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IN THIS ISSUE

### Research Papers

J Biomech Eng. 2019;141(3):031001-031001-10. doi:10.1115/1.4040945.

Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein. Here, we focused on tuberous sclerosis complex (TSC), a genetic disorder with a high penetrance of ASD. We investigated mechanical differences between murine brains obtained from control and TSC cohorts at various deformation length- and time-scales. At the microscale, we conducted creep-compliance and stress relaxation experiments using atomic force microscope(AFM)-enabled indentation. At the mesoscale, we conducted impact indentation using a pendulum-based instrumented indenter to extract mechanical energy dissipation metrics. At the macroscale, we used oscillatory shear rheology to quantify the frequency-dependent shear moduli. Despite significant changes in the cellular organization of TSC brain tissue, we found no corresponding changes in the quantified mechanical properties at every length- and time-scale explored. This investigation of the mechanical characteristics of the brain has broadened our understanding of causes and markers of TSC/ASD, while raising questions about whether any mechanical differences can be detected in other animal models of ASD or other disease models that also feature abnormal brain structure.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031002-031002-8. doi:10.1115/1.4042181.

Several approaches (anterior, posterior, lateral, and transforaminal) are used in lumbar fusion surgery. However, it is unclear whether one of these approaches has the greatest subsidence risk as published clinical rates of cage subsidence vary widely (7–70%). Specifically, there is limited data on how a patient's endplate morphometry and trabecular bone quality influences cage subsidence risk. Therefore, this study compared subsidence (stiffness, maximum force, and work) between anterior (ALIF), lateral (LLIF), posterior (PLIF), and transforaminal (TLIF) lumbar interbody fusion cage designs to understand the impact of endplate and trabecular bone quality on subsidence. Forty-eight lumbar vertebrae were imaged with micro-ct to assess trabecular microarchitecture. micro-ct images of each vertebra were then imported into image processing software to measure endplate thickness (ET) and maximum endplate concavity depth (ECD). Generic ALIF, LLIF, PLIF, and TLIF cages made of polyether ether ketone were implanted on the superior endplates of all vertebrae and subsidence testing was performed. The results indicated that TLIF cages had significantly lower (p < 0.01) subsidence stiffness and maximum subsidence force compared to ALIF and LLIF cages. For all cage groups, trabecular bone volume fraction was better correlated with maximum subsidence force compared to ET and concavity depth. These findings highlight the importance of cage design (e.g., surface area), placement on the endplate, and trabecular bone quality on subsidence. These results may help surgeons during cage selection for lumbar fusion procedures to mitigate adverse events such as cage subsidence.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031003-031003-12. doi:10.1115/1.4042183.

Mathematical models of the human spine can be used to investigate spinal biomechanics without the difficulties, limitations, and ethical concerns associated with physical experimentation. Validation of such models is necessary to ensure that the modeled system behavior accurately represents the physics of the actual system. The goal of this work was to validate a medical image-based nonlinear lumbosacral spine finite element model of a healthy 20-yr-old female subject under physiological moments. Range of motion (ROM), facet joint forces (FJF), and intradiscal pressure (IDP) were compared with experimental values and validated finite element models from the literature. The finite element model presented in this work was in good agreement with published experimental studies and finite element models under pure moments. For applied moments of 7.5 N·m, the ROM in flexion–extension, axial rotation, and lateral bending were 39 deg, 16 deg, and 28 deg, respectively. Excellent agreement was observed between the finite element model and experimental data for IDP under pure compressive loading. The predicted FJFs were lower than those of the experimental results and validated finite element models for extension and torsion, likely due to the nondegenerate properties chosen for the intervertebral disks and morphology of the young female spine. This work is the first to validate a computational lumbar spine model of a young female subject. This model will serve as a valuable tool for predicting orthopedic spinal injuries, studying the effect of intervertebral disk replacements using advanced biomaterials, and investigating soft tissue degeneration.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031004-031004-9. doi:10.1115/1.4041906.

