Research Papers

J Biomech Eng. 2018;140(4):041001-041001-7. doi:10.1115/1.4038358.

When optical motion capture is used for motion analysis, reflective markers or a digitizer are typically used to record the location of anatomical landmarks identified through palpation. The landmarks are then used to construct anatomical coordinate systems. Failure to consistently identify landmarks through palpation over repeat tests creates artifacts in the kinematic waveforms. The purpose of this work was to improve intra- and inter-rater reliability in determining lower limb anatomical landmarks and the associated anatomical coordinate systems using a marker alignment device (MAD). The device aids the subject in recreating the same standing posture over multiple tests, and recreates the anatomical landmarks from previous static calibration trials. We tested three different raters who identified landmarks on eleven subjects. The subjects performed walking trials and their gait kinematics were analyzed with and without the device. Ankle kinematics were not improved by the device suggesting manual palpation over repeat visits is just as effective as the MAD. Intra-class correlation coefficients between gait kinematics registered to the reference static trial and registered to follow-up static trials with and without the device were improved between 1% and 33% when the device was used. Importantly, out-of-plane hip and knee kinematics showed the greatest improvements in repeatability. These results suggest that the device is well suited to reducing palpation artifact during repeat visits to the gait lab.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041002-041002-10. doi:10.1115/1.4038202.

Nanoparticle (NP)-based drug delivery is a promising method to increase the therapeutic index of anticancer agents with low median toxic dose. The delivery efficiency, corresponding to the fraction of the injected NPs that adhere to the tumor site, depends on NP size a and aspect ratio AR. Values for these variables are currently chosen empirically, which may not result in optimal targeted drug delivery. This study applies rigorous optimization to the design of NPs. A preliminary investigation revealed that delivery efficiency increases monotonically with a and AR. However, maximizing a and AR results in nonuniform drug distribution, which impairs tumor regression. Therefore, a multiobjective optimization (MO) problem is formulated to quantify the trade-off between NPs accumulation and distribution. The MO is solved using the derivative-free mesh adaptive direct search algorithm. Theoretically, the Pareto-optimal set consists of an infinite number of mathematically equivalent solutions to the MO problem. However, interesting design solutions can be identified subjectively, e.g., the ellipsoid with a major axis of 720 nm and an aspect ratio of 7.45, as the solution closest to the utopia point. The MO problem formulation is then extended to optimize NP biochemical properties: ligand–receptor binding affinity and ligand density. Optimizing physical and chemical properties simultaneously results in optimal designs with reduced NP sizes and thus enhanced cellular uptake. The presented study provides an insight into NP structures that have potential for producing desirable drug delivery.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041003-041003-9. doi:10.1115/1.4038885.

The blood flow patterns in the region around the aortic valve depend on the geometry of the aorta and on the complex flow–structure interaction between the pulsatile flow and the valve leaflets. Consequently, the flow depends strongly on the constitutive properties of the tissue, which can be expected to vary between healthy and diseased heart valves or native and prosthetic valves. The main goal of this work is to qualitatively demonstrate that the choice of the constitutive model of the aortic valve is critical in analysis of heart hemodynamics. To accomplish that two different constitutive models were used in curvilinear immersed boundary–finite element–fluid–structure interaction (CURVIB-FE-FSI) method developed by Gilmanov et al. (2015, “A Numerical Approach for Simulating Fluid Structure Interaction of Flexible Thin Shells Undergoing Arbitrarily Large Deformations in Complex Domains,” J. Comput. Phys., 300, pp. 814–843.) to simulate an aortic valve in an anatomic aorta at physiologic conditions. The two constitutive models are: (1) the Saint-Venant (StV) model and (2) the modified May-Newman&Yin (MNY) model. The MNY model is more general and includes nonlinear, anisotropic effects. It is appropriate to model the behavior of both prosthetic and biological tissue including native valves. Both models are employed to carry out FSI simulations of the same valve in the same aorta anatomy. The computed results reveal dramatic differences in both the vorticity dynamics in the aortic sinus and the wall shear-stress patterns on the aortic valve leaflets and underscore the importance of tissue constitutive models for clinically relevant simulations of aortic valves.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041004-041004-13. doi:10.1115/1.4038250.

