall viscosity and the impact of aging on this effect.Methods and ResultsThis randomized, placebo‐controlled, double‐blind, crossover study performed in 19 healthy volunteers evaluated the effects of ivabradine (5 mg BID, 1‐week) on carotid arterial wall viscosity, mechanics, hemodynamics, and cardiovascular coupling. Arterial wall viscosity was evaluated by the area of the hysteresis loop of the pressure‐lumen cross‐sectional area relationship, representing the energy dissipated (WV), and by the relative viscosity (WV/WE), with WE representing the elastic energy stored.HR reduction by ivabradine increased WV and WE whereas WV/WE remained stable. In middle‐aged subjects (n=11), baseline arterial stiffness and cardiovascular coupling were less favorable, and WE was similar but WV and therefore WV/WE were lower than in youth (n=8). HR reduction increased WV/WE in middle‐aged but not in young subjects, owing to a larger increase in WV than WE. These results were supported by the age‐related linear increase in WV/WE after HR reduction (P=0.009), explained by a linear increase in WV.ConclusionHR reduction increases arterial wall energy dissipation proportionally to the increase in WE, suggesting an adaptive process to bradycardia. This mechanism is altered during aging resulting in a larger than expected energy dissipation, the impact of which should be assessed.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: 2015/077/HP. URL: https://www. eudract.ema.europa.eu; Unique identifier: 2015‐002060‐17.

Fluid-structure interaction simulation of tissue degradation and its effects on intra-aneurysm hemodynamics

Tissue degradation plays a crucial role in vascular diseases such as atherosclerosis and aneurysms. Computational modeling of vascular hemodynamics incorporating both arterial wall mechanics and tissue degradation has been a challenging task. In this study, we propose a novel finite element method-based approach to model the microscopic degradation of arterial walls and its interaction with blood flow. The model is applied to study the combined effects of pulsatile flow and tissue degradation on the deformation and intra-aneurysm hemodynamics. Our computational analysis reveals that tissue degradation leads to a weakening of the aneurysmal wall, which manifests itself in a larger deformation and a smaller von Mises stress. Moreover, simulation results for different heart rates, blood pressures and aneurysm geometries indicate consistently that, upon tissue degradation, wall shear stress increases near the flow-impingement region and decreases away from it. These findings are discussed in the context of recent reports regarding the role of both high and low wall shear stress for the progression and rupture of aneurysms.

Hemodynamic simulation of abdominal aortic aneurysm on idealised models: Investigation of stress parameters during disease progression

Background and ObjectiveAnalysis and prediction of rupture risk of abdominal aortic aneurysms (AAA) facilitates planning for surgical interventions and assessment of plausible treatment modalities. Present approach of using maximum diameter criterion, is giving way to hemodynamic and bio-mechanical based predictors in conjunction with Computational fluid dynamic (CFD) simulations. Detailed studies on hemodynamic and bio-mechanical parameters at the stage of maximum growth/rupture is of practical importance to the clinical community. However, understanding the changes in these parameters at different stages of growth, will be useful for clinicians, in planning routine monitoring to reduce the risk of sudden rupture. This is particularly useful in medical resource starved nations. Present study investigates the hemodynamic and bio-mechanical changes occurring during the growth stages of aortic aneurysms using fluid structure interaction (FSI) studies. MethodSix idealized fusiform aneurysm models spanning high (shorter) and low (longer) values of the shape index (DHr), have been analysed at three different stages of growth viz, a Dmax of 3.5cm, 4.25cm, 5cm. Pulsatile Newtonian blood flow, passing through an elastic arterial vessel wall with uniform thickness is assumed. Two-way coupled fluid structure interaction have been employed for the numerical simulation of blood flow dynamics and arterial wall mechanics. ResultsWall shear stress (WSS) parameters and vonmises stress indicators, co-relating rupture and thrombus formation, have been extracted and reported, at each growth stage. When the aneurysm progresses in diameter, the areas recording abnormally low TAWSS, as well as areas of high/low OSI were found to increase at different rates for shorter and longer aneurysms. Moreover, drastic increase in the maximum wall stresses (MWS) and wall displacement were observed as the aneurysm approached the critical diameter. ConclusionHemodynamic predictors were found to be highly dependent on the shape index (DHr), when the aneurysm was small, whereas significant influence of DHr on the wall stresses happens, as the aneurysm approaches the critical diameter. Inconsistent variation of these indicators exhibited by shorter aneurysms (high DHr) at different growth stages, demands routine monitoring (using scans), of such aneurysms, to prevent unexpected rupture.

