NSF DARE-transforming modeling in neurorehabilitation: perspectives and opportunities from US funding agencies.

In recognition of the importance and timeliness of computational models for accelerating progress in neurorehabilitation, the U.S. National Science Foundation (NSF) and the National Institutes of Health (NIH) sponsored a conference in March 2023 at the University of Southern California that drew global participation from engineers, scientists, clinicians, and trainees. This commentary highlights promising applications of computational models to understand neurorehabilitation ("Using computational models to understand complex mechanisms in neurorehabilitation" section), improve rehabilitation care in the context of digital twin frameworks ("Using computational models to improve delivery and implementation of rehabilitation care" section), and empower future interdisciplinary workforces to deliver higher-quality clinical care using computational models ("Using computational models in neurorehabilitation requires an interdisciplinary workforce" section). The authors describe near-term gaps and opportunities, all of which encourage interdisciplinary team science. Four major opportunities were identified including (1) deciphering the relationship between engineering figures of merit-a term commonly used by engineers to objectively quantify the performance of a device, system, method, or material relative to existing state of the art-and clinical outcome measures, (2) validating computational models from engineering and patient perspectives, (3) creating and curating datasets that are made publicly accessible, and (4) developing new transdisciplinary frameworks, theories, and models that incorporate the complexities of the nervous and musculoskeletal systems. This commentary summarizes U.S. funding opportunities by two Federal agencies that support computational research in neurorehabilitation. The NSF has funding programs that support high-risk/high-reward research proposals on computational methods in neurorehabilitation informed by theory- and data-driven approaches. The NIH supports the development of new interventions and therapies for a wide range of nervous system injuries and impairments informed by the field of computational modeling. The conference materials can be found at https://dare2023.usc.edu/ .

Occupant-centric robotic air filtration and planning for classrooms for Safer school reopening amid respiratory pandemics.

Coexisting with the current COVID-19 pandemic is a global reality that comes with unique challenges impacting daily interactions, business, and facility maintenance. A monumental challenge accompanied is continuous and effective disinfection of shared spaces, such as office/school buildings, elevators, classrooms, and cafeterias. Although ultraviolet light and chemical sprays are routines for indoor disinfection, they irritate humans, hence can only be used when the facility is unoccupied. Stationary air filtration systems, while being irritation-free and commonly available, fail to protect all occupants due to limitations in air circulation and diffusion. Hence, we present a novel collaborative robot (cobot) disinfection system equipped with a Bernoulli Air Filtration Module, with a design that minimizes disturbance to the surrounding airflow and maneuverability among occupants for maximum coverage. The influence of robotic air filtration on dosage at neighbors of a coughing source is analyzed with derivations from a Computational Fluid Dynamics (CFD) simulation. Based on the analysis, the novel occupant-centric online rerouting algorithm decides the path of the robot. The rerouting ensures effective air filtration that minimizes the risk of occupants under their detected layout. The proposed system was tested on a 2 × 3 seating grid (empty seats allowed) in a classroom, and the worst-case dosage for all occupants was chosen as the metric. The system reduced the worst-case dosage among all occupants by 26% and 19% compared to a stationary air filtration system with the same flow rate, and a robotic air filtration system that traverses all the seats but without occupant-centric planning of its path, respectively. Hence, we validated the effectiveness of the proposed robotic air filtration system.

Modeling of slightly-compressible isentropic flows and its compressibility effects on fluid-structure interactions.

In this study, an aeroacoustic fluid model for slightly-compressible isentropic flows is developed and evaluated for its compressibility effects in the context of fluid-structure interactions. This model considers computational feasibility and accuracy by adding compressibility terms directly on the incompressible form of Navier-Stokes equation. Rather than solving for the full compressible form, our slightly-compressible form significantly reduces the complications in establishing stabilization and implementation of its finite element procedure, and yet still captures the fluctuating acoustic waves expected in the compressible form. Using this approach, we demonstrate that generations and propagations of acoustic waves can be accurately captured, without the inclusion of a fully compressible representation of the fluid. Upon the successful verification of its accuracy against analytical and known solutions, we then evaluate the fluid compressibility effect on fluid-structure interactions. Our results show that comparing to an incompressible fluid, a deformable solid generates sound waves while it is driven by the flow and vibrates in the fluid. A periodic volume change in the fluid is also observed, which can be considered as a sound source.

