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Showing papers in "Annals of Biomedical Engineering in 2011"


Journal ArticleDOI
TL;DR: The objective of this article is to introduce a new equation that can be used to evaluate helmet performance by integrating player head impact exposure and risk of concussion by integrating the Summation of Tests for the Analysis of Risk (STAR) equation.
Abstract: In contrast to the publicly available data on the safety of automobiles, consumers have no analytical mechanism to evaluate the protective performance of football helmets. The objective of this article is to fill this void by introducing a new equation that can be used to evaluate helmet performance by integrating player head impact exposure and risk of concussion. The Summation of Tests for the Analysis of Risk (STAR) equation relates on-field impact exposure to a series of 24 drop tests performed at four impact locations and six impact energy levels. Using 62,974 head acceleration data points collected from football players, the number of impacts experienced for one full season was translated to 24 drop test configurations. A new injury risk function was developed from 32 measured concussions and associated exposure data to assess risk of concussion for each impact. Finally, the data from all 24 drop tests is combined into one number using the STAR formula that incorporates the predicted exposure and injury risk for one player for one full season of practices and games. The new STAR evaluation equation will provide consumers with a meaningful metric to assess the relative performance of football helmets.

266 citations


Journal ArticleDOI
TL;DR: Silicon photomultipliers clearly have the potential to be the photodetector of choice for some, or even perhaps most, PET systems, and therefore an investigation into optimal design and operating conditions is underway together with detailed characterization of SiPM-based PET detectors.
Abstract: Historically, positron emission tomography (PET) systems have been based on scintillation crystals coupled to photomultipliers tubes (PMTs). However, the limited quantum efficiency, bulkiness, and relatively high cost per unit surface area of PMTs, along with the growth of new applications for PET, offers opportunities for other photodetectors. Among these, small-animal scanners, hybrid PET/MRI systems, and incorporation of time-of-flight information are of particular interest and require low-cost, compact, fast, and magnetic field compatible photodetectors. With high quantum efficiency and compact structure, avalanche photodiodes (APDs) overcome several of the drawbacks of PMTs, but this is offset by degraded signal-to-noise and timing properties. Silicon photomultipliers (SiPMs) offer an alternative solution, combining many of the advantages of PMTs and APDs. They have high gain, excellent timing properties and are insensitive to magnetic fields. At the present time, SiPM technology is rapidly developing and therefore an investigation into optimal design and operating conditions is underway together with detailed characterization of SiPM-based PET detectors. Published data are extremely promising and show good energy and timing resolution, as well as the ability to decode small scintillator arrays. SiPMs clearly have the potential to be the photodetector of choice for some, or even perhaps most, PET systems.

238 citations


Journal ArticleDOI
TL;DR: Despite the importance of user preferences, they are rarely considered and as such there is a lack of high-quality studies in this area, and the aim of this systematic review was to determine both patients’ and clinicians’ preferences for non-invasive body-worn sensor systems.
Abstract: User preferences need to be taken into account in order to be able to design devices that will gain acceptance both in a clinical and home setting. Sensor systems become redundant if patients or clinicians do not want to work with them. The aim of this systematic review was to determine both patients’ and clinicians’ preferences for non-invasive body-worn sensor systems. A search for relevant articles and conference proceedings was performed using MEDLINE, EMBASE, Current Contents Connect, and EEEI explore. In total 843 papers were identified of which only 11 studies were deemed suitable for inclusion. A range of different clinically relevant user groups were included. The key user preferences were that a body-worn sensor system should be compact, embedded and simple to operate and maintain. It also should not affect daily behavior nor seek to directly replace a health care professional. It became apparent that despite the importance of user preferences, they are rarely considered and as such there is a lack of high-quality studies in this area. We therefore would like to encourage researchers to focus on the implications of user preferences when designing wearable sensor systems.

215 citations


Journal ArticleDOI
TL;DR: This review provides the first comprehensive overview of the underlying mechanisms that modulate SMC secretion, alignment, contraction, proliferation, apoptosis, differentiation, and migration in response to 2-dimensional laminar, pulsatile, and oscillating flow shear stresses and 3D interstitial flow.
Abstract: Understanding how vascular wall endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) sense and transduce the stimuli of hemodynamic forces (shear stress, cyclic strain, and hydrostatic pressure) into intracellular biochemical signals is critical to prevent vascular disease development and progression. ECs lining the vessel lumen directly sense alterations in blood flow shear stress and then communicate with medial SMCs and adventitial FBs to regulate vessel function and disease. Shear stress mechanotransduction in ECs has been extensively studied and reviewed. In the case of endothelial damage, blood flow shear stress may directly act on the superficial layer of SMCs and transmural interstitial flow may be elevated on medial SMCs and adventitial FBs. Therefore, it is also important to investigate direct shear effects on vascular SMCs as well as FBs. The work published in the last two decades has shown that shear stress and interstitial flow have significant influences on vascular SMCs and FBs. This review summarizes work that considered direct shear effects on SMCs and FBs and provides the first comprehensive overview of the underlying mechanisms that modulate SMC secretion, alignment, contraction, proliferation, apoptosis, differentiation, and migration in response to 2-dimensional (2D) laminar, pulsatile, and oscillating flow shear stresses and 3D interstitial flow. A mechanistic model of flow sensing by SMCs is also provided to elucidate possible mechanotransduction pathways through surface glycocalyx, integrins, membrane receptors, ion channels, and primary cilia. Understanding flow-mediated mechanotransduction in SMCs and FBs and the interplay with ECs should be helpful in exploring strategies to prevent flow-initiated atherosclerosis and neointima formation and has implications in vascular tissue engineering.

