Adaptive Surrogate Modeling for Efficient Coupling of Musculoskeletal Control and Tissue Deformation Models

Background Finite element (FE) modeling and multibody dynamics have traditionally been applied separately to the domains of tissue mechanics and musculoskeletal movements, respectively. Simultaneous simulation of both domains is needed when interactions between tissue and movement are of interest, but this has remained largely impractical due to high computational cost. Method of Approach Here we present a method for concurrent simulation of tissue and movement, in which state of the art methods are used in each domain, and communication occurs via a surrogate modeling system based on locally weighted regression. The surrogate model only performs FE simulations when regression from previous results is not within a user-specified tolerance. For proof of concept and to illustrate feasibility, the methods were demonstrated on an optimization of jumping movement using a planar musculoskeletal model coupled to a FE model of the foot. To test the relative accuracy of the surrogate model outputs against those of the FE model, a single forward dynamics simulation was performed with FE calls at every integration step and compared with a corresponding simulation with the surrogate model included. Neural excitations obtained from the jump height optimization were used for this purpose and root mean square (RMS) difference between surrogate and FE model outputs (ankle force and moment, peak contact pressure and peak von Mises stress) were calculated. Results Optimization of jump height required 1800 iterations of the movement simulation, each requiring thousands of time steps. The surrogate modeling system only used the FE model in 5% of time steps, i.e. a 95% reduction of computation time. Errors introduced by the surrogate model were less than 1 mm in jump height and RMS errors of less than 2 N in ground reaction force, 0.25 Nm in ankle moment, and 10 kPa in peak tissue stress. Conclusion Adaptive surrogate modeling based on local regression allows efficient concurrent simulations of tissue mechanics and musculoskeletal movement

Concurrent Muscoskeletal Dynamics and Finite Element Analysis Predicts Altered Gait Patterns to Reduce Foot Tissue Loading

Current computational methods for simulating locomotion have primarily used muscle-driven multibody dynamics, in which neuromuscular control is optimized. Such simulations generally represent joints and soft tissue as simple kinematic or elastic elements for computational efficiency. These assumptions limit application in studies such as ligament injury or osteoarthritis, where local tissue loading must be predicted. Conversely, tissue can be simulated using the finite element method with assumed or measured boundary conditions, but this does not represent the effects of whole body dynamics and neuromuscular control. Coupling the two domains would overcome these limitations and allow prediction of movement strategies guided by tissue stresses. Here we demonstrate this concept in a gait simulation where a musculoskeletal model is coupled to a finite element representation of the foot. Predictive simulations incorporated peak plantar tissue deformation into the objective of the movement optimization, as well as terms to track normative gait data and minimize fatigue. Two optimizations were performed, first without the strain minimization term and second with the term. Convergence to realistic gait patterns was achieved with the second optimization realizing a 44% reduction in peak tissue strain energy density. The study demonstrated that it is possible to alter computationally predicted neuromuscular control to minimize tissue strain while including desired kinematic and muscular behavior. Future work should include experimental validation before application of the methodology to patient care

Adaptive Surrogate Modeling for Efficient Coupling of Musculoskeletal Control and Tissue Deformation Models

Background Finite element (FE) modeling and multibody dynamics have traditionally been applied separately to the domains of tissue mechanics and musculoskeletal movements, respectively. Simultaneous simulation of both domains is needed when interactions between tissue and movement are of interest, but this has remained largely impractical due to high computational cost. Method of Approach Here we present a method for concurrent simulation of tissue and movement, in which state of the art methods are used in each domain, and communication occurs via a surrogate modeling system based on locally weighted regression. The surrogate model only performs FE simulations when regression from previous results is not within a user-specified tolerance. For proof of concept and to illustrate feasibility, the methods were demonstrated on an optimization of jumping movement using a planar musculoskeletal model coupled to a FE model of the foot. To test the relative accuracy of the surrogate model outputs against those of the FE model, a single forward dynamics simulation was performed with FE calls at every integration step and compared with a corresponding simulation with the surrogate model included. Neural excitations obtained from the jump height optimization were used for this purpose and root mean square (RMS) difference between surrogate and FE model outputs (ankle force and moment, peak contact pressure and peak von Mises stress) were calculated. Results Optimization of jump height required 1800 iterations of the movement simulation, each requiring thousands of time steps. The surrogate modeling system only used the FE model in 5% of time steps, i.e. a 95% reduction of computation time. Errors introduced by the surrogate model were less than 1 mm in jump height and RMS errors of less than 2 N in ground reaction force, 0.25 Nm in ankle moment, and 10 kPa in peak tissue stress. Conclusion Adaptive surrogate modeling based on local regression allows efficient concurrent simulations of tissue mechanics and musculoskeletal movement

Concurrent Muscoskeletal Dynamics and Finite Element Analysis Predicts Altered Gait Patterns to Reduce Foot Tissue Loading

Current computational methods for simulating locomotion have primarily used muscle-driven multibody dynamics, in which neuromuscular control is optimized. Such simulations generally represent joints and soft tissue as simple kinematic or elastic elements for computational efficiency. These assumptions limit application in studies such as ligament injury or osteoarthritis, where local tissue loading must be predicted. Conversely, tissue can be simulated using the finite element method with assumed or measured boundary conditions, but this does not represent the effects of whole body dynamics and neuromuscular control. Coupling the two domains would overcome these limitations and allow prediction of movement strategies guided by tissue stresses. Here we demonstrate this concept in a gait simulation where a musculoskeletal model is coupled to a finite element representation of the foot. Predictive simulations incorporated peak plantar tissue deformation into the objective of the movement optimization, as well as terms to track normative gait data and minimize fatigue. Two optimizations were performed, first without the strain minimization term and second with the term. Convergence to realistic gait patterns was achieved with the second optimization realizing a 44% reduction in peak tissue strain energy density. The study demonstrated that it is possible to alter computationally predicted neuromuscular control to minimize tissue strain while including desired kinematic and muscular behavior. Future work should include experimental validation before application of the methodology to patient care

