Computational modeling of blood clot lysis considering the effect of vessel wall and pulsatile blood flow.

Stroke is one of the major causes of global death, which can occur due to blockage in a blood vessel by a clot. The immediate dissolving of the clot is essential to restore the blood flow and prevent tissue necrosis. Clot dissolution can be achieved via thrombolytic therapy using plasminogen activators. In this study, a clot dissolution model is developed for a three-dimensional patient-specific carotid artery that investigates the effect of different vessel wall models on clot dissolution. The lysis pattern of the clot and hemodynamics of blood flow are evaluated using three different models of the vessel wall, namely, rigid, linear elastic, and Mooney-Rivlin hyperelastic. The effect of flow condition is considered by solving the Navier-Stokes equations for the free flow domain and the Brinkman equation for the clot domain with the same pressure and velocity fields. This will result in continuous pressure and velocity over the interfaces of the free flow and clot domains. The blood inflow is assumed to be pulsatile. In addition, the species transport driven by diffusion and convection is considered to be different in the porous medium and plasma. The obtained results show that in all models, the starting time of clot volume decrease is almost the same and the clot starts dissolving from the inner curvature of the artery. However, in the hyperelastic model, dissolving the clot takes longer compared to the other two models. By monitoring the vessel wall deformation, the exact time of vessel recanalization is determined.

Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors.

Central Nervous System (CNS) malignant tumors are a leading cause of death worldwide with a high mortality rate. While numerous strategies have been proposed to treat CNS tumors, the treatment efficacy is still low mainly due to the existence of the Blood-Brain Barrier (BBB). BBB is a natural cellular layer between the circulatory system and brain extracellular fluid, limiting the transfer of drug particles and confining the routine treatment strategies in which drugs are released in the blood. Consequently, direct drug delivery methods have been devised to bypass the BBB. However, the efficiency of these methods is not enough to treat deep and large brain tumors. In the study at hand, the effect of focused ultrasound (FUS) waves on enhancing drug delivery to brain tumors, through ultrasound-assisted convection-enhanced delivery (UCED), has been investigated. First, brain mimicking gels were synthesized to mimic the CNS microenvironment, and the drug solution was injected into them. Second, FUS waves with the resonance frequency of 1.1 MHz were applied to the drug injected zone. Next, a finite element (FE) model was developed to evaluate the pre-existing equation in the literature for describing the drug delivery via acoustic streaming in brain tissue. Experimental results showed that the FUS transducer was able to enhance the drug volume distribution up to 500% relative to convection-enhanced delivery alone (CED). Numerical analysis showed that the FE model could replicate the experimental penetration depths with a mean difference value of less than 21%, and acoustic streaming plays a significant role in UCED. Therefore, the results of this study could open a new way to develop FE models of the brain to better evaluate the UCED and reduce the costs of conducting clinical and animal studies.

Time-domain ultrasound as prior information for frequency-domain compressive ultrasound for intravascular cell detection: A 2-cell numerical model.

This study proposes a new method for the detection of a weak scatterer among strong scatterers using prior-information ultrasound (US) imaging. A perfect application of this approach is in vivo cell detection in the bloodstream, where red blood cells (RBCs) serve as identifiable strong scatterers. In vivo cell detection can help diagnose cancer at its earliest stages, increasing the chances of survival for patients. This work combines time-domain US with frequency-domain compressive US imaging to detect a 20-µ MCF-7 circulating tumor cell (CTC) among a number of RBCs within a simulated venule inside the mouth. The 2D image reconstructed from the time-domain US is employed to simulate the reflected and scattered pressure field from the RBCs, which is then measured at the location of the receivers. The RBCs are tagged one time by a human operator and another time, automatically, by template-based computer vision. Next, the resulting signal from the RBCs is subtracted from the measured total signal in frequency domain to generate the scattered-field data, coming from the CTC alone. Feeding that signal and the background pressure field into a norm-one-based compressive sensing code enables detecting the CTC at various locations. As errors could arise in determining the location of the RBCs and their acoustic properties in the real world, small errors (up to 10% in the former and 5% in the latter) are purposefully introduced to the model, to which the proposed method is shown to be resilient. Localization errors are smaller than 12 µ when a human tags the RBCs and smaller than 25 µ when computer vision is applied. Despite its limitations, this study, for the first time, reports the results of combining two US modalities aimed at cell detection and introduces a unique and useful application for ultrahigh-frequency US imaging. It should be noted that this method can be used in detecting weak scatterers with ultrasound waves in other applications as well.

Effect of axonal fiber architecture on mechanical heterogeneity of the white matter-a statistical micromechanical model.