214 citations


Journal ArticleDOI
TL;DR: Two sets of cadaveric femora with bone densities varying from normal to osteoporotic were used to build, refine, and validate a new class of QCT/FEA models for hip fracture under loading conditions that simulate a sideways fall on the hip.
Abstract: Clinical implementation of quantitative computed tomography-based finite element analysis (QCT/FEA) of proximal femur stiffness and strength to assess the likelihood of proximal femur (hip) fractures requires a unified modeling procedure, consistency in predicting bone mechanical properties, and validation with realistic test data that represent typical hip fractures, specifically, a sideways fall on the hip. We, therefore, used two sets (n = 9, each) of cadaveric femora with bone densities varying from normal to osteoporotic to build, refine, and validate a new class of QCT/FEA models for hip fracture under loading conditions that simulate a sideways fall on the hip. Convergence requirements of finite element models of the first set of femora led to the creation of a new meshing strategy and a robust process to model proximal femur geometry and material properties from QCT images. We used a second set of femora to cross-validate the model parameters derived from the first set. Refined models were validated experimentally by fracturing femora using specially designed fixtures, load cells, and high speed video capture. CT image reconstructions of fractured femora were created to classify the fractures. The predicted stiffness (cross-validation R2 = 0.87), fracture load (cross-validation R2 = 0.85), and fracture patterns (83% agreement) correlated well with experimental data.

211 citations


Journal ArticleDOI
TL;DR: The current research and development status of surface modification technologies of Mg alloys for biomedical materials research is given and the advantages/disadvantages of the different methods and with regard to the most promising method are discussed.
Abstract: In recent years, research on magnesium (Mg) alloys had increased significantly for hard tissue replacement and stent application due to their outstanding advantages. Firstly, Mg alloys have mechanical properties similar to bone which avoid stress shielding. Secondly, they are biocompatible essential to the human metabolism as a factor for many enzymes. In addition, main degradation product Mg is an essential trace element for human enzymes. The most important reason is they are perfectly biodegradable in the body fluid. However, extremely high degradation rate, resulting in too rapid loss of mechanical strength in chloride containing environments limits their applications. Engineered artificial biomaterials with appropriate mechanical properties, surface chemistry, and surface topography are in a great demand. As the interaction between the cells and tissues with biomaterials at the tissue–implant interface is a surface phenomenon; surface properties play a major role in determining both the biological response to implants and the material response to the physiological condition. Therefore, the ability to modify the surface properties while preserve the bulk properties is important, and surface modification to form a hard, biocompatible and corrosion resistant modified layer have always been an interesting topic in biomaterials field. In this article, attempts are made to give an overview of the current research and development status of surface modification technologies of Mg alloys for biomedical materials research. Further, the advantages/disadvantages of the different methods and with regard to the most promising method for Mg alloys are discussed. Finally, the scientific challenges are proposed based on own research and the work of other scientists.

167 citations


Journal ArticleDOI
TL;DR: This review highlights what the authors currently know about the biomechanical forces generated in the tumor microenvironment, how they arise, and how these forces can dramatically influence cell behavior, drawing not only upon studies directly related to cancer and tumor cells, but also work in other fields that have shown the effects of these types of mechanical forces vis-à-vis cell behaviors relevant to the tumormicroenvironment.
Abstract: The importance of the tumor microenvironment in cancer progression is indisputable, yet a key component of the microenvironment—biomechanical forces—remains poorly understood. Tumor growth and progression is paralleled by a host of physical changes in the tumor microenvironment, such as growth-induced solid stresses, increased matrix stiffness, high fluid pressure, and increased interstitial flow. These changes to the biomechanical microenvironment promote tumorigenesis and tumor cell invasion and induce stromal cells—such as fibroblasts, immune cells, and endothelial cells—to change behavior and support cancer progression. This review highlights what we currently know about the biomechanical forces generated in the tumor microenvironment, how they arise, and how these forces can dramatically influence cell behavior, drawing not only upon studies directly related to cancer and tumor cells, but also work in other fields that have shown the effects of these types of mechanical forces vis-a-vis cell behaviors relevant to the tumor microenvironment. By understanding how all of these biomechanical forces can affect tumor cells, stromal cells, and tumor–stromal crosstalk, as well as alter how tumor and stromal cells perceive other extracellular signals in the tumor microenvironment, we can develop new approaches for diagnosis, prognosis, and ultimately treatment of cancer.