Image-Based Flow Simulations of Pre- and Post-left Atrial Appendage Closure in the Left Atrium.

PURPOSE: For patients with atrial fibrillation, the left atrial appendage (LAA) is often the site of thrombus formation due to low atrial ejection fraction that triggers strokes and other thromboembolic events. Recently introduced percutaneous LAA occlusion procedure is known to reduce LAA-induced strokes. Despite having the procedure, there are still 11% of the patients who continue to suffer from future strokes or transient ischemic attacks, not accounting for the procedural related complications. The high failure rate is largely due to the variabilities in LAA's shape, size, and contractility which may result in ineffectiveness of this procedure. To correctly identify the candidates and evaluate the effectiveness of the procedure, we rely on patient-specific CT scans which provides the exact LA and LAA geometries and predictive hemodynamic analysis to assist in evaluating quantitative flow parameters pre- and post-LAA occlusion procedures. Hemodynamic parameters are critical to predict adverse hemodynamic flow patterns in LAA as well as the effectiveness of LAA closure in individual patient. The aim of this paper is to establish an image-based patient-specific computational fluid dynamic (CFD) simulation framework specific to the prediction of treatment outcomes of LAA closure with atrial fibrillation. This framework utilizes automated LA/LAA image segmentation which yields significant reduction in image processing. One set of patient data with successful procedure outcome is used to illustrate the potential of the proposed framework. METHODS: The proposed LAA occlusion simulation framework is composed of several components: (1) a novel image segmentation procedure, which is fully-automated to identify LA/LAA geometries from CT images, (2) a finite-element mesh generation procedure which transforms the surface geometry into a 3-D volume mesh and properly identified boundary planes, (3) performing CFD simulations with atrial fibrillation flow boundary conditions, and (4) analyzing flow characteristics (velocity, flow patterns, streamlines, vortices) within the LA for before and after LAA closure. RESULTS: Based on the LA/LAA segmentation of a 65 year old female patient with chronic atrial fibrillation, a CFD analysis was pursued to examine flow characteristics upon LAA closure. The results showed that the flow velocity magnitudes were significantly reduced by a maximum factor of 2.21, flow streamlines were greatly stabilized, and mitral outflow appeared to be more organized. Vortices were dramatically reduced in size, number, intensity, as well as duration. During diastole, the peak vortex diameter was reduced from 2.8 to 1.5 cm, while the vortex duration was reduced from 0.210 to 0.135 s. These flow characteristics all indicated a reduced risk in future thrombus formation and strokes based on the established relationship between flow and thrombus formation. For the patient case under study, the effectiveness of the procedure is predicted and found to be consistent with the actual procedural outcome. CONCLUSIONS: This framework successfully predicted patient-specific outcome of a LAA closure procedure for one patient with atrial fibrillation. It can be further developed into a useful tool for pre-procedural planning and candidate selection. More patient data are necessary for further validation studies.

Microfluidics-enabled orientation and microstructure control of macroscopic graphene fibres.

Macroscopic graphene structures such as graphene papers and fibres can be manufactured from individual two-dimensional graphene oxide sheets by a fluidics-enabled assembling process. However, achieving high thermal-mechanical and electrical properties is still challenging due to non-optimized microstructures and morphology. Here, we report graphene structures with tunable graphene sheet alignment and orientation, obtained via microfluidic design, enabling strong size and geometry confinements and control over flow patterns. Thin flat channels can be used to fabricate macroscopic graphene structures with perfectly stacked sheets that exhibit superior thermal and electrical conductivities and improved mechanical strength. We attribute the observed shape and size confinements to the flat distribution of shear stress from the anisotropic microchannel walls and the enhanced shear thinning degree of large graphene oxide sheets in solution. Elongational and step expansion flows are created to produce large-scale graphene tubes and rods with horizontally and perpendicularly aligned graphene sheets by tuning the elongational and extensional shear rates, respectively.