A comparison of passive and active wall mechanics between elastic and muscular arteries of juvenile and adult rats

The elastic abdominal aorta and muscular femoral artery are susceptible to aneurysm and atherosclerosis, respectively. The vessel wall mechanics should be an important element for the difference. The objective of the study is to demonstrate a comparison of vessel wall mechanics between elastic and muscular arteries of juvenile and adult rats to show the changes of mechanical properties relevant to aging. The passive and active mechanical tests, theoretical analysis, and histological evaluation were carried out to investigate mechanical properties of vessel walls in the abdominal aorta and carotid and femoral arteries of young and adult rats. There are stiffening femoral artery, unchanged carotid artery, and distensible abdominal aorta in adult rats as compared with the young. The opening angle has values of 54 ± 13°, 82 ± 13°, and 94 ± 13° in the abdominal aorta and carotid and femoral arteries of adult rats, respectively, as well as 80 ± 22°, 93 ± 19°, and 100 ± 23° in the young. The findings are explained by the significantly reduced width of collagen fibers in the abdominal aorta, relatively unchanged width in the carotid artery, and significantly increased width in the femoral artery of adult rats as compared with the young. In conjunction with available literatures, we concluded that inconsistency for nonlinear age-related changes of artery wall mechanics occurs between arteries of different types, which may be a risk factor for the occurrence of abdominal aorta aneurysm and femoral artery atherosclerosis.

Five years of cardio-ankle vascular index (CAVI) and CAVI0: how close are we to a pressure-independent index of arterial stiffness?

Pulse wave velocity, a common metric of arterial stiffness, is an established predictor for cardiovascular events and mortality. However, its intrinsic pressure-dependency complicates the discrimination of acute and chronic impacts of increased blood pressure on arterial stiffness. Cardio-ankle vascular index (CAVI) represented a significant step towards the development of a pressure-independent arterial stiffness metric. However, some potential limitations of CAVI might render this arterial stiffness metric less pressure-independent than originally thought. For this reason, we later introduced CAVI0. Nevertheless, advantages of one approach over the other are left debated. This review aims to shed light on the pressure (in)dependency of both CAVI and CAVI0. By critically reviewing results from studies reporting both CAVI and CAVI0 and using simple analytical methods, we show that CAVI0 may enhance the pressure-independent assessment of arterial stiffness, especially in the presence of large inter-individual differences in blood pressure.

Prenatal hypoxia affects scaling of blood pressure and arterial wall mechanics in the common snapping turtle, Chelydra serpentina

In reptiles, exposure to hypoxia during embryonic development affects several cardiovascular parameters. These modifications may impose different mechanical stress to the arterial system, and we speculated that the arterial wall of major outflow vessels would be modified accordingly. Since non-crocodilian reptiles possess a partially divided ventricle, ensuing similar systemic and pulmonary systolic pressures, we investigated how morphological and mechanical properties of segments from the left aortic arch (LAo) and the proximal and distal segments of the left pulmonary artery (LPAp and LPAd, respectively) change as body mass (Mb) increases. Eggs from common snapping turtles, Chelydra serpentina, were incubated under normoxia (21% O2; N21) or hypoxia (10% O2; H10), hatched and maintained in normoxia thereafter. Turtles (0.11–6.85 kg) were cannulated to measure arterial pressures, and an injection of adrenaline was used to increase pressures. Portions of the LAo, LPAp and LPAd were fixed under physiological hydrostatic pressures for histology and mechanical assessment. Arterial pressures increased with Mb for N21 but not for H10. Although mechanical and functional characteristics from the LPAp and LPAd were similar between N21 and H10, wall thickness from LAo did not change with Mb in the H10 group, thus wall stress increased in larger turtles. This indicates that larger H10 turtles probably experience an elevated probability of arterial wall rupture without concomitant changes in the cardiovascular system to prevent it. Finally, collagen content of the LPAp and LAo was smaller than in LPAd, suggesting a more distensible arterial wall could attenuate higher pressures from larger turtles.