161 citations


Journal ArticleDOI
TL;DR: Non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma may provide a novel approach to treat malignancies via induction of apoptosis through a pathway that appears to be dependent on production of intracellular ROS.
Abstract: Non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma may provide a novel approach to treat malignancies via induction of apoptosis. The purpose of this study was to evaluate the potential of DBD plasma to induce apoptosis in melanoma cells. Melanoma cells were exposed to plasma at doses that did not induce necrosis, and cell viability and apoptotic activity were evaluated by Trypan blue exclusion test, Annexin-V/PI staining, caspase-3 cleavage, and TUNEL® analysis. Trypan blue staining revealed that non-thermal plasma treatment significantly decreased the viability of cells in a dose-dependent manner 3 and 24 h after plasma treatment. Annexin-V/PI staining revealed a significant increase in apoptosis in plasma-treated cells at 24, 48, and 72 h post-treatment (p < 0.001). Caspase-3 cleavage was observed 48 h post-plasma treatment at a dose of 15 J/cm(2). TUNEL® analysis of plasma-treated cells demonstrated an increase in apoptosis at 48 and 72 h post-treatment (p < 0.001) at a dose of 15 J/cm(2). Pre-treatment with N-acetyl-L: -cysteine (NAC), an intracellular reactive oxygen species (ROS) scavenger, significantly decreased apoptosis in plasma-treated cells at 5 and 15 J/cm(2). Plasma treatment induces apoptosis in melanoma cells through a pathway that appears to be dependent on production of intracellular ROS. DBD plasma production of intracellular ROS leads to dose-dependent DNA damage in melanoma cells, detected by γ-H2AX, which was completely abrogated by pre-treating cells with ROS scavenger, NAC. Plasma-induced DNA damage in turn may lead to the observed plasma-induced apoptosis. Since plasma is non-thermal, it may be used to selectively treat malignancies.

153 citations


Journal ArticleDOI
TL;DR: The geometry of a seated 50th percentile male serves as the foundation of a global effort to develop the next-generation computational human body model for injury prediction and prevention, and is intended for subsequent use in nonlinear dynamics solvers.
Abstract: The objective of this study was to develop full body CAD geometry of a seated 50th percentile male. Model development was based on medical image data acquired for this study, in conjunction with extensive data from the open literature. An individual (height, 174.9 cm, weight, 78.6 ± 0.77 kg, and age 26 years) was enrolled in the study for a period of 4 months. 72 scans across three imaging modalities (CT, MRI, and upright MRI) were collected. The whole-body dataset contains 15,622 images. Over 300 individual components representing human anatomy were generated through segmentation. While the enrolled individual served as a template, segmented data were verified against, or augmented with, data from over 75 literature sources on the average morphology of the human body. Non-Uniform Rational B-Spline (NURBS) surfaces with tangential (G1) continuity were constructed over all the segmented data. The sagittally symmetric model consists of 418 individual components representing bones, muscles, organs, blood vessels, ligaments, tendons, cartilaginous structures, and skin. Length, surface area, and volumes of components germane to crash injury prediction are presented. The total volume (75.7 × 103 cm(3)) and surface area (1.86 × 102 cm(2)) of the model closely agree with the literature data. The geometry is intended for subsequent use in nonlinear dynamics solvers, and serves as the foundation of a global effort to develop the next-generation computational human body model for injury prediction and prevention.

148 citations


Journal ArticleDOI
TL;DR: It is demonstrated that ECs discriminate between positive and negative WSSG under high WSS conditions, which may contribute to pathogenic remodeling that occurs at bifurcations preceding aneurysm formation.
Abstract: Cerebral aneurysms develop near bifurcation apices, where complex hemodynamics occur: Flow impinges on the apex, accelerates into branches, then slows again distally, creating high wall shear stress (WSS) and positive and negative spatial gradients in WSS (WSSG). Endothelial responses to these kinds of high WSS hemodynamic environments are not well characterized. We examined endothelial cells (ECs) under elevated WSS and positive and negative WSSG using a flow chamber with constant-height channels to create regions of uniform WSS and converging and diverging channels to create positive and negative WSSG, respectively. Cultured bovine aortic ECs were subjected to 3.5 and 28.4 Pa with and without WSSG for 24 and 36 h. High WSS inhibited EC alignment to flow, increased EC proliferation assessed by bromodeoxyuridine incorporation, and increased apoptosis determined by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling. These responses to high WSS were either accentuated or ameliorated by WSSG: Positive WSSG (+980 Pa/m) inhibited alignment and stimulated proliferation and apoptosis, whereas negative WSSG (−1120 Pa/m) promoted alignment and suppressed proliferation and apoptosis. These results demonstrate that ECs discriminate between positive and negative WSSG under high WSS conditions. EC responses to positive WSSG may contribute to pathogenic remodeling that occurs at bifurcations preceding aneurysm formation.

148 citations


Journal ArticleDOI
TL;DR: The 3D simulations with the rigid walls predict higher amplitude of the flowrate and pressure temporal oscillations than the one-dimensional simulations with compliant walls at various segments even for small time-variations in the arterial cross-sectional areas.
Abstract: We compare results from numerical simulations of pulsatile blood flow in two patient-specific intracranial arterial networks using one-dimensional (1D) and three-dimensional (3D) models. Specifically, we focus on the pressure and flowrate distribution at different segments of the network computed by the two models. Results obtained with 1D and 3D models with rigid walls show good agreement in massflow distribution at tens of arterial junctions and also in pressure drop along the arteries. The 3D simulations with the rigid walls predict higher amplitude of the flowrate and pressure temporal oscillations than the 1D simulations with compliant walls at various segments even for small time-variations in the arterial cross-sectional areas. Sensitivity of the flow and pressure with respect to variation in the elasticity parameters is investigated with the 1D model.