This paper reports on a new boundary condition formulation to model the total coronary myocardial flow and resistance characteristics of the myocardial vascular bed for any specific patient when considered for noninvasive diagnosis of ischemia. The developed boundary condition model gives an implicit representation of the downstream truncated coronary bed. Further, it is based on incorporating patient-specific physiological parameters that can be noninvasively extracted to account for blood flow demand to the myocardium at rest and hyperemic conditions. The model is coupled to a steady three-dimensional (3D) collocated pressure-based finite volume flow solver and used to characterize the “functional significance” of a patient diseased coronary artery segment without the need for predicting the hemodynamics of the entire arterial system. Predictions generated with this boundary condition provide a deep understanding of the inherent challenges behind noninvasive image-based diagnostic techniques when applied to human diseased coronary arteries. The overall numerical method and formulated boundary condition model are validated via two computational-based procedures and benchmarked with available measured data. The newly developed boundary condition is used via a designed computational methodology to (a) confirm the need for incorporating patient-specific physiological parameters when modeling the downstream coronary resistance, (b) explain the discrepancies presented in the literature between measured and computed fractional flow reserve (FFRCT), and (c) discuss the current limitations and future challenges in shifting to noninvasive assessment of ischemia.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041005-041005-12. doi:10.1115/1.4038263.

Accurate cap thickness and stress/strain quantifications are of fundamental importance for vulnerable plaque research. Virtual histology intravascular ultrasound (VH-IVUS) sets cap thickness to zero when cap is under resolution limit and IVUS does not see it. An innovative modeling approach combining IVUS and optical coherence tomography (OCT) is introduced for cap thickness quantification and more accurate cap stress/strain calculations. In vivo IVUS and OCT coronary plaque data were acquired with informed consent obtained. IVUS and OCT images were merged to form the IVUS + OCT data set, with biplane angiography providing three-dimensional (3D) vessel curvature. For components where VH-IVUS set zero cap thickness (i.e., no cap), a cap was added with minimum cap thickness set as 50 and 180 μm to generate IVUS50 and IVUS180 data sets for model construction, respectively. 3D fluid–structure interaction (FSI) models based on IVUS + OCT, IVUS50, and IVUS180 data sets were constructed to investigate cap thickness impact on stress/strain calculations. Compared to IVUS + OCT, IVUS50 underestimated mean cap thickness (27 slices) by 34.5%, overestimated mean cap stress by 45.8%, (96.4 versus 66.1 kPa). IVUS50 maximum cap stress was 59.2% higher than that from IVUS + OCT model (564.2 versus 354.5 kPa). Differences between IVUS and IVUS + OCT models for cap strain and flow shear stress (FSS) were modest (cap strain <12%; FSS <6%). IVUS + OCT data and models could provide more accurate cap thickness and stress/strain calculations which will serve as basis for further plaque investigations.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041006-041006-10. doi:10.1115/1.4038747.

Methods that effectively assess and train dynamic seated balance are critical for enhancing functional independence and reducing risk of secondary health complications in the elderly and individuals with neuromuscular impairments. The objective of this research was to devise and validate a portable tool for assessing and training dynamic seated balance. An instrumented wobble board was designed and constructed that (1) elicits multidirectional perturbations in seated individuals, (2) quantifies seated balance proficiency, and (3) provides real-time, kinematics-based vibrotactile feedback. After performing a technical validation study to compare kinematic wobble board measurements against a gold-standard motion capture system, 15 nondisabled participants performed a dynamic sitting task using the wobble board. Our results demonstrate that the tilt angle measurements were highly accurate throughout the range of wobble board dynamics. Furthermore, the posturographic analyses for the dynamic sitting task revealed that the wobble board can effectively discriminate between the different conditions of perturbed balance, demonstrating its potential to serve as a clinical tool for the assessment and training of seated balance. Vibrotactile feedback decreased the variance of wobble board tilt, demonstrating its potential for use as a balance training tool. Unlike similar instrumented tools, the wobble board is portable, requires no laboratory equipment, and can be adjusted to meet the user's balance abilities. While future work is warranted, obtained findings will aid in effective translation of assessment and training techniques to a clinical setting, which has the potential to enhance the diagnosis and prognosis for individuals with seated balance impairments.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041007-041007-9. doi:10.1115/1.4038897.