A diffusion tensor imaging (DTI) -based statistical micromechanical model was developed to study the effect of axonal fiber architecture on the inter- and intra-regional mechanical heterogeneity of the white matter. Three characteristic regions within the white matter, i.e., corpus callosum, brain stem, and corona radiata, were studied considering the previous observations of locations of diffuse axonal injury. The embedded element technique was used to create a fiber-reinforced model, where the fiber was characterized by a Holzapfel hyperelastic material model with variable dispersion of axonal orientations. A relationship between the fractional anisotropy and the dispersion parameter of the hyperelastic model was used to introduce the statistical DTI data into the representative volume element. The FA-informed statistical micromechanical models of three characteristic regions of white matter were developed by deriving the corresponding probabilistic measures of FA variations. Comparison of the model predictions and experimental data indicated a good agreement, suggesting that the model could reasonably capture the inter-regional heterogeneity of white matter. Moreover, the standard deviations of experimental results correlated well with the model predictions, suggesting that the model could capture the intra-regional mechanical heterogeneity for different regions of white matter.

Interaction analysis of a pregnant female uterus and fetus in a vehicle passing a speed bump.

Pregnant vehicle occupants experience relatively large acceleration when the vehicle passes a speed-bump. In this paper, the effect of such sudden acceleration on a pregnant uterus is investigated. A biomechanical model representing the fundamental dynamic behaviors of a pregnant uterus has been developed. The model relates to the 32nd week of gestation when the fetus is in head-down, occipito-anterior position. Considering the drag and squeeze effects of the amniotic fluid, we derive a comprehensive differential equation that represents the interaction of the uterus and fetus. Solving the governing equation, we obtain the system response to different speed-bump excitations. Using the fetal head injury criterion (HIC = 390), we evaluate the model response. Three risk zones (Low, Medium, and High) are introduced, and the effects of excitation characteristics on HIC are investigated. HIC enhances, sub-exponentially, as the excitation amplitude (width) increases (decreases). Three risk-bounds, corresponding to 25%, 75%, and 100% risk of injury, are developed in the "width-amplitude" and the "frequency-amplitude" planes. Considering a typical speed-bump of width and excitation amplitude of 0.5 m and 0.12 m, respectively, the driver should not hit the speed-bump at 42 km/h or more. We advise hitting such speed-bumps under 25 km/h, based on this paper's findings. According to the risk-bounds, the injury risk of an arbitrary speed-bump excitation, at any desired vehicle speed, can be determined. The findings can help to understand how a pregnant uterus and fetus are subjected to risk caused by a vehicle passing a speed-bump and to expand our knowledge to improve safety during pregnancy.

A Three-Dimensional Statistical Volume Element for Histology Informed Micromechanical Modeling of Brain White Matter.

This study presents a novel statistical volume element (SVE) for micromechanical modeling of the white matter structures, with histology-informed randomized distribution of axonal tracts within the extracellular matrix. The model was constructed based on the probability distribution functions obtained from the results of diffusion tensor imaging as well as the histological observations of scanning electron micrograph, at two structures of white matter susceptible to traumatic brain injury, i.e. corpus callosum and corona radiata. A simplistic representative volume element (RVE) with symmetrical arrangement of fully alligned axonal fibers was also created as a reference for comparison. A parametric study was conducted to find the optimum grid and edge size which ensured the periodicity and ergodicity of the SVE and RVE models. A multi-objective evolutionary optimization procedure was used to find the hyperelastic and viscoelastic material constants of the constituents, based on the experimentally reported responses of corpus callosum to axonal and transverse loadings. The optimal material properties were then used to predict the homogenized and localized responses of corpus callosum and corona radiata. The results indicated similar homogenized responses of the SVE and RVE under quasi-static extension, which were in good agreement with the experimental data. Under shear strain, however, the models exhibited different behaviors, with the SVE model showing much closer response to the experimental observations. Moreover, the SVE model displayed a significantly better agreement with the reports of the experiments at high strain rates. The results suggest that the randomized fiber architecture has a great influence on the validity of the micromechanical models of white matter, with a distinguished impact on the model's response to shear deformation and high strain rates. Moreover, it can provide a more detailed presentation of the localized responses of the tissue substructures, including the stress concentrations around the low caliber axonal tracts, which is critical for studying the axonal injury mechanisms.

Rigid-bar loading on pregnant uterus and development of pregnant abdominal response corridor based on finite element biomechanical model.