Review of the Techniques Used for Investigating the Role Elastin and Collagen Play in Arterial Wall Mechanics.

The arterial wall is characterised by a complex microstructure that impacts the mechanical properties of the vascular tissue. The main components consist of collagen and elastin fibres, proteoglycans, Vascular Smooth Muscle Cells (VSMCs) and ground matrix. While VSMCs play a key role in the active mechanical response of arteries, collagen and elastin determine the passive mechanics. Several experimental methods have been designed to investigate the role of these structural proteins in determining the passive mechanics of the arterial wall. Microscopy imaging of load-free or fixed samples provides useful information on the structure-function coupling of the vascular tissue, and mechanical testing provides information on the mechanical role of collagen and elastin networks. However, when these techniques are used separately, they fail to provide a full picture of the arterial micromechanics. More recently, advances in imaging techniques have allowed combining both methods, thus dynamically imaging the sample while loaded in a pseudo-physiological way, and overcoming the limitation of using either of the two methods separately. The present review aims at describing the techniques currently available to researchers for the investigation of the arterial wall micromechanics. This review also aims to elucidate the current understanding of arterial mechanics and identify some research gaps.

Experimental measurement and modeling analysis of active and passive mechanical properties of arterial vessel wall

Coronary artery diseases (CAD) have always been serious threats to human health. The measurement, constitutive modeling, and analysis of mechanical properties of the blood vessel wall can provide a tool for disease diagnosis, stent implantation, and artificial artery design. The vessel wall has both active and passive mechanical properties. The passive mechanical properties are mainly determined by elastic and collagen fibers, and the active mechanical properties are determined by the contraction of vascular smooth muscle cells (VSMC). Substantial studies have shown that, the two-layer model of the vessel wall can feature the mechanical properties well, and the circumferential, axial and radial strain and stress are of great significance in arterial wall mechanics. This study reviewed recent investigations of mechanical properties of the vessel wall. Challenges and opportunities in this area are discussed relevant to the clinical treatment of coronary artery diseases.

Iliac Veins Are More Compressible Than Iliac Arteries: A New Method of Testing.

Incompressibility implies that a tissue preserves its volume regardless of the loading conditions. Although this assumption is well-established in arterial wall mechanics, it is assumed to apply for the venous wall without validation. The objective of this study is to test whether the incompressibility assumption holds for the venous wall. To investigate the vascular wall volume under different loading conditions, inflation-extension testing protocol was used in conjunction with intravascular ultrasound (IVUS) in both common iliac arteries (n = 6 swine) and common iliac veins (n = 9 dogs). Use of IVUS allows direct visualizations of lumen dimensions simultaneous with direct measurements of outer dimensions during loading. The arterial tissue was confirmed to preserve volume during various load conditions (p = 0.11) consistent with the literature, while the venous tissue was found to lose volume (about 35%) under loaded conditions (p < 0.05). Using a novel methodology, this study shows the incompressibility assumption does not hold for the venous wall especially at higher pressures, which suggests that there may be fluid loss through the vein wall during loading. This has important implications for coupling of fluid transport across the wall and biomechanics of the wall in healthy and diseased conditions.

An extended exponentiated Hencky energy for transverse isotropy

AbstractIn this contribution we aim to formally extend the promising exponentiated Hencky strain‐energy to transversely isotropic problems. This is facilitated by using additional anisotropic logarithmic strain invariants. The potential of the logarithmic‐strain driven material response is studied for a numerical example associated to arterial wall mechanics in order to draw a comparison to a more classical material formulation based on the right Cauchy‐Green tensor.

Carotid artery wall mechanics in young males with high cardiorespiratory fitness.