The use of anthropomorphic test devices (ATDs) for calculating injury risk of occupants in spaceflight scenarios is crucial for ensuring the safety of crewmembers. Finite element (FE) modeling of ATDs reduces cost and time in the design process. The objective of this study was to validate a Hybrid III ATD FE model using a multidirection test matrix for future spaceflight configurations. Twenty-five Hybrid III physical tests were simulated using a 50th percentile male Hybrid III FE model. The sled acceleration pulses were approximately half-sine shaped, and can be described as a combination of peak acceleration and time to reach peak (rise time). The range of peak accelerations was 10–20 G, and the rise times were 30–110 ms. Test directions were frontal (−GX), rear (GX), vertical (GZ), and lateral (GY). Simulation responses were compared to physical tests using the correlation and analysis (CORA) method. Correlations were very good to excellent and the order of best average response by direction was −GX (0.916±0.054), GZ (0.841±0.117), GX (0.792±0.145), and finally GY (0.775±0.078). Qualitative and quantitative results demonstrated the model replicated the physical ATD well and can be used for future spaceflight configuration modeling and simulation.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031005-031005-11. doi:10.1115/1.4042184.

The efficacy of reduced order modeling for transstenotic pressure drop in the coronary arteries is presented. Coronary artery disease is a leading cause of death worldwide and the computation of pressure drop in the coronary arteries has become a standard for evaluating the functional significance of a coronary stenosis. Comprehensive models typically employ three-dimensional (3D) computational fluid dynamics (CFD) to simulate coronary blood flow in order to compute transstenotic pressure drop at the arterial stenosis. In this study, we evaluate the capability of different hydrodynamic models to compute transstenotic pressure drop. Models range from algebraic formulae to one-dimensional (1D), two-dimensional (2D), and 3D time-dependent CFD simulations. Although several algebraic pressure-drop formulae have been proposed in the literature, these models were found to exhibit wide variation in predictions. Nonetheless, we demonstrate an algebraic formula that provides consistent predictions with 3D CFD results for various changes in stenosis severity, morphology, location, and flow rate. The accounting of viscous dissipation and flow separation were found to be significant contributions to accurate reduce order modeling of transstenotic coronary hemodynamics.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031006-031006-9. doi:10.1115/1.4041905.

Modeling of intracellular processes occurring during the development of Alzheimer's disease (AD) can be instrumental in understanding the disease and can potentially contribute to finding treatments for the disease. The model of intracellular processes in AD, which we previously developed, contains a large number of parameters. To distinguish between more important and less important parameters, we performed a local sensitivity analysis of this model around the values of parameters that give the best fit with published experimental results. We show that the influence of model parameters on the total concentrations of amyloid precursor protein (APP) and tubulin-associated unit (tau) protein in the axon is reciprocal to the influence of the same parameters on the average velocities of the same proteins during their transport in the axon. The results of our analysis also suggest that in the beginning of AD the aggregation of amyloid-β and misfolded tau protein have little effect on transport of APP and tau in the axon, which suggests that early damage in AD may be reversible.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031007-031007-11. doi:10.1115/1.4042179.

In a prior study, we proposed a novel monopolar expandable electrode (MEE) for use in radiofrequency ablation (RFA). The purpose of our work was to now validate and evaluate this electrode using on in vitro experimental model and computer simulation. Two commercially available RF electrodes (conventional electrode (CE) and umbrella electrode (UE)) were used to compare the ablation results with the novel MEE using an in vitro egg white model and in vivo liver tumor model to verify the efficacy of MEE in the large tumor ablation, respectively. The sharp increase in impedance during RFA procedures was taken as the termination of RFA protocols. In the in vitro egg white experiment, the ablation volume of MEE, CE, and UE was 75.3$±$1.6 cm3, 2.7$±$0.4 cm3, and 12.4$±$1.8 cm3 (P < 0.001), respectively. Correspondingly, the sphericity was 88.1$±$0.9%, 12.9$±$1.3%, and 62.0$±$3.0% (P < 0.001), respectively. A similar result was obtained in the in vitro egg white computer simulation. In the liver tumor computer simulation, the volume and sphericity of ablation zone generated by MEE, CE, and UE were 36.6 cm3 and 93.6%, 3.82 cm3 and 16.9%, and 13.5 cm3 and 56.7%, respectively. In summary, MEE has the potential to achieve complete ablation in the treatment of large tumors (>3 cm in diameter) compared to CE and UE due to the larger electrode–tissue interface and more round shape of hooks.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031008-031008-10. doi:10.1115/1.4042171.