Journal ArticleDOI
TL;DR: Evidence is provided that skull flexure is a likely candidate for the development of ICP gradients within the rat brain and the bone plates between the lambda, bregma, and midline sutures are probable regions for the greatest flexure to occur.
Abstract: The manner in which energy from an explosion is transmitted into the brain is currently a highly debated topic within the blast injury community. This study was conducted to investigate the injury biomechanics causing blast-related neurotrauma in the rat. Biomechanical responses of the rat head under shock wave loading were measured using strain gauges on the skull surface and a fiber optic pressure sensor placed within the cortex. MicroCT imaging techniques were applied to quantify skull bone thickness. The strain gauge results indicated that the response of the rat skull is dependent on the intensity of the incident shock wave; greater intensity shock waves cause greater deflections of the skull. The intracranial pressure (ICP) sensors indicated that the peak pressure developed within the brain was greater than the peak side-on external pressure and correlated with surface strain. The bone plates between the lambda, bregma, and midline sutures are probable regions for the greatest flexure to occur. The data provides evidence that skull flexure is a likely candidate for the development of ICP gradients within the rat brain. This dependency of transmitted stress on particular skull dynamics for a given species should be considered by those investigating blast-related neurotrauma using animal models.

Journal ArticleDOI
TL;DR: It is hypothesized that aneurysm morphology and wall thickness are more predictive of rupture risk and can be the deciding factors in the clinical management of the disease.
Abstract: Recent studies have shown that the maximum transverse diameter of an abdominal aortic aneurysm (AAA) and expansion rate are not entirely reliable indicators of rupture potential. We hypothesize that aneurysm morphology and wall thickness are more predictive of rupture risk and can be the deciding factors in the clinical management of the disease. A non-invasive, image-based evaluation of AAA shape was implemented on a retrospective study of 10 ruptured and 66 unruptured aneurysms. Three-dimensional models were generated from segmented, contrast-enhanced computed tomography images. Geometric indices and regional variations in wall thickness were estimated based on novel segmentation algorithms. A model was created using a J48 decision tree algorithm and its performance was assessed using ten-fold cross validation. Feature selection was performed using the χ2-test. The model correctly classified 65 datasets and had an average prediction accuracy of 86.6% (κ = 0.37). The highest ranked features were sac length, sac height, volume, surface area, maximum diameter, bulge height, and intra-luminal thrombus volume. Given that individual AAAs have complex shapes with local changes in surface curvature and wall thickness, the assessment of AAA rupture risk should be based on the accurate quantification of aneurysmal sac shape and size.

Journal ArticleDOI
TL;DR: The results indicate that BMS cells aligned in the direction of PLLA fibers to form long cell extensions, and fiber orientation affected the extent of mineralization, but it had no effect on cell proliferation or mRNA expression of osteogenic markers.
Abstract: The fibrillar structure and sub-micron diameter of electrospun nanofibers can be used to reproduce the morphology and structure of the natural extracellular matrix (ECM). The objective of this work was to investigate the effect of fiber alignment on osteogenic differentiation of bone marrow stromal (BMS) cells. Random and aligned poly(l-lactide) (PLLA) nanofibers were produced by collecting the spun fibers on a stationary plate and a rotating wheel, respectively, as the ground electrode. Morphology and alignment of the BMS cells seeded on the fibers were characterized by SEM. The effect of fiber orientation on osteogenic differentiation of BMS cells was determined by measuring alkaline phosphatase (ALPase) activity, calcium content, and mRNA expression levels of osteogenic markers. There was a strong correlation between the fiber and cell distributions for the random (p = 0.16) and aligned (p = 0.81) fibers. Percent deviation from ideal randomness (PDIR) values indicated that cells seeded on the random fibers (PDIR = 6.5%) were likely to be distributed randomly in all directions while cells seeded on the aligned fibers (PDIR = 86%) were highly likely to be aligned with the direction of fibers. BMS cell seeded on random and aligned fibers had similar cell count and ALPase activity with incubation time, but the calcium content on aligned fibers was significantly higher after 21 days compared to that of random fibers (p = 0.003). Osteopontin (OP) and osteocalcin (OC) expression levels of BMS cells on fibers increased with incubation time. However, there was no difference between the expression levels of OP and OC on aligned vs. random fibers. The results indicate that BMS cells aligned in the direction of PLLA fibers to form long cell extensions, and fiber orientation affected the extent of mineralization, but it had no effect on cell proliferation or mRNA expression of osteogenic markers.