What is the central question of this study? Common carotid artery (CCA) two-dimensional strain imaging detects intrinsic arterial wall properties beyond conventional measures of arterial stiffness, but the effect of cardiorespiratory fitness on two-dimensional strain-derived indices of CCA stiffness is unknown. What is the main finding and its importance? Two-dimensional strain imaging of the CCA revealed greater peak circumferential strain and systolic strain rate in highly fit men compared with their less fit counterparts. Altered CCA wall mechanics might reflect intrinsic training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise. The influence of cardiorespiratory fitness on arterial stiffness in young adults remains equivocal. Beyond conventional measures of arterial stiffness, two-dimensional strain imaging of the common carotid artery (CCA) provides new information related to the intrinsic properties of the arterial wall. Therefore, the aim of this study was to assess the effect of cardiorespiratory fitness on both conventional indices of CCA stiffness and two-dimensional strain parameters, at rest and after a bout of aerobic exercise in young, healthy men. Short-axis ultrasound images of the CCA were recorded in 34 healthy men {22years old [95% confidence interval (CI), 19, 22]} before and immediately after 5min of aerobic exercise (40% of maximal oxygen consumption). Images were analysed for arterial diameter, peak circumferential strain (PCS) and peak systolic and diastolic strain rates (S-SR and D-SR). Heart rate, systolic and diastolic blood pressure were simultaneously assessed, and Peterson's elastic modulus (Ep ) and β-stiffness (β1 ) were calculated. Participants were separated post hoc into moderate- and high-fitness groups [maximal oxygen consumption, 48.9 (95% CI, 44.7, 53.2) versus 65.6mlkg-1 min-1 (95% CI, 63.1, 68.1), respectively; P<0.001]. The Ep and β1 were similar between groups at baseline (P>0.13) but were elevated in the moderate-fitness group postexercise (P<0.04). The PCS and S-SR were elevated in the high-fitness group at both time points [3.0% (95% CI,1.2, 4.9), P=0.002, and 0.401s-1 (95% CI,0.085, 0.72), P=0.02, respectively]. No group differences were observed in CCA heart rate, systolic or diastolic blood pressure or D-SR throughout the protocol (P>0.05). Highly fit individuals exhibit elevated CCA, PCS and S-SR, which might reflect training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise.

Effect of distal thickening and stiffening of plaque cap on arterial wall mechanics.

To investigate the effect of longitudinal variations of cap thickness and tissue properties on wall stresses and strains along the atherosclerotic stenosis, stenotic plaque models (uniformly thick, distally thickened, homogenous, and distally stiffened) were constructed and subjected to computational stress analyses with due consideration of fluid-structure interactions (FSI). The analysis considered three different cap thicknesses-45, 65, and 200μm-and tissue properties-soft, fibrous, and hard. The maximum peak cap stress (PCS) and strain were observed in the upstream throat section and demonstrated increases of the order of 345 and 190%, respectively, as the cap thickness was reduced from 200 to 45μm in uniformly thick models. Distal stiffening increased PCS in the downstream region; however, the overall effect of this increase was rather small. Distal thickening did not affect maximum PCS and strain values for cap thicknesses exceeding 65μm; however, a noticeable increase in maximum PCS and corresponding longitudinal variation (or spatial gradient) in stress was observed in the very thin (45-μm-thick) cap. It was, therefore, inferred that existence of a rather thin upstream cap demonstrating distal cap thickening indicates an increased risk of plaque progression and rupture. Graphical Abstract ᅟ.

Assessing Collagen and Elastin Pressure-dependent Microarchitectures in Live, Human Resistance Arteries by Label-free Fluorescence Microscopy.

The pathogenic contribution of resistance artery remodeling is documented in essential hypertension, diabetes and the metabolic syndrome. Investigations and development of microstructurally motivated mathematical models for understanding the mechanical properties of human resistance arteries in health and disease have the potential to aid understanding how disease and medical treatments affect the human microcirculation. To develop these mathematical models, it is essential to decipher the relationship between the mechanical and microarchitectural properties of the microvascular wall. In this work, we describe an ex vivo method for passive mechanical testing and simultaneous label-free three-dimensional imaging of the microarchitecture of elastin and collagen in the arterial wall of isolated human resistance arteries. The imaging protocol can be applied to resistance arteries of any species of interest. Image analyses are described for quantifying i) pressure-induced changes in internal elastic lamina branching angles and adventitial collagen straightness using Fiji and ii) collagen and elastin volume densities determined using Ilastik software. Preferably all mechanical and imaging measurements are performed on live, perfused arteries, however, an alternative approach using standard video-microscopy pressure myography in combination with post-fixation imaging of re-pressurized vessels is discussed. This alternative method provides users with different options for analysis approaches. The inclusion of the mechanical and imaging data in mathematical models of the arterial wall mechanics is discussed, and future development and additions to the protocol are proposed.