Vascular smooth muscle cells (VSMCs) can regulate arterial mechanics via contractile activity in response to changing mechanical and chemical signals. Contractility is traditionally evaluated via uniaxial isometric testing of isolated rings despite the in vivo environment being very different. Most blood vessels maintain a locally preferred value of in vivo axial stretch while subjected to changes in distending pressure, but both of these phenomena are obscured in uniaxial isometric testing. Few studies have rigorously analyzed the role of in vivo loading conditions in smooth muscle function. Thus, we evaluated effects of uniaxial versus biaxial deformations on smooth muscle contractility by stimulating two regions of the mouse aorta with different vasoconstrictors using one of three testing protocols: (i) uniaxial isometric testing, (ii) biaxial isometric testing, and (iii) axially isometric plus isobaric testing. Comparison of methods (i) and (ii) revealed increased sensitivity and contractile capacity to potassium chloride and phenylephrine (PE) with biaxial isometric testing, and comparison of methods (ii) and (iii) revealed a further increase in contractile capacity with isometric plus isobaric testing. Importantly, regional differences in estimated in vivo axial stretch suggest locally distinct optimal biaxial configurations for achieving maximal smooth muscle contraction, which can only be revealed with biaxial testing. Such differences highlight the importance of considering in vivo loading and geometric configurations when evaluating smooth muscle function. Given the physiologic relevance of axial extension and luminal pressurization, we submit that, when possible, axially isometric plus isobaric testing should be employed to evaluate vascular smooth muscle contractile function.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031009-031009-12. doi:10.1115/1.4042185.

This paper presents a computational framework for the fast feedback control of musculoskeletal systems using muscle synergies. The proposed motor control framework has a hierarchical structure. A feedback controller at the higher level of hierarchy handles the trajectory planning and error compensation in the task space. This high-level task space controller only deals with the task-related kinematic variables, and thus is computationally efficient. The output of the task space controller is a force vector in the task space, which is fed to the low-level controller to be translated into muscle activity commands. Muscle synergies are employed to make this force-to-activation (F2A) mapping computationally efficient. The explicit relationship between the muscle synergies and task space forces allows for the fast estimation of muscle activations that result in the reference force. The synergy-enabled F2A mapping replaces a computationally heavy nonlinear optimization process by a vector decomposition problem that is solvable in real time. The estimation performance of the F2A mapping is evaluated by comparing the F2A-estimated muscle activities against the measured electromyography (EMG) data. The results show that the F2A algorithm can estimate the muscle activations using only the task-related kinematics/dynamics information with ∼70% accuracy. An example predictive simulation is also presented, and the results show that this feedback motor control framework can control arbitrary movements of a three-dimensional (3D) musculoskeletal arm model quickly and near optimally. It is two orders-of-magnitude faster than the optimal controller, with only 12% increase in muscle activities compared to the optimal. The developed motor control model can be used for real-time near-optimal predictive control of musculoskeletal system dynamics.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031010-031010-10. doi:10.1115/1.4042438.

A spine is proven to be subjected to a follower load which is a compressive load of physiologic magnitude acting on the whole spine. The path of the follower load approximates the tangent to the curve of the spine in in vivo neutral standing posture. However, the specific path location of the follower load is still unclear. The aim of this study is to find out the most realistic location of the follower load path (FLP) for a lumbar spine in standing. A three-dimensional (3D) nonlinear finite element model (FEM) of lumbosacral vertebrae (L1-S1) with consideration of the calibrated material properties was established and validated by comparing with the experimental data. We show that the shape of the lumbosacral spine is strongly affected by the location of FLP. An evident nonlinear relationship between the FLP location and the kinematic response of the L1-S1 lumbosacral spine exists. The FLP at about 4 and 3 mm posterior to the curve connecting the center of the vertebral bodies delivers the most realistic location in standing for healthy people and patients having low back pains (LPBs), respectively. Moreover, the “sweeping” method introduced in this study can be applicable to all individualized FEM to determine the location of FLP.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):031011-031011-9. doi:10.1115/1.4042435.

