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Research Papers

J Biomech Eng. 2016;139(1):011001-011001-10. doi:10.1115/1.4034657.

An existing axisymmetric fluid/structure-interaction (FSI) model of the spinal cord, pia mater, subarachnoid space, and dura mater in the presence of syringomyelia and subarachnoid-space stenosis was modified to include porous solids. This allowed investigation of a hypothesis for syrinx fluid ingress from cerebrospinal fluid (CSF). Gross model deformation was unchanged by the addition of porosity, but pressure oscillated more in the syrinx and the subarachnoid space below the stenosis. The poroelastic model still exhibited elevated mean pressure in the subarachnoid space below the stenosis and in the syrinx. With realistic cord permeability, there was slight oscillatory shunt flow bypassing the stenosis via the porous tissue over the syrinx. Weak steady streaming flow occurred in a circuit involving craniocaudal flow through the stenosis and back via the syrinx. Mean syrinx volume was scarcely altered when the adjacent stenosis bisected the syrinx, but increased slightly when the syrinx was predominantly located caudal to the stenosis. The fluid content of the tissues over the syrinx oscillated, absorbing most of the radial flow seeping from the subarachnoid space so that it did not reach the syrinx. To a lesser extent, this cyclic swelling in a boundary layer of cord tissue just below the pia occurred all along the cord, representing a mechanism for exchange of interstitial fluid (ISF) and cerebrospinal fluid which could explain recent tracer findings without invoking perivascular conduits. The model demonstrates that syrinx volume increase is possible when there is subarachnoid-space stenosis and the cord and pia are permeable.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011002-011002-11. doi:10.1115/1.4034833.

Cardiovascular diseases are currently the leading cause of mortality in the population of developed countries, due to the constant increase in cardiovascular risk factors, such as high blood pressure, cholesterol, overweight, tobacco use, lack of physical activity, etc. Numerous prospective and retrospective studies have shown that arterial stiffening is a relevant predictor of these diseases. Unfortunately, the arterial stiffness distribution across the human body is difficult to measure experimentally. We propose a numerical approach to determine the arterial stiffness distribution of an arterial network using a subject-specific one-dimensional model. The proposed approach calibrates the optimal parameters of the reduced-order model, including the arterial stiffness, by solving an inverse problem associated with the noninvasive in vivo measurements. An uncertainty quantification analysis has also been carried out to measure the contribution of the model input parameters variability, alone or by interaction with other inputs, to the variation of clinically relevant hemodynamic indices, here the arterial pulse pressure. The results obtained for a lower limb model, demonstrate that the numerical approach presented here can provide a robust and subject-specific tool to the practitioner, allowing an early and reliable diagnosis of cardiovascular diseases based on a noninvasive clinical examination.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011003-011003-7. doi:10.1115/1.4034832.

This work deals with the viscoelasticity of the arterial wall and its influence on the pulse waves. We describe the viscoelasticity by a nonlinear Kelvin–Voigt model in which the coefficients are fitted using experimental time series of pressure and radius measured on a sheep's arterial network. We obtained a good agreement between the results of the nonlinear Kelvin–Voigt model and the experimental measurements. We found that the viscoelastic relaxation time—defined by the ratio between the viscoelastic coefficient and the Young's modulus—is nearly constant throughout the network. Therefore, as it is well known that smaller arteries are stiffer, the viscoelastic coefficient rises when approaching the peripheral sites to compensate the rise of the Young's modulus, resulting in a higher damping effect. We incorporated the fitted viscoelastic coefficients in a nonlinear 1D fluid model to compute the pulse waves in the network. The damping effect of viscoelasticity on the high-frequency waves is clear especially at the peripheral sites.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011004-011004-11. doi:10.1115/1.4034993.