Journal ArticleDOI
TL;DR: Results predicted by the porous medium approach compare well with the real stent geometry model and allow predicting the main effects of the device on intra-aneurismal flow, facilitating thus the analysis.
Abstract: Intracranial aneurysms may be treated by flow diverters, alternatively to stents and coils combination. Numerical simulation allows the assessment of the complex nature of aneurismal flow. Endovascular devices present a rather dense and fine strut network, increasing the complexity of the meshing. We propose an alternative strategy, which is based on the modeling of the device as a porous medium. Two patient-specific aneurysm data sets were reconstructed using conventional clinical setups. The aneurysms selection was done so that intra-aneurismal flow was shear driven in one and inertia driven in the other. Stents and their porous medium analog were positioned at the aneurysm neck. Physiological flow and standard boundary conditions were applied. The comparison between both approaches was done by analyzing the velocity, vorticity, and shear rate magnitudes inside the aneurysm as well as the wall shear stress (WSS) at the aneurysm surface. Simulations without device were also computed. The average flow reduction reaches 76 and 41% for the shear and inertia driven flow models, respectively. When comparing the two approaches, results show a remarkable similarity in the flow patterns and magnitude. WSS, iso-velocity surfaces and velocity on a trans-sectional plane are in fairly good agreement. The root mean squared error on the investigated parameters reaches 20% for aneurysm velocity, 30.6% for aneurysm shear rate, and 47.4% for aneurysm vorticity. It reaches 20.6% for WSS computed on the aneurysm surface. The advantages of this approach reside in its facility to implement and in the gain in computational time. Results predicted by the porous medium approach compare well with the real stent geometry model and allow predicting the main effects of the device on intra-aneurismal flow, facilitating thus the analysis.

Journal ArticleDOI
TL;DR: The capabilities of numerical simulations incorporating deformable walls to capture both the vessel wall motion and wave propagation by accurately predicting the changes in the flow and pressure waveforms at various locations down the length of the deformable flow phantoms are demonstrated.
Abstract: The purpose of this article is to validate numerical simulations of flow and pressure incorporating deformable walls using in vitro flow phantoms under physiological flow and pressure conditions. We constructed two deformable flow phantoms mimicking a normal and a restricted thoracic aorta, and used a Windkessel model at the outlet boundary. We acquired flow and pressure data in the phantom while it operated under physiological conditions. Next, insilico numerical simulations were performed, and velocities, flows, and pressures in the in silico simulations were compared to those measured in the in vitro phantoms. The experimental measurements and simulated results of pressure and flow waveform shapes and magnitudes compared favorably at all of the different measurement locations in the two deformable phantoms. The average difference between measured and simulated flow and pressure was approximately 3.5 cc/s (13% of mean) and 1.5 mmHg (1.8% of mean), respectively. Velocity patterns also showed good qualitative agreement between experiment and simulation especially in regions with less complex flow patterns. We demonstrated the capabilities of numerical simulations incorporating deformable walls to capture both the vessel wall motion and wave propagation by accurately predicting the changes in the flow and pressure waveforms at various locations down the length of the deformable flow phantoms.

Journal ArticleDOI
TL;DR: A cross-sectional area threshold is identified below which the RBC membrane properties begin to dominate its flow behavior at room temperature; at physiological temperatures this effect is less profound.
Abstract: We investigate the biophysical characteristics of healthy human red blood cells (RBCs) traversing microfluidic channels with cross-sectional areas as small as 2.7 × 3 μm. We combine single RBC optical tweezers and flow experiments with corresponding simulations based on dissipative particle dynamics (DPD), and upon validation of the DPD model, predictive simulations and companion experiments are performed in order to quantify cell deformation and pressure–velocity relationships for different channel sizes and physiologically relevant temperatures. We discuss conditions associated with the shape transitions of RBCs along with the relative effects of membrane and cytosol viscosity, plasma environments, and geometry on flow through microfluidic systems at physiological temperatures. In particular, we identify a cross-sectional area threshold below which the RBC membrane properties begin to dominate its flow behavior at room temperature; at physiological temperatures this effect is less profound.

Journal ArticleDOI
TL;DR: The strong similarities observed for the three BCs models suggest that vessel and aneurysm geometry have the strongest influence on aneurYSmal hemodynamics, and a distributed circulation model may represent the best option when CFD is used for large cohort studies.
Abstract: Modeling of flow in intracranial aneurysms (IAs) requires flow information at the model boundaries. In absence of patient-specific measurements, typical or modeled boundary conditions (BCs) are often used. This study investigates the effects of modeled versus patient-specific BCs on modeled hemodynamics within IAs. Computational fluid dynamics (CFD) models of five IAs were reconstructed from three-dimensional rotational angiography (3DRA). BCs were applied using in turn patient-specific phase-contrast-MR (pc-MR) measurements, a 1D-circulation model, and a physiologically coherent method based on local WSS at inlets. The Navier–Stokes equations were solved using the Ansys®-CFX™ software. Wall shear stress (WSS), oscillatory shear index (OSI), and other hemodynamic indices were computed. Differences in the values obtained with the three methods were analyzed using boxplot diagrams. Qualitative similarities were observed in the flow fields obtained with the three approaches. The quantitative comparison showed smaller discrepancies between pc-MR and 1D-model data, than those observed between pc-MR and WSS-scaled data. Discrepancies were reduced when indices were normalized to mean hemodynamic aneurysmal data. The strong similarities observed for the three BCs models suggest that vessel and aneurysm geometry have the strongest influence on aneurysmal hemodynamics. In absence of patient-specific BCs, a distributed circulation model may represent the best option when CFD is used for large cohort studies.