A Three-Dimensional Inverse Finite Element Analysis of the Heel Pad

Quantification of plantar tissue behavior of the heel pad is essential in developing computational models for predictive analysis of preventive treatment options such as footwear for patients with diabetes. Simulation based studies in the past have generally adopted heel pad properties from the literature, in return using heel-specific geometry with material properties of a different heel. In exceptional cases, patient-specific material characterization was performed with simplified two-dimensional models, without further evaluation of a heel-specific response under different loading conditions. The aim of this study was to conduct an inverse finite element analysis of the heel in order to calculate heel-specific material properties in situ. Multidimensional experimental data available from a previous cadaver study by Erdemir (“An Elaborate Data Set Characterizing the Mechanical Response of the Foot,” ASME J. Biomech. Eng., 131 (9), pp. 094502) was used for model development, optimization, and evaluation of material properties. A specimen-specific three-dimensional finite element representation was developed. Heel pad material properties were determined using inverse finite element analysis by fitting the model behavior to the experimental data. Compression dominant loading, applied using a spherical indenter, was used for optimization of the material properties. The optimized material properties were evaluated through simulations representative of a combined loading scenario (compression and anterior-posterior shear) with a spherical indenter and also of a compression dominant loading applied using an elevated platform. Optimized heel pad material coefficients were 0.001084 MPa (μ), 9.780 (α) (with an effective Poisson’s ratio (ν) of 0.475), for a first-order nearly incompressible Ogden material model. The model predicted structural response of the heel pad was in good agreement for both the optimization

An Elaborate Data Set Characterizing the Mechanical Response of the Foot

Mechanical properties of the foot are responsible for its normal function and play a role in various clinical problems. Specifically, we are interested in quantification of foot mechanical properties to assist the development of computational models for movement analysis and detailed simulations of tissue deformation. Current available data are specific to a foot region and the loading scenarios are limited to a single direction. A data set that incorporates regional response, to quantify individual function of foot components, as well as the overall response, to illustrate their combined operation, does not exist. Furthermore, the combined three-dimensional loading scenarios while measuring the complete three-dimensional deformation response are lacking. When combined with an anatomical image data set, development of anatomically realistic and mechanically validated models becomes possible. Therefore, the goal of this study was to record and disseminate the mechanical response of a foot specimen, supported by imaging data. Robotic testing was conducted at the rear foot, forefoot, metatarsal heads, and the foot as a whole. Complex foot deformations were induced by single mode loading, e.g., compression, and combined loading, e.g., compression and shear. Small and large indenters were used for heel and metatarsal head loading, an elevated platform was utilized to isolate the rear foot and forefoot, and a full platform compressed the whole foot. Three-dimensional tool movements and reaction loads were recorded simultaneously. Computed tomography scans of the same specimen were collected for anatomical reconstruction a priori. The three-dimensional mechanical response of the specimen was nonlinear and viscoelastic. A low stiffness region was observed starting with contact between the tool and foot regions, increasing with loading. Loading and unloading responses portrayed hysteresis. Loading range ensured capturing the toe and linear regions of the load deformation curves for the dominant loading direction, with the rates approximating those of walking. A large data set was successfully obtained to characterize the overall and the regional mechanical responses of an intact foot specimen under single and combined loads. Medical imaging complemented the mechanical testing data to establish the potential relationship between the anatomical architecture and mechanical responses and to further develop foot models that are mechanically realistic and anatomically consistent. This combined data set has been documented and disseminated in the public domain to promote future development in foot biomechanics

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Snehal Chokhandre A Three-Dimensional Inverse Finite Element Analysis of the Heel Pad

Quantification of plantar tissue behavior of the heel pad is essential in developing computational models for predictive analysis of preventive treatment options such as footwear for patients with diabetes. Simulation based studies in the past have generally adopted heel pad properties from the literature, in return using heel-specific geometry with material properties of a different heel. In exceptional cases, patient-specific material characterization was performed with simplified two-dimensional models, without further evaluation of a heel-specific response under different loading conditions. The aim of this study was to conduct an inverse finite element analysis of the heel in order to calculate heel-specific material properties in situ. Multidimensional experimental data available from a previous cadaver study by Erdemir et al. ("An Elaborate Data Set Characterizing the Mechanical Response of the Foot," ASME J. Biomech. Eng., 131(9), pp. 094502) was used for model development, optimization, and evaluation of material properties. A specimen-specific three-dimensional finite element representation was developed. Heel pad material properties were determined using inverse finite element analysis by fitting the model behavior to the experimental data. Compression dominant loading, applied using a spherical indenter, was used for optimization of the material properties. The optimized material properties were evaluated through simulations representative of a combined loading scenario (compression and anterior-posterior shear) with a spherical indenter and also of a compression dominant loading applied using an elevated platform. Optimized heel pad material coefficients were 0.001084 MPa (l), 9.780 (a) (with an effective Poisson's ratio () of 0.475), for a first-order nearly incompressible Ogden material model. The model predicted structural response of the heel pad was in good agreement for both the optimization (<1.05% maximum tool force, 0.9% maximum tool displacement) and validation cases (6.5% maximum tool force, 15% maximum tool displacement). The inverse analysis successfully predicted the material properties for the given specimen-specific heel pad using the experimental data for the specimen. The modeling framework and results can be used for accurate predictions of the threedimensional interaction of the heel pad with its surroundings