Previous two-dimensional (2D) studies have shown that there is a spectrum of carpal mechanics that varies between row-type motion and column-type motion as a function of wrist laxity. More recent three-dimensional (3D) studies have suggested instead that carpal bone motion is consistent across individuals. The purpose of this study was to use 3D methods to determine whether carpal kinematics differ between stiffer wrists and wrists with higher laxity. Wrist laxity was quantified using a goniometer in ten subjects by measuring passive wrist flexion–extension (FE) range of motion (ROM). In vivo kinematics of subjects' scaphoid and lunate with respect to the radius were computed from computed tomography (CT) volume images in wrist radial and ulnar deviation positions. Scaphoid and lunate motion was defined as “column-type” if the bones flexed and extended during wrist radial–ulnar deviation (RUD), and “row-type” if the bones radial–ulnar deviated during wrist RUD. We found that through wrist RUD, the scaphoid primarily flexed and extended, but the scaphoids of subjects with decreased laxity had a larger component of RUD (R2 = 0.48, P < 0.05). We also determined that the posture of the scaphoid in the neutral wrist position predicts wrist radial deviation (RD) ROM (R2 = 0.46, P < 0.05). These results suggest that ligament laxity plays a role in affecting carpal bone motion of the proximal row throughout radial and ulnar deviation motions; however, other factors such as bone position may also affect motion. By developing a better understanding of normal carpal kinematics and how they are affected, this will help physicians provide patient-specific approaches to different wrist pathologies.

Topics: Kinematics , Bone , Rotation
Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041008-041008-11. doi:10.1115/1.4038330.

The objective of the study was to investigate the effects of bariatric surgery-induced weight loss on knee gait and cartilage degeneration in osteoarthritis (OA) by combining magnetic resonance imaging (MRI), gait analysis, finite element (FE) modeling, and cartilage degeneration algorithm. Gait analyses were performed for obese subjects before and one-year after the bariatric surgery. FE models were created before and after weight loss for those subjects who did not have severe tibio-femoral knee cartilage loss. Knee cartilage degenerations were predicted using an adaptive cartilage degeneration algorithm which is based on cumulative overloading of cartilage, leading to iteratively altered cartilage properties during OA. The average weight loss was 25.7±11.0 kg corresponding to a 9.2±3.9 kg/m2 decrease in body mass index (BMI). External knee rotation moment increased, and minimum knee flexion angle decreased significantly (p < 0.05) after weight loss. Moreover, weight loss decreased maximum cartilage degeneration by 5±23% and 13±11% on the medial and lateral tibial cartilage surfaces, respectively. Average degenerated volumes in the medial and lateral tibial cartilage decreased by 3±31% and 7±32%, respectively, after weight loss. However, increased degeneration levels could also be observed due to altered knee kinetics. The present results suggest that moderate weight loss changes knee kinetics and kinematics and can slow-down cartilage degeneration for certain patients. Simulation results also suggest that prediction of cartilage degeneration is subject-specific and highly depend on the altered gait loading, not just the patient's weight.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041009-041009-8. doi:10.1115/1.4038200.

Finite element human body models (FEHBMs) are nowadays commonly used to simulate pre- and in-crash occupant response in order to develop advanced safety systems. In this study, a biofidelic model for adipose tissue is developed for this application. It is a nonlinear viscoelastic model based on the Reese et al.'s formulation. The model is formulated in a large strain framework and applied for finite element (FE) simulation of two types of experiments: rheological experiments and ramped-displacement experiments. The adipose tissue behavior in both experiments is represented well by this model. It indicates the capability of the model to be used in large deformation and wide range of strain rates for application in human body models.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041010-041010-14. doi:10.1115/1.4038886.

Contrast ultrasound is a widely used clinical tool to obtain real-time qualitative blood flow assessments in the heart, liver, etc. Echocardiographic particle image velocimetry (echo-PIV) is a technique for obtaining quantitative velocity maps from contrast ultrasound images. However, unlike optical particle image velocimetry (PIV), routine echo images are prone to nonuniform spatiotemporal variations in tracer distribution, making analysis difficult for standard PIV algorithms. This study introduces optimized procedures that integrate image enhancement, PIV, and particle tracking velocimetry (PTV) to obtain reliable time-resolved two-dimensional (2D) velocity distributions. During initial PIV analysis, multiple results are obtained by varying processing parameters. Optimization involving outlier removal and smoothing is used to select the correct vector. These results are used in a multiparameter PTV procedure. To demonstrate their clinical value, the procedures are implemented to obtain velocity and vorticity distributions over multiple cardiac cycles using images acquired from four left ventricular thrombus (LVT) patients. Phase-averaged data elucidate flow structure evolution over the cycle and are used to calculate penetration depth and strength of left ventricular (LV) vortices, as well as apical velocity induced by them. The present data are consistent with previous time-averaged results for the minimum vortex penetration depth associated with LVT occurrence. However, due to decay and fragmentation of LV vortices, as they migrate away from the mitral annulus, in two cases with high penetration, there is still poor washing near the resolved clot throughout the cycle. Hence, direct examination of entire flow evolution may be useful for assessing risk of LVT relapse before prescribing anticoagulants.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041011-041011-11. doi:10.1115/1.4038744.