Journal ArticleDOI
TL;DR: This study bridges the gap between low intensity volunteer impacts and high intensity cadaver impacts, and predicts tissue level response to assess the potential for occupant injury.
Abstract: Predicting neck kinematics and tissue level response is essential to evaluate the potential for occupant injury in rear impact. A detailed 50th percentile male finite element model, previously validated for frontal impact, was validated for rear impact scenarios with material properties based on actual tissue properties from the literature. The model was validated for kinematic response using 4g volunteer and 7g cadaver rear impacts, and at the tissue level with 8g isolated full spine rear impact data. The model was then used to predict capsular ligament (CL) strain for increasing rear impact severity, since CL strain has been implicated as a source of prolonged pain resulting from whiplash injury. The model predicted the onset of CL injury for a 14g rear impact, in agreement with motor vehicle crash epidemiology. More extensive and severe injuries were predicted with increasing impact severity. The importance of muscle activation was demonstrated for a 7g rear impact where the CL strain was reduced from 28 to 13% with active muscles. These aspects have not previously been demonstrated experimentally, since injurious load levels cannot be applied to live human subjects. This study bridges the gap between low intensity volunteer impacts and high intensity cadaver impacts, and predicts tissue level response to assess the potential for occupant injury.

Journal ArticleDOI
TL;DR: This study demonstrates that the proposed models can predict pressure–area dynamics and that model parameters can be extracted for further interpretation of biomechanical properties and indicates that optimal model selection depends on the artery type.
Abstract: A better understanding of the biomechanical properties of the arterial wall provides important insight into arterial vascular biology under normal (healthy) and pathological conditions. This insight has potential to improve tracking of disease progression and to aid in vascular graft design and implementation. In this study, we use linear and nonlinear viscoelastic models to predict biomechanical properties of the thoracic descending aorta and the carotid artery under ex vivo and in vivo conditions in ovine and human arteries. Models analyzed include a four-parameter (linear) Kelvin viscoelastic model and two five-parameter nonlinear viscoelastic models (an arctangent and a sigmoid model) that relate changes in arterial blood pressure to the vessel cross-sectional area (via estimation of vessel strain). These models were developed using the framework of Quasilinear Viscoelasticity (QLV) theory and were validated using measurements from the thoracic descending aorta and the carotid artery obtained from human and ovine arteries. In vivo measurements were obtained from 10 ovine aortas and 10 human carotid arteries. Ex vivo measurements (from both locations) were made in 11 male Merino sheep. Biomechanical properties were obtained through constrained estimation of model parameters. To further investigate the parameter estimates, we computed standard errors and confidence intervals and we used analysis of variance to compare results within and between groups. Overall, our results indicate that optimal model selection depends on the artery type. Results showed that for the thoracic descending aorta (under both experimental conditions), the best predictions were obtained with the nonlinear sigmoid model, while under healthy physiological pressure loading the carotid arteries nonlinear stiffening with increasing pressure is negligible, and consequently, the linear (Kelvin) viscoelastic model better describes the pressure–area dynamics in this vessel. Results comparing biomechanical properties show that the Kelvin and sigmoid models were able to predict the zero-pressure vessel radius; that under ex vivo conditions vessels are more rigid, and comparatively, that the carotid artery is stiffer than the thoracic descending aorta; and that the viscoelastic gain and relaxation parameters do not differ significantly between vessels or experimental conditions. In conclusion, our study demonstrates that the proposed models can predict pressure–area dynamics and that model parameters can be extracted for further interpretation of biomechanical properties.

Journal ArticleDOI
TL;DR: A biomechanical model to estimate anterior tibial translation (ATT), anterior shear forces, and ligament loading in the healthy and anterior cruciate ligament (ACL)-deficient knee joint during gait was developed.
Abstract: The purpose of this study was to develop a biomechanical model to estimate anterior tibial translation (ATT), anterior shear forces, and ligament loading in the healthy and anterior cruciate ligament (ACL)-deficient knee joint during gait. This model used electromyography (EMG), joint position, and force plate data as inputs to calculate ligament loading during stance phase. First, an EMG-driven model was used to calculate forces for the major muscles crossing the knee joint. The calculated muscle forces were used as inputs to a knee model that incorporated a knee–ligament model in order to solve for ATT and ligament forces. The model took advantage of using EMGs as inputs, and could account for the abnormal muscle activation patterns of ACL-deficient gait. We validated our model by comparing the calculated results with previous in vitro, in vivo, and numerical studies of healthy and ACL-deficient knees, and this gave us confidence on the accuracy of our model calculations. Our model predicted that ATT increased throughout stance phase for the ACL-deficient knee compared with the healthy knee. The medial collateral ligament functioned as the main passive restraint to anterior shear force in the ACL-deficient knee. Although strong co-contraction of knee flexors was found to help restrain ATT in the ACL-deficient knee, it did not counteract the effect of ACL rupture. Posterior inclination angle of the tibial plateau was found to be a crucial parameter in determining knee mechanics, and increasing the tibial slope inclination in our model would increase the resulting ATT and ligament forces in both healthy and ACL-deficient knees.