A triaxial force-sensitive microrobot was developed to dynamically perturb skin in multiple deformation modes, in vivo. Wiener static nonlinear identification was used to extract the linear dynamics and static nonlinearity of the force–displacement behavior of skin. Stochastic input forces were applied to the volar forearm and thenar eminence of the hand, producing probe tip perturbations in indentation and tangential extension. Wiener static nonlinear approaches reproduced the resulting displacements with variances accounted for (VAF) ranging 94–97%, indicating a good fit to the data. These approaches provided VAF improvements of 0.1–3.4% over linear models. Thenar eminence stiffness measures were approximately twice those measured on the forearm. Damping was shown to be significantly higher on the palm, whereas the perturbed mass typically was lower. Coefficients of variation (CVs) for nonlinear parameters were assessed within and across individuals. Individual CVs ranged from 2% to 11% for indentation and from 2% to 19% for extension. Stochastic perturbations with incrementally increasing mean amplitudes were applied to the same test areas. Differences between full-scale and incremental reduced-scale perturbations were investigated. Different incremental preloading schemes were investigated. However, no significant difference in parameters was found between different incremental preloading schemes. Incremental schemes provided depth-dependent estimates of stiffness and damping, ranging from 300 N/m and 2 Ns/m, respectively, at the surface to 5 kN/m and 50 Ns/m at greater depths. The device and techniques used in this research have potential applications in areas, such as evaluating skincare products, assessing skin hydration, or analyzing wound healing.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011005-011005-7. doi:10.1115/1.4034429.

Arteriovenous fistulae (AVF) are the favored choice of vascular access but still have poor long-term success. Hemodynamic parameters play an important role in vascular health and have been linked to the development of intimal hyperplasia (IH), a pathological growth of the blood vessel initiated by injury. This study aimed to investigate the hemodynamics surrounding the arterial needle (AN) and venous needle (VN), using computational fluid dynamics. A range of blood flow rates, needle positions, and needle orientations were examined. Disturbed flows were found around AN tip in both antegrade and retrograde orientations, which result in regions of high residency time on the surface of the vein and may disrupt endothelial function. Conversely, a high speed jet exits the VN, which produced high wall shear stresses (WSSs) at the point of impingement which can damage the endothelium. The secondary flows produced by jet dissipation also resulted in regions of high residency time, which may influence endothelial structure, leading to IH. The use of shallow needle angles, a blood flow rate of approximately 300 ml/min, and placement of the needle tip away from the walls of the vein mitigates this risk.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011006-011006-9. doi:10.1115/1.4034710.

An abdominal aortic aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta of at least 1.5 times its normal diameter. Although the criterion of maximum diameter is still used in clinical practice to decide on a timely intervention, numerical studies have demonstrated the importance of other geometric factors. However, the major drawback of numerical studies is that they must be validated experimentally before clinical implementation. This work presents a new methodology to verify wall stress predicted from the numerical studies against the experimental testing. To this end, four AAA phantoms were manufactured using vacuum casting. The geometry of each phantom was subject to microcomputed tomography (μCT) scanning at zero and three other intraluminal pressures: 80, 100, and 120 mm Hg. A zero-pressure geometry algorithm was used to calculate the wall stress in the phantom, while the numerical wall stress was calculated with a finite-element analysis (FEA) solver based on the actual zero-pressure geometry subjected to 80, 100, and 120 mm Hg intraluminal pressure loading. Results demonstrate the moderate accuracy of this methodology with small relative differences in the average wall stress (1.14%). Additionally, the contribution of geometric factors to the wall stress distribution was statistically analyzed for the four phantoms. The results showed a significant correlation between wall thickness and mean curvature (MC) with wall stress.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011007-011007-9. doi:10.1115/1.4034651.

The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011008-011008-8. doi:10.1115/1.4034992.

In this work, contributing factors for red blood cell (RBC) damage in turbulence are investigated by simulating jet flow experiments. Results show that dissipative eddies comparable or smaller in size to the red blood cells cause hemolysis and that hemolysis corresponds to the number and, more importantly, the surface area of eddies that are associated with Kolmogorov length scale (KLS) smaller than about 10 μm. The size distribution of Kolmogorov scale eddies is used to define a turbulent flow extensive property with eddies serving as a means to assess the turbulence effectiveness in damaging cells, and a new hemolysis model is proposed. This empirical model is in agreement with hemolysis results for well-defined systems that exhibit different exposure times and flow conditions, in Couette flow viscometer, capillary tube, and jet flow experiments.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011009-011009-9. doi:10.1115/1.4034995.