Cardiovascular diseases (CVD) are the most prevalent cause of death in the Western World, and their prevalence is only expected to rise. Several screening modalities aim at detecting CVD at the early stages. A common target for early screening is common carotid artery (CCA) stiffness, as reflected in the pulse wave velocity (PWV). For assessing the CCA stiffness using ultrasound (US), one-dimensional (1D) measurements along the CCA axis are typically used, ignoring possible boundary conditions of neck anatomy and the US probe itself. In this study, the effect of stresses and deformations induced by the US probe, and the effect of anatomy surrounding CCA on a simulated 1D stiffness measurement (PWVus) is compared with the ground truth stiffness (PWVgt) in 60 finite-element models (FEM) derived from anatomical computed tomography (CT) scans of ten healthy male volunteers. Based on prior knowledge from the literature, and from results in this study, we conclude that it is safe to approximate arterial stiffness using 1D measurements of compliance or pulse wave velocity, regardless of boundary conditions emerging from the anatomy or from the measurement procedure.

Commentary by Dr. Valentin Fuster

### Technical Brief

J Biomech Eng. 2019;141(3):034501-034501-8. doi:10.1115/1.4042172.

An important feature of humeral orthopedic finite element (FE) models is the trabecular stiffness relationship. These relationships depend on the anatomic site from which they are derived; but have not been developed for the humerus. As a consequence, humeral FE modeling relies on relationships for other anatomic sites. The variation in humeral FE outcomes due to the trabecular stiffness relationship is assessed. Stemless arthroplasty FE models were constructed from CT scans of eight humeri. Models were loaded corresponding to 45 deg and 75 deg abduction. Each bone was modeled five times with the only variable being the trabecular stiffness relationship: four derived from different anatomic-sites and one pooled across sites. The FE outcome measures assessed were implant-bone contact percentage, von Mises of the change in stress, and bone response potential. The variance attributed to the selection of the trabecular stiffness relationship was quantified as the standard deviation existing between models of different trabecular stiffness. Overall, variability due to changing the trabecular stiffness relationship was low for all humeral FE outcome measures assessed. The variability was highest within the stress and bone formation potential outcome measures of the trabecular region. Variability only exceeded 10% in the trabecular stress change within two of the eight slices evaluated. In conclusion, the low variations attributable to the selection of a trabecular stiffness relationship based on anatomic-site suggest that FE models constructed for shoulder arthroplasty can utilize an inhomogeneous site-pooled trabecular relationship without inducing marked variability in the assessed outcome measures.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):034502-034502-4. doi:10.1115/1.4042044.

In engineering and medicine, there is a growing interest in using textiles made of composites with enhanced thermal properties. One such type of textile is fabric impregnated with ceramics and mineral particles. This material has high emissivity in the infrared range and may have therapeutic benefits for treatments of diseases, like Raynaud's syndrome. While there is significant clinical and commercial interest, there is an evident lack of fundamental studies on the heat transfer aspects of these fabrics. The goal of this technical brief is to present results from a fundamental study examining the thermal effects of fabric with ceramics and minerals (produced by Nanobionic, Inc., Athens, Greece) on the temperatures of the hands. With a confidence level of 90%, the results show that the textile with ceramics and minerals has an enhanced thermal effect on warming a cold hand in comparison to a placebo fabric without ceramics or minerals. Much more research is needed to increase the level of confidence and develop a fundamental understanding of the mechanism.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2019;141(3):034503-034503-6. doi:10.1115/1.4042436.

In this study, an inverse dynamics optimization formulation and solution procedure is developed for musculoskeletal simulations. The proposed method has three main features: high order recursive B-spline interpolation, partition of unity, and inverse dynamics formulation. First, joint angle and muscle force profiles are represented by recursive B-splines. The formula for high order recursive B-spline derivatives is derived for state variables calculation. Second, partition of unity is used to handle the multicontact indeterminacy between human and environment during the motion. The global forces and moments are distributed to each contacting point through the corresponding partition ratio. Third, joint torques are inversely calculated from equations of motion (EOM) based on state variables and contacts to avoid numerical integration of EOM. Therefore, the design variables for the optimization problem are joint angle control points, muscle force control points, knot vector, and partition ratios for contacting points. The sum of muscle stress/activity squared is minimized as the cost function. The constraints are imposed for human physical constraints and task-based constraints. The proposed formulation is demonstrated by simulating a trajectory planning problem of a planar musculoskeletal arm with six muscles. In addition, the gait motion of a two-dimensional musculoskeletal model with sixteen muscles is also optimized by using the approach developed in this paper. The gait optimal solution is obtained in about 1 min central processing unit (CPU) time. The predicted kinematics, kinetics, and muscle forces have general trends that are similar to those reported in the literature.

Commentary by Dr. Valentin Fuster