Journal ArticleDOI
TL;DR: Evaluating the delivery of inhaled pharmaceutical aerosols using an enhanced condensational growth (ECG) approach in an airway model extending from the oral cavity to the end of the tracheobronchial (TB) region indicated that targeting the region of TB deposition by controlling the inlet temperature conditions and initial aerosol size also appeared possible.
Abstract: The objective of this study was to evaluate the delivery of inhaled pharmaceutical aerosols using an enhanced condensational growth (ECG) approach in an airway model extending from the oral cavity to the end of the tracheobronchial (TB) region. The geometry consisted of an elliptical mouth-throat (MT) model, the upper TB airways extending to bifurcation B3, and a subsequent individual path model entering the right lower lobe of the lung. Submicrometer monodisperse aerosols with diameters of 560 and 900 nm were delivered to the mouth inlet under control (25 °C with subsaturated air) or ECG (39 or 42 °C with saturated air) conditions. Flow fields and droplet characteristics were simulated using a computational fluid dynamics model that was previously demonstrated to accurately predict aerosol size growth and deposition. Results indicated that both the control and ECG delivery cases produced very little deposition in the MT and upper TB model (approximately 1%). Under ECG delivery conditions, large size increases of the aerosol droplets were observed resulting in mass median aerodynamic diameters of 2.4–3.3 μm exiting B5. This increase in aerosol size produced an order of magnitude increase in aerosol deposition within the TB airways compared with the controls, with TB deposition efficiencies of approximately 32–46% for ECG conditions. Estimates of downstream pulmonary deposition indicted near full lung retention of the aerosol during ECG delivery. Furthermore, targeting the region of TB deposition by controlling the inlet temperature conditions and initial aerosol size also appeared possible.

Journal ArticleDOI
TL;DR: The mathematical model presented in this article is a prerequisite for developing a mechanistic understanding of the relationships among vasculature pulsations, CSF flow, and CSF pressure waves in the CNS.
Abstract: Cine-phase-contrast-MRI was used to measure the three-dimensional cerebrospinal fluid (CSF) flow field inside the central nervous system (CNS) of a healthy subject. Image reconstruction and grid generation tools were then used to develop a three-dimensional fluid–structure interaction model of the CSF flow inside the CNS. The CSF spaces were discretized using the finite-element method and the constitutive equations for fluid and solid motion solved in ADINA-FSI 8.6. Model predictions of CSF velocity magnitude and stroke volume were found to be in excellent agreement with the experimental data. CSF pressure gradients and amplitudes were computed in all regions of the CNS. The computed pressure gradients and amplitudes closely match values obtained clinically. The highest pressure amplitude of 77 Pa was predicted to occur in the lateral ventricles. The pressure gradient between the lateral ventricles and the lumbar region of the spinal canal did not exceed 132 Pa (~1 mmHg) at any time during the cardiac cycle. The pressure wave speed in the spinal canal was predicted and found to agree closely with values previously reported in the literature. Finally, the forward and backward motion of the CSF in the ventricles was visualized, revealing the complex mixing patterns in the CSF spaces. The mathematical model presented in this article is a prerequisite for developing a mechanistic understanding of the relationships among vasculature pulsations, CSF flow, and CSF pressure waves in the CNS.

Journal ArticleDOI
TL;DR: The results suggest that the combination of sampling rate of 500 Hz and high-pass cut-off frequency of 60 Hz should be an optimal selection in EMG recordings for recognition of different arm movements without sacrificing too much of classification accuracy.
Abstract: Historically, the investigations of electromyography (EMG) pattern recognition-based classification of intentional movements for control of multifunctional prostheses have adopted the filter cut-off frequency and sampling rate that are commonly used in EMG research fields. In practical implementation of a multifunctional prosthesis control, it is desired to have a higher high-pass cut-off frequency to reduce more motion artifacts and to use a lower sampling rate to save the data processing time and memory of the prosthesis controller. However, it remains unclear whether a high high-pass cut-off frequency and a low-sampling rate still preserve sufficient neural control information for accurate classification of movements. In this study, we investigated the effects of high-pass cut-off frequency and sampling rate on accuracy in identifying 11 classes of arm and hand movements in both able-bodied subjects and arm amputees. Compared to a 5-Hz high-pass cut-off frequency, excluding the EMG components below 60 Hz decreased the average accuracy of 0.1% in classifying the 11 movements across able-bodied subjects and increased the average accuracy of 0.1 and 0.4% among the transradial (TR) and shoulder disarticulation (SD) amputees, respectively. Using a 500 Hz instead of a 1-kHz sampling rate, the average classification accuracy only dropped about 2.0% in arm amputees. The combination of sampling rate and high-pass cut-off frequency of 500 and 60 Hz only resulted in about 2.3% decrease in average accuracy for TR amputees and 0.4% decrease for SD amputees in comparison to the generally used values of 1 kHz and 5 Hz. These results suggest that the combination of sampling rate of 500 Hz and high-pass cut-off frequency of 60 Hz should be an optimal selection in EMG recordings for recognition of different arm movements without sacrificing too much of classification accuracy which can also remove most of motion artifacts and power-line interferences for improving the performance of myoelectric prosthesis control.