This study is a collaborative effort among lactation specialists and fluid dynamic engineers. The paper presents clinical results for suckling pressure pattern in lactating human breast as well as a 3D computational fluid dynamics (CFD) modeling of milk flow using these clinical inputs. The investigation starts with a careful, statistically representative measurement of suckling vacuum pressure, milk flow rate, and milk intake in a group of infants. The results from clinical data show that suckling action does not occur with constant suckling rate but changes in a rhythmic manner for infants. These pressure profiles are then used as the boundary condition for the CFD study using commercial ansys fluent software. For the geometric model of the ductal system of the human breast, this work takes advantage of a recent advance in the development of a validated phantom that has been produced as a ground truth for the imaging applications for the breast. The geometric model is introduced into CFD simulations with the aforementioned boundary conditions. The results for milk intake from the CFD simulation and clinical data were compared and cross validated. Also, the variation of milk intake versus suckling pressure are presented and analyzed. Both the clinical and CFD simulation show that the maximum milk flow rate is not related to the largest vacuum pressure or longest feeding duration indicating other factors influence the milk intake by infants.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011010-011010-7. doi:10.1115/1.4035262.

Ex vivo mechanical testing has provided tremendous insight toward prediction of the in vivo mechanical behavior and local mechanical environment of the arterial wall; however, the role of perivascular support on the local mechanical behavior of arteries is not well understood. Here, we present a novel approach for quantifying the impact of the perivascular support on arterial mechanics using intravascular ultrasound (IVUS) on cadaveric porcine hearts. We performed pressure-diameter tests (n = 5) on the left anterior descending coronary arteries (LADCAs) in situ while embedded in their native perivascular environment using IVUS imaging and after removal of the perivascular support of the artery. We then performed standard cylindrical biaxial testing on these vessels ex vivo and compared the results. Removal of the perivascular support resulted in an upward shift of the pressure-diameter curve. Ex vivo testing, however, showed significantly lower circumferential compliance compared to the in situ configuration. On a second set of arteries, local axial stretch ratios were quantified (n = 5) along the length of the arteries. The average in situ axial stretch ratio was 1.28 ± 0.16; however, local axial stretch ratios showed significant variability, ranging from 1.01 to 1.70. Taken together, the data suggest that both the perivascular loading and the axial tethering have an important role in arterial mechanics. Combining nondestructive testing using IVUS with traditional ex vivo cylindrical biaxial testing yields a more comprehensive assessment of the mechanical behavior of arteries.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011011-011011-11. doi:10.1115/1.4035122.

The purpose of this work is to predict the effect of impaired red blood cells (RBCs) deformability on blood flow conditions in human carotid artery bifurcation. First, a blood viscosity model is developed that predicts the steady-state blood viscosity as a function of shear rate, plasma viscosity, and mechanical (and geometrical) properties of RBC's. Viscosity model is developed by modifying the well-known Krieger and Dougherty equation for monodisperse suspensions by using the dimensional analysis approach. With the approach, we manage to account for the microscopic properties of RBC's, such as their deformability, in the macroscopic behavior of blood via blood viscosity. In the second part of the paper, the deduced viscosity model is used to numerically predict blood flow conditions in human carotid artery bifurcation. Simulations are performed for different values of RBC's deformability and analyzed by investigating parameters, such as the temporal mean wall shear stress (WSS), oscillatory shear index (OSI), and mean temporal gradient of WSS. The analyses show that the decrease of RBC's deformability decrease the regions of low WSS (i.e., sites known to be prevalent at atherosclerosis-prone regions); increase, in average, the value of WSS along the artery; and decrease the areas of high OSI. These observations provide an insight into the influence of blood's microscopic properties, such as the deformability of RBC's, on hemodynamics in larger arteries and their influence on parameters that are known to play a role in the initiation and progression of atherosclerosis.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):011012-011012-7. doi:10.1115/1.4035265.