OpenIFEM: A High Performance Modular Open-Source Software of the Immersed Finite Element Method for Fluid-Structure Interactions.

We present a high performance modularly-built open-source software - OpenIFEM. OpenIFEM is a C++ implementation of the modified immersed finite element method (mIFEM) to solve fluid-structure interaction (FSI) problems. This software is modularly built to perform multiple tasks including fluid dynamics (incompressible and slightly compressible fluid models), linear and nonlinear solid mechanics, and fully coupled fluid-structure interactions. Most of open-source software packages are restricted to certain discretization methods; some are under-tested, under-documented, and lack modularity as well as extensibility. OpenIFEM is designed and built to include a set of generic classes for users to adapt so that any fluid and solid solvers can be coupled through the FSI algorithm. In addition, the package utilizes well-developed and tested libraries. It also comes with standard test cases that serve as software and algorithm validation. The software can be built on cross-platform, i.e., Linux, Windows, and Mac OS, using CMake. Efficient parallelization is also implemented for high-performance computing for large-sized problems. OpenIFEM is documented using Doxygen and publicly available to download on GitHub. It is expected to benefit the future development of FSI algorithms and be applied to a variety of FSI applications.

The Perfectly Matched Layer absorbing boundary for fluid-structure interactions using the Immersed Finite Element Method.

In this work, a non-reflective boundary condition, the Perfectly Matched Layer (PML) technique, is adapted and implemented in a fluid-structure interaction numerical framework to demonstrate that proper boundary conditions are not only necessary to capture correct wave propagations in a flow field, but also its interacted solid behavior and responses. While most research on the topics of the non-reflective boundary conditions are focused on fluids, little effort has been done in a fluid-structure interaction setting. In this study, the effectiveness of the PML is closely examined in both pure fluid and fluid-structure interaction settings upon incorporating the PML algorithm in a fully-coupled fluid-structure interaction framework, the Immersed Finite Element Method. The performance of the PML boundary condition is evaluated and compared to reference solutions with a variety of benchmark test cases including known and expected solutions of aeroacoustic wave propagation as well as vortex shedding and advection. The application of the PML in numerical simulations of fluid-structure interaction is then investigated to demonstrate the efficacy and necessity of such boundary treatment in order to capture the correct solid deformation and flow field without the requirement of a significantly large computational domain.

A General Approach to Derive Stress and Elasticity Tensors for Hyperelastic Isotropic and Anisotropic Biomaterials.

Hyperelastic models are of particular interest in modeling biomaterials. In order to implement them, one must derive the stress and elasticity tensors from the given potential energy function explicitly. However, it is often cumbersome to do so because researchers in biomechanics may not be well-exposed to systematic approaches to derive the stress and elasticity tensors as it is vaguely addressed in literature. To resolve this, we present a framework of a general approach to derive the stress and elasticity tensors for hyperelastic models. Throughout the derivation we carefully elaborate the differences between formulas used in the displacement-based formulation and the displacement/pressure mixed formulation. Three hyperelastic models, Mooney-Rivlin, Yeoh and Holzapfel-Gasser-Ogden models that span from first-order to higher order and from isotropic to anisotropic materials, are served as examples. These detailed derivations are validated with numerical experiments that demonstrate excellent agreements with analytical and other computational solutions. Following this framework, one could implement with ease any hyperelastic model as user-defined functions in software packages or develop as an original source code from scratch.

Fully-coupled aeroelastic simulation with fluid compressibility - For application to vocal fold vibration.