During pregnancy, traumas can threaten maternal and fetal health. Various trauma effects on a pregnant uterus are little investigated. In the present study, a finite element model of a uterus along with a fetus, placenta, amniotic fluid, and two most effective ligament sets is developed. This model allows numerical evaluation of various loading on a pregnant uterus. The model geometry is developed based on CT-scan data and validated using anthropometric data. Applying Ogden hyper-elastic theory, material properties of uterine wall and placenta are developed. After simulating the "rigid-bar" abdominal loading, the impact force and abdominal penetration are investigated. Findings are compared with the experimental abdominal response corridor, previously developed for a nonpregnant abdomen. "Response corridor" denotes a bounded envelope in response space, within which the system responses usually lie. Results show that at low abdominal penetrations (less than 45 mm), the pregnant abdomen response is highly compatible with the nonpregnant case. While, at large penetrations, the pregnant abdomen demonstrates stiffer behavior. The reason must be the existence of a fetus in the model. This reveals that the existing response corridors would not be reliable to be extended for a pregnant abdomen. Hence, response corridor development for a pregnant abdomen is a crucial task. In this study, a new fixed-back rigid-bar loading response corridor is proposed for a pregnant abdomen using the load-penetration behavior of the developed model. This model and response corridor can help to study the pregnant uterus response to environmental loading and investigate the injury risk to the uterus and fetus.

On the mechanical characteristics of graphene nanosheets: a fully nonlinear modified Morse model.

In this paper, the mechanical properties of graphene nanosheets are evaluated based on the nonlinear modified Morse model. The interatomic interactions including stretching and bending of the covalent bonds between carbon atoms, are replaced by nonlinear extensional and torsional spring-like elements. The finite element method is implemented to analyze the model under different loading conditions and linear characteristics of the graphene structure including the Young's modulus, surface modulus, shear modulus and Poisson's ratio are evaluated for various geometries and chirality where these properties are shown to be size and aspect ratio dependent. It is also found that when the dimensions of the sheets are greater than a certain threshold, the structure behaves quasi-isotropically and the directional elastic moduli become close to each other by a relative difference no more than 1%. Using the nonlinear stress-strain curve, the yielding point and ultimate stress and strains of the graphene sheet are also evaluated. The results of this study are compared with available experimental data and previous numerical simulations, where good agreement is achieved.

Numerical and Experimental Evaluation of High-Intensity Focused Ultrasound-Induced Lesions in Liver Tissue Ex Vivo.

OBJECTIVES: Recent advances in the field of acoustics and piezoelectric and ultrasound transducers have led to new approaches to the diagnosis and treatment of certain diseases. One method of treatment with ultrasonic waves is high-intensity focused ultrasound (HIFU) treatment, which is a thermal therapeutic method used to treat malignant tumors. Although a variety of treatment-planning strategies using ultrasonic waves have been investigated, little clinical success has been achieved. Computational modeling is a powerful tool for predicting device performance. METHODS: The heating induced by a concave transducer with operating powers of 85 and 135 W was studied, and the experimental results presented in this article verify its applicability. Numerical simulations of the nonlinear acoustic field were performed by using the Westervelt and Khokhlov-Zabolotskaya-Kuznetsov equations. Heat transfer was measured for the 2 operational powers, and the results were compared with ex vivo experimental results. In addition, thermal dose contours for both the simulation and experimental results were calculated to investigate the ablated area. RESULTS: Good agreement was found between the experimental and numerical results. The results show that the average temperature deviations calculated at the focal point were 12.8% and 4.3% for transducer powers of 85 and 135 W, respectively. CONCLUSIONS: This study provides guidance to HIFU practitioners in determining lesion size and identifying nonlinear effects that should be considered in HIFU procedures.

Simulation of Paramecium Chemotaxis Exposed to Calcium Gradients.

Paramecium or other ciliates have the potential to be utilized for minimally invasive surgery systems, making internal body organs accessible. Paramecium shows interesting responses to changes in the concentration of specific ions such as K(+), Mg(2+), and Ca(2+) in the ambient fluid. Some specific responses are observed as, changes in beat pattern of cilia and swimming toward or apart from the ion source. Therefore developing a model for chemotactic motility of small organisms is necessary in order to control the directional movements of these microorganisms before testing them. In this article, we have developed a numerical model, investigating the effects of Ca(2+) on swimming trajectory of Paramecium. Results for Ca(2+)-dependent chemotactic motility show that calcium gradients are efficient actuators for controlling the Paramecium swimming trajectory. After applying a very low Ca(2+) gradient, a directional chemotaxis of swimming Paramecium is observable in this model. As a result, chemotaxis is shown to be an efficient method for controlling the propulsion of these small organisms.

Size-dependent characteristics of electrostatically actuated fluid-conveying carbon nanotubes based on modified couple stress theory.

The paper presents the effects of fluid flow on the static and dynamic properties of carbon nanotubes that convey a viscous fluid. The mathematical model is based on the modified couple stress theory. The effects of various fluid parameters and boundary conditions on the pull-in voltages are investigated in detail. The applicability of the proposed system as nanovalves or nanosensors in nanoscale fluidic systems is elaborated. The results confirm that the nanoscale system studied in this paper can be properly applied for these purposes.