Stiff vessels approached in a flexible way: Advancing quantification and interpretation of arterial stiffness

IntroductionAlthough pulse wave velocity (PWV), a proxy of arterial stiffness, is a strong predictor of cardiovascular complications, it is confounded by blood pressure (BP) and heart rate at the time of examination. Furthermore, establishing whether an artery behaves stiffer or less stiff does not inform a clinician on the cause of the stiffening. Quantification of arterial stiffnessThis paper focuses on BP as a confounder of PWV. We developed a method to patient-specifically determine the dependence of PWV on BP — on average 1 m/s per 10 mmHg diastolic BP — and used it to disentangle BP-dependent and -independent stiffening in hypertension and cancer patients. We furthermore showed that the so-called cardio-ankle vascular index (CAVI) — a measure deemed BP-independent — shows a residual BP-dependence that is readily correctable using a modified equation (CAVI0). Both developed methods are directly applicable to clinical measurements in individual patients. Interpretation of arterial stiffnessWe developed a computer modelling procedure to disentangle contributions of the individual wall components — collagen, elastin, and smooth muscle — to arterial stiffening as observed in patients. Our model-based approach shows that with ageing, the biomechanical phenotype shifts from elastin-dominated to collagen-dominated load bearing.Model-based assessment of arterial wall mechanics provides a promising tool to further improve interpretation of arterial stiffness measurements in patients. Further development of such methodology applied to various mouse models may improve the understanding and interpretation of arterial stiffening in ageing and disease.

Uncertainty quantification and sensitivity analysis of an arterial wall mechanics model for evaluation of vascular drug therapies

Quantification of the uncertainty in constitutive model predictions describing arterial wall mechanics is vital towards non-invasive assessment of vascular drug therapies. Therefore, we perform uncertainty quantification to determine uncertainty in mechanical characteristics describing the vessel wall response upon loading. Furthermore, a global variance-based sensitivity analysis is performed to pinpoint measurements that are most rewarding to be measured more precisely. We used previously published carotid diameter–pressure and intima–media thickness (IMT) data (measured in triplicate), and Holzapfel–Gasser–Ogden models. A virtual data set containing 5000 diastolic and systolic diameter–pressure points, and IMT values was generated by adding measurement error to the average of the measured data. The model was fitted to single-exponential curves calculated from the data, obtaining distributions of constitutive parameters and constituent load bearing parameters. Additionally, we (1) simulated vascular drug treatment to assess the relevance of model uncertainty and (2) evaluated how increasing the number of measurement repetitions influences model uncertainty. We found substantial uncertainty in constitutive parameters. Simulating vascular drug treatment predicted a 6% point reduction in collagen load bearing (L_mathrm {coll}), approximately 50% of its uncertainty. Sensitivity analysis indicated that the uncertainty in L_{mathrm {coll}} was primarily caused by noise in distension and IMT measurements. Spread in L_{mathrm {coll}} could be decreased by 50% when increasing the number of measurement repetitions from 3 to 10. Model uncertainty, notably that in L_{mathrm {coll}}, could conceal effects of vascular drug therapy. However, this uncertainty could be reduced by increasing the number of measurement repetitions of distension and wall thickness measurements used for model parameterisation.

Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries.

The impact of disease-related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared with frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure-induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as a model system, integrating vital imaging, pressure myography, and mathematical modeling. Collagenase and elastase digestions were applied to evaluate the load-bearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both R2 ≥ 0.99), whereas there was a nonlinear relationship to the internal elastic lamina elastin fiber branching angles. Mathematical modeling suggested a collagen recruitment strain (means ± SE) of 1.1 ± 0.2 circumferentially and 0.20 ± 0.01 longitudinally, corresponding to a pressure of ~40 mmHg, a finding supported by the vital imaging. The integrated method was tested on human PRA to confirm its validity. These showed limited circumferential distensibility and elongation and a collagen recruitment strain of 0.8 ± 0.1 circumferentially and 0.06 ± 0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was confirmed by vital imaging showing negligible microarchitectural changes of elastin and collagen upon pressurization. In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies.NEW & NOTEWORTHY This is the first study to quantitatively relate pressure-induced microstructural changes in resistance arteries to the mechanics of their wall. Principal findings using a pig model system were confirmed in human arteries. The combined methods provide a strong tool for future hypothesis-driven studies of microvascular pathologies.