The goal of this study was to characterize antibody penetration through cartilage tissue under mechanical loading. Mechanical stimulation aids in the penetration of some proteins, but this effect has not characterized molecules such as antibodies (>100 kDa), which may hold some clinical value for treating osteoarthritis (OA). For each experiment, fresh articular cartilage plugs were obtained and exposed to fluorescently labeled antibodies while under cyclic mechanical load in unconfined compression for several hours. Penetration of these antibodies was quantified using confocal microscopy, and finite element (FE) simulations were conducted to predict fluid flow patterns within loaded samples. Transport enhancement followed a linear trend with strain amplitude (0.25–5%) and a nonlinear trend with frequency (0.25–2.60 Hz), with maximum enhancement found to be at 5% cyclic strain and 1 Hz, respectively. Regions of highest enhancement of transport within the tissue were associated with the regions of highest interstitial fluid velocity, as predicted from finite-element simulations. Overall, cyclic compression-enhanced antibody transport by twofold to threefold. To our knowledge, this is the first study to test how mechanical stimulation affects the diffusion of antibodies in cartilage and suggest further study into other important factors regarding macromolecular transport.

Commentary by Dr. Valentin Fuster

Technical Brief

J Biomech Eng. 2016;139(1):014501-014501-11. doi:10.1115/1.4034867.

Accurate stress and strain calculations are important for plaque progression and vulnerability assessment. Models based on in vivo data often need to form geometries with zero-stress/strain conditions. The goal of this paper is to use IVUS-based near-idealized geometries and introduce a three-step model construction process to include residual stress, axial shrinkage, and circumferential shrinkage and investigate their impacts on stress and strain calculations. In Vivo intravascular ultrasound (IVUS) data of human coronary were acquired for model construction. In Vivo IVUS movie data were acquired and used to determine patient-specific material parameter values. A three-step modeling procedure was used to make our model: (a) wrap the zero-stress vessel sector to obtain the residual stress; (b) stretch the vessel axially to its length in vivo; and (c) pressurize the vessel to recover its in vivo geometry. Eight models were constructed for our investigation. Wrapping led to reduced lumen and cap stress and increased out boundary stress. The model with axial stretch, circumferential shrink, but no wrapping overestimated lumen and cap stress by 182% and 448%, respectively. The model with wrapping, circumferential shrink, but no axial stretch predicted average lumen stress and cap stress as 0.76 kPa and −15 kPa. The same model with 10% axial stretch had 42.53 kPa lumen stress and 29.0 kPa cap stress, respectively. Skipping circumferential shrinkage leads to overexpansion of the vessel and incorrect stress/strain calculations. Vessel stiffness increase (100%) leads to 75% lumen stress increase and 102% cap stress increase.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2016;139(1):014502-014502-6. doi:10.1115/1.4035263.

The feasibility of implementing magnetic struts into drug-eluting stents (DESs) to mitigate the adverse hemodynamics which precipitate stent thrombosis is examined. These adverse hemodynamics include platelet-activating high wall shear stresses (WSS) and endothelial dysfunction-inducing low wall shear stresses. By magnetizing the stent struts, two forces are induced on the surrounding blood: (1) magnetization forces which reorient red blood cells to align with the magnetic field and (2) Lorentz forces which oppose the motion of the conducting fluid. The aim of this study was to investigate whether these forces can be used to locally alter blood flow in a manner that alleviates the thrombogenicity of stented vessels. Two-dimensional steady-state computational fluid dynamics (CFD) simulations were used to numerically model blood flow over a single magnetic drug-eluting stent strut with a square cross section. The effects of magnet orientation and magnetic flux density on the hemodynamics of the stented vessel were elucidated in vessels transporting oxygenated and deoxygenated blood. The simulations are compared in terms of the size of separated flow regions. The results indicate that unrealistically strong magnets would be required to achieve even modest hemodynamic improvements and that the magnetic strut concept is ill-suited to mitigate stent thrombosis.

Commentary by Dr. Valentin Fuster

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