In this study, a fully-coupled fluid-structure interaction model is developed for studying dynamic interactions between compressible fluid and aeroelastic structures. The technique is built based on the modified Immersed Finite Element Method (mIFEM), a robust numerical technique to simulate fluid-structure interactions that has capabilities to simulate high Reynolds number flows and handles large density disparities between the fluid and the solid. For accurate assessment of this intricate dynamic process between compressible fluid, such as air and aeroelastic structures, we included in the model the fluid compressibility in an isentropic process and a solid contact model. The accuracy of the compressible fluid solver is verified by examining acoustic wave propagations in a closed and an open duct, respectively. The fully-coupled fluid-structure interaction model is then used to simulate and analyze vocal folds vibrations using compressible air interacting with vocal folds that are represented as layered viscoelastic structures. Using physiological geometric and parametric setup, we are able to obtain a self-sustained vocal fold vibration with a constant inflow pressure. Parametric studies are also performed to study the effects of lung pressure and vocal fold tissue stiffness in vocal folds vibrations. All the case studies produce expected airflow behavior and a sustained vibration, which provide verification and confidence in our future studies of realistic acoustical studies of the phonation process.

Cell and nanoparticle transport in tumour microvasculature: the role of size, shape and surface functionality of nanoparticles.

Through nanomedicine, game-changing methods are emerging to deliver drug molecules directly to diseased areas. One of the most promising of these is the targeted delivery of drugs and imaging agents via drug carrier-based platforms. Such drug delivery systems can now be synthesized from a wide range of different materials, made in a number of different shapes, and coated with an array of different organic molecules, including ligands. If optimized, these systems can enhance the efficacy and specificity of delivery compared with those of non-targeted systems. Emerging integrated multiscale experiments, models and simulations have opened the door for endless medical applications. Current bottlenecks in design of the drug-carrying particles are the lack of knowledge about the dispersion of these particles in the microvasculature and of their subsequent internalization by diseased cells (Bao et al. 2014 J. R. Soc. Interface 11, 20140301 (doi:10.1098/rsif.2014.0301)). We describe multiscale modelling techniques that study how drug carriers disperse within the microvasculature. The immersed molecular finite-element method is adopted to simulate whole blood including blood plasma, red blood cells and nanoparticles. With a novel dissipative particle dynamics method, the beginning stages of receptor-driven endocytosis of nanoparticles can be understood in detail. Using this multiscale modelling method, we elucidate how the size, shape and surface functionality of nanoparticles will affect their dispersion in the microvasculature and subsequent internalization by targeted cells.

Evaluation of aerodynamic characteristics of a coupled fluid-structure system using generalized Bernoulli's principle: An application to vocal folds vibration.

In this work we explore the aerodynamics flow characteristics of a coupled fluid-structure interaction system using a generalized Bernoulli equation derived directly from the Cauchy momentum equations. Unlike the conventional Bernoulli equation where incompressible, inviscid, and steady flow conditions are assumed, this generalized Bernoulli equation includes the contributions from compressibility, viscous, and unsteadiness, which could be essential in defining aerodynamic characteristics. The application of the derived Bernoulli's principle is on a fully-coupled fluid-structure interaction simulation of the vocal folds vibration. The coupled system is simulated using the immersed finite element method where compressible Navier-Stokes equations are used to describe the air and an elastic pliable structure to describe the vocal fold. The vibration of the vocal fold works to open and close the glottal flow. The aerodynamics flow characteristics are evaluated using the derived Bernoulli's principles for a vibration cycle in a carefully partitioned control volume based on the moving structure. The results agree very well to experimental observations, which validate the strategy and its use in other types of flow characteristics that involve coupled fluid-structure interactions.

Modeling of Soft Tissues Interacting with Fluid (Blood or Air) Using the Immersed Finite Element Method.

This paper presents some biomedical applications that involve fluid-structure interactions which are simulated using the Immersed Finite Element Method (IFEM). Here, we first review the original and enhanced IFEM methods that are suitable to model incompressible or compressible fluid that can have densities that are significantly lower than the solid, such as air. Then, three biomedical applications are studied using the IFEM. Each of the applications may require a specific set of IFEM formulation for its respective numerical stability and accuracy due to the disparities between the fluid and the solid. We show that these biomedical applications require a fully-coupled and stable numerical technique in order to produce meaningful results.

Modified Immersed Finite Element Method For Fully-Coupled Fluid-Structure Interations.