Journal ArticleDOI
TL;DR: An MR image-based computational model of a murine KHT sarcoma is presented that allows the calculation of plasma fluid andsolute transport within tissue and suggests that plasma fluid transport is more sensitive to parameter changes than solute transport due to the dominance of transvascular exchange.
Abstract: An MR image-based computational model of a murine KHT sarcoma is presented that allows the calculation of plasma fluid and solute transport within tissue. Such image-based models of solid tumors may be used to optimize patient-specific therapies. This model incorporates heterogeneous vasculature and tissue porosity to account for nonuniform perfusion of an MR-visible tracer, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was conducted following intravenous infusion of Gd-DTPA to provide 1 h of tracer-concentration distribution data within tissue. Early time points (19 min) were used to construct 3D K(trans) and porosity maps using a two-compartment model; tracer transport was predicted at later time points using a 3D porous media model. Model development involved selecting an arterial input function (AIF) and conducting a sensitivity analysis of model parameters (tissue, vascular, and initial estimation of solute concentration in plasma) to investigate the effects on transport for a specific tumor. The developed model was then used to predict transport in two additional tumors. The sensitivity analysis suggests that plasma fluid transport is more sensitive to parameter changes than solute transport due to the dominance of transvascular exchange. Gd-DTPA distribution was similar to experimental patterns, but differences in Gd-DTPA magnitude at later time points may result from inaccurate selection of AIF. Thus, accurate AIF estimation is important for later time point prediction of low molecular weight tracer or drug transport in smaller tumors.

Journal ArticleDOI
TL;DR: The main conclusions of this study are that the local strain in the alveolar wall can reach a multiple of the value of the global strain, for simulations up to four times as high and that thin structures obviously cause hotspots that are especially at risk of overstretching.
Abstract: Mechanical ventilation is not only a life saving treatment but can also cause negative side effects. One of the main complications is inflammation caused by overstretching of the alveolar tissue. Previously, studies investigated either global strains or looked into which states lead to inflammatory reactions in cell cultures. However, the connection between the global deformation, of a tissue strip or the whole organ, and the strains reaching the single cells lining the alveolar walls is unknown and respective studies are still missing. The main reason for this is most likely the complex, sponge-like alveolar geometry, whose three-dimensional details have been unknown until recently. Utilizing synchrotron-based X-ray tomographic microscopy, we were able to generate real and detailed three-dimensional alveolar geometries on which we have performed finite-element simulations. This allowed us to determine, for the first time, a three-dimensional strain state within the alveolar wall. Briefly, precision-cut lung slices, prepared from isolated rat lungs, were scanned and segmented to provide a three-dimensional geometry. This was then discretized using newly developed tetrahedral elements. The main conclusions of this study are that the local strain in the alveolar wall can reach a multiple of the value of the global strain, for our simulations up to four times as high and that thin structures obviously cause hotspots that are especially at risk of overstretching.

Journal ArticleDOI
TL;DR: The development of dissociation constant (Kd) determination for protein–protein interaction and cell-based high-throughput screening (HTS) assay in SUMOylation cascade using FRET technology is reported.
Abstract: Forster resonance energy transfer (FRET) tech- nology has been widely used in biological and biomedical research and is a very powerful tool in elucidating protein interactions in many cellular processes. Ubiquitination and SUMOylation are multi-step cascade reactions, involving multiple enzymes and protein-protein interactions. Here we report the development of dissociation constant (Kd) determination for protein-protein interaction and cell-based high-throughput screening (HTS) assay in SUMOylation cascade using FRET technology. These developments are based on steady state and high efficiency of fluorescent energy transfer between CyPet and YPet fused with SUMO1 and Ubc9, respectively. The developments in theoretical and experimental procedures for protein inter- action Kd determination and cell-based HTS provide novel tools in affinity measurement and protein interaction inhibitor screening. The Kd determined by FRET between SUMO1 and Ubc9 is compatible with those determined with other traditional approaches, such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). The FRET-based HTS is pioneer in cell-based HTS. Both Kd determination and cell-based HTS, carried out in 384-well plate format, provide powerful tools for large-scale and high-throughput applications.

Journal ArticleDOI
TL;DR: The results show that SFDI is capable of revealing quantitative functional contrast in an AD model and may be a useful method for studying dynamic alterations in AD neural tissue composition and physiology.
Abstract: Extensive changes in neural tissue structure and function accompanying Alzheimer’s disease (AD) suggest that intrinsic signal optical imaging can provide new contrast mechanisms and insight for assessing AD appearance and progression. In this work, we report the development of a wide-field spatial frequency domain imaging (SFDI) method for non-contact, quantitative in vivo optical imaging of brain tissue composition and function in a triple transgenic mouse AD model (3xTg). SFDI was used to generate optical absorption and scattering maps at up to 17 wavelengths from 650 to 970 nm in 20-month-old 3xTg mice (n = 4) and age-matched controls (n = 6). Wavelength-dependent optical properties were used to form images of tissue hemoglobin (oxy-, deoxy-, and total), oxygen saturation, and water. Significant baseline contrast was observed with 13–26% higher average scattering values and elevated water content (52 ± 2% vs. 31 ± 1%); reduced total tissue hemoglobin content (127 ± 9 μM vs. 174 ± 6 μM); and lower tissue oxygen saturation (57 ± 2% vs. 