The extracellular matrix provides macroscale structure to tissues and microscale guidance for cell contraction, adhesion, and migration. The matrix is composed of a network of fibers, which each deform by stretching, bending, and buckling. Whereas the mechanics has been well characterized in uniform shear and extension, the response to more general loading conditions remains less clear, because the associated displacement fields cannot be predicted a priori. Studies simulating contraction, such as due to a cell, have observed displacements that propagate over a long range, suggesting mechanisms such as reorientation of fibers toward directions of tensile force and nonlinearity due to buckling of fibers under compression. It remains unclear which of these two mechanisms produces the long-range displacements and how properties like fiber bending stiffness and fiber length affect the displacement field. Here, we simulate contraction of an inclusion within a fibrous network and fit the resulting radial displacements to ur ∼ rn where the power n quantifies the decay of displacements over distance, and a value of n less than that predicted by classical linear elasticity indicates displacements that propagate over a long range. We observed displacements to propagate over a longer range for greater contraction of the inclusion, for networks having longer fibers, and for networks with lower fiber bending stiffness. Contraction of the inclusion also caused fibers to reorient into the radial direction, but, surprisingly, the reorientation was minimally affected by bending stiffness. We conclude that both reorientation and nonlinearity are responsible for the long-range displacements.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041012-041012-8. doi:10.1115/1.4038887.

Elastin is a peculiar elastomer in that it requires water to maintain resilience, and its mechanical properties are closely associated with the immediate aqueous environment. The bulk, extra- and intrafibrillar water plays important roles in both elastic and viscoelastic properties of elastin. In this study, a two-stage liquid–vapor method was developed to investigate the effects of water loss on the mechanical properties of porcine aortic elastin. The tissue samples started in a phosphate-buffered saline (PBS) solution at their fully hydrated condition, with a gravimetric water content of 370±36%. The hydration level was reduced by enclosing the tissue in dialysis tubing and submerging it in polyethylene glycol (PEG) solution at concentrations of 10%, 20%, 30%, and 45% w/v, which reduced the water content of the samples to 258±34%, 224±20%, 109±9%, and 58±3%, respectively. The samples were then transferred to a humidity chamber to maintain the hydration level while the samples underwent equi-biaxial tensile and stress relaxation tests. The concentration of 10% PEG treatment induced insignificant changes in tissue dimensions and stiffness, indicating that the removal of bulk water has less effect on elastin. Significant increases in tangent modulus were observed after 20% and 30% PEG treatment due to the decreased presence of extrafibrillar water. Elastin treated with 45% PEG shows a very rigid behavior as most of the extrafibrillar water is eliminated. These results suggest that extrafibrillar water is crucial for elastin to maintain its elastic behavior. It was also observed that the anisotropy of elastin tends to decrease with water loss. An increase in stress relaxation was observed for elastin treated with 30% PEG, indicating a more viscous behavior of elastin when the amount of extrafibrillar water is significantly reduced. Results from this study shed light on the close association between the bulk, extra- and intrafibrillar water pools and the mechanics of elastin.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2018;140(4):041013-041013-8. doi:10.1115/1.4039150.

Aneurysm recurrence is the most critical concern following coil embolization of a cerebral aneurysm. Adequate packing density (PD) and coil uniformity are believed necessary to achieve sufficient flow stagnation, which decreases the risk of aneurysm recurrence. The effect of coil distribution on the extent of flow stagnation, however, especially in cases of dense packing (high PD), has received less attention. Thus, the cause of aneurysm recurrence despite dense packing is still an open question. The primary aim of this study is to evaluate the effect of local coil density on the extent of blood flow stagnation in densely coiled aneurysms. For this purpose, we developed a robust computational framework to determine blood flow using a Cartesian grid method, by which the complex fluid pathways in coiled aneurysms could be flexibly treated using an implicit function. This tool allowed us to conduct blood flow analyses in two patient-specific geometries with 50 coil distribution patterns in each aneurysm at clinically adequate PD. The results demonstrated that dense packing in the aneurysm may not necessarily block completely the inflow into the aneurysm and local flow that formed in the neck region, whose strength was inversely related to this local PD. This finding suggests that local coil density in the neck region still plays an important role in disturbing the remaining local flow, which possibly prevents thrombus formation in a whole aneurysm sac, increasing the risk of aneurysm regrowth and subsequent recurrence.

Commentary by Dr. Valentin Fuster

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