In this paper, we develop a "modified" immersed finite element method (mIFEM), a non-boundary-fitted numerical technique, to study fluid-structure interactions. Using this method, we can more precisely capture the solid dynamics by solving the solid governing equation instead of imposing it based on the fluid velocity field as in the original immersed finite element (IFEM). Using the IFEM may lead to severe solid mesh distortion because the solid deformation is been over-estimated, especially for high Reynolds number flows. In the mIFEM, the solid dynamics is solved using appropriate boundary conditions generated from the surrounding fluid, therefore produces more accurate and realistic coupled solutions. We show several 2-D and 3-D testing cases where the mIFEM has a noticeable advantage in handling complicated fluid-structure interactions when the solid behavior dominates the fluid flow.

Toward generating low-friction nanoengineered surfaces with liquid-vapor interfaces.

Using molecular dynamics (MD), we investigate the importance of liquid-vapor interface topography in designing low-friction nanoengineered superhydrophobic surfaces. Shear flow is simulated on patterned surfaces. The relationship between the effective slip length and bubble meniscus curvature is attained by generating entrapped bubbles with large protrusion angles on patterned surfaces with nanoholes. We show that protruding bubbles can induce significant friction, which hinders the slip characteristics produced on liquid-vapor interfaces. By comparing surfaces with nanoholes and nanopillars, we also demonstrate that the continuity of the liquid-vapor interface can greatly influence slip. Our MD results yield an asymptotic behavior of slip length with varying gas fractions, which are found to be consistent with observations from simulations and analytical models produced in continuum studies.

Thermostats and thermostat strategies for molecular dynamics simulations of nanofluidics.

The thermostats in molecular dynamics (MD) simulations of highly confined channel flow may have significant influences on the fidelity of transport phenomena. In this study, we exploit non-equilibrium MD simulations to generate Couette flows with different combinations of thermostat algorithms and strategies. We provide a comprehensive analysis on the effectiveness of three thermostat algorithms Nosé-Hoover chain (NHC), Langevin (LGV) and dissipative particle dynamics (DPD) when applied in three thermostat strategies, thermostating either walls (TW) or fluid (TF), and thermostating both the wall and fluid (TWTF). Our results of thermal and mechanical properties show that the TW strategy more closely resembles experimental conditions. The TF and TWTF systems also produce considerably similar behaviors in weakly sheared systems, but deviate the dynamics in strongly sheared systems due to the isothermal condition. The LGV and DPD thermostats used in the TF and TWTF systems provide vital ways to yield correct dynamics in coarse-grained systems by tuning the fluid transport coefficients. Using conventional NHC thermostat to thermostat fluid only produces correct thermal behaviors in weakly sheared systems, and breaks down due to significant thermal inhomogeneity in strongly sheared systems.

Nanoscale simple-fluid behavior under steady shear.

In this study, we use two nonequilibrium molecular dynamics algorithms, boundary-driven shear and homogeneous shear, to explore the rheology and flow properties of a simple fluid undergoing steady simple shear. The two distinct algorithms are designed to elucidate the influences of nanoscale confinement. The results of rheological material functions, i.e., viscosity and normal pressure differences, show consistent Newtonian behaviors at low shear rates from both systems. The comparison validates that confinements of the order of 10 nm are not strong enough to deviate the simple fluid behaviors from the continuum hydrodynamics. The non-Newtonian phenomena of the simple fluid are further investigated by the homogeneous shear simulations with much higher shear rates. We observe the "string phase" at high shear rates by applying both profile-biased and profile-unbiased thermostats. Contrary to other findings where the string phase is found to be an artifact of the thermostats, we perform a thorough analysis of the fluid microstructures formed due to shear, which shows that it is possible to have a string phase and second shear thinning for dense simple fluids.

Investigating liquid-solid interfacial phenomena in a Couette flow at nanoscale.

This study investigates shear-induced liquid structure changes in nanoscale Couette flows and their corresponding flow boundary conditions. Molecular dynamics simulations are used to model a liquid argon slab confined between two smooth rigid copper walls with an applied velocity at the upper wall to generate a planar Couette flow. Depending on the applied wall velocity, different liquid structures or the orderings of the liquid at liquid-solid interfaces are identified when reaching steady states. We define three regimes based on the ordering of the liquid structure: Newtonian, layer, and oversheared. Each regime is characterized by the spatial probability distribution and structure factor. These liquid structures are strongly correlated with the liquid velocity and density profiles in the flow. Ultimately, the liquid structures also determine the boundary conditions from pure slip to multilayer locking at liquid-solid interfaces. Our results show that temperature and liquid-solid interaction parameter are also important factors in influencing the liquid structures formed near interfaces.

Nanoscale wetting on groove-patterned surfaces.

In this paper, nanoscale wetting on groove-patterned surfaces is thoroughly studied using molecular dynamics simulations. The results are compared with Wenzel's and Cassie's predictions to determine whether these continuum theories are still valid at the nanoscale for both hydrophobic and hydrophilic types of surfaces when the droplet size is comparable to the groove size. A system with a liquid mercury droplet and grooved copper substrate is simulated. The wetting properties are determined by measuring contact angles of the liquid droplet at equilibrium states. Correlations are established between the contact angle, roughness factor r, and surface fraction f. The results show that, for hydrophobic surfaces, the contact angle as a function of roughness factor and surface fraction on nanogrooved surfaces obeys the predictions from Wenzel's theory for wetted contacts and Cassie's theory for composite contacts. However, slight deviations occur in composite contacts when a small amount of liquid penetration is observed. The contact angle of this partial wetting cannot be accurately predicted using either Cassie's or Wenzel's theories. For hydrophilic surfaces, only wetted contacts are observed. In most cases, the resulting contact angles are found to be higher than Wenzel's predictions. At the nanoscale, high surface edge density plays an important role, which results in contact line pinning near plateau edges. For both hydrophobic and hydrophilic surfaces, substantial amount of anistropic spreading is found in the direction that is parallel to the grooves, especially at wetted or partially wetted contacts.

Characterizing left atrial appendage functions in sinus rhythm and atrial fibrillation using computational models.

Clinical studies show that the left atrial appendage, a blind-ended structure that is attached to the left atrium, may be the cause of 90% of atrial thrombi in atrial fibrillation (abnormal heart rhythm), and it is much reduced in sinus (normal) rhythm. In this paper, the effects of blood flows in left atrium and left atrial appendage are studied to help characterize the atrial appendage functions in sinus rhythm and atrial fibrillation using mathematical models. Our results show that the left atrial appendage is not functional in sinus rhythm because the atrial transmitral velocities remained almost identical for atria with and without appendage, which agrees with the current clinical observations. However, in atrial fibrillation, a proper atrial contraction is absent, which causes the second emptying velocity (A-wave) to be missing in both transmitral velocity and appendage filling/emptying velocity. Without the proper emptying of the blood, vortices generated in the chamber remain high strengths and with longer durations. They induce ineffective emptying of the blood in the atrium and appendage, which then lead to blood stagnation and subsequent thrombus formation.

Temperature control algorithms in dual control volume grand canonical molecular dynamics simulations of hydrogen diffusion in palladium.

The effectiveness of five temperature control algorithms for dual control volume grand canonical molecular dynamics is investigated in the study of hydrogen atom diffusion in a palladium bulk. The five algorithms, namely, Gaussian, generalized Gaussian moment thermostat (GGMT), velocity scaling, Nosé-Hoover (NH), and its enhanced version Nosé-Hoover chain (NHC) are examined in both equilibrium and nonequilibrium simulation studies. Our numerical results show that Gaussian yields the most inaccurate solutions for the hydrogen-palladium system due to the high friction coefficient generated from the large velocity fluctuation of hydrogen, while NHC, NH, and GGMT produce the most accurate temperature and density profiles in both equilibrium and nonequilibrium cases with their feedback control mechanisms. However, this feedback control also overestimates the self-diffusion coefficients in equilibrium systems and the diffusion coefficient in nonequilibrium systems. Velocity scaling thermostat produces slight inhomogeneities in the temperature and density profiles, but due to the dissipated heat accumulated in the control volumes it still yields accurate self-diffusion coefficients that are in good agreement with the experimental data at a wide range of temperatures while others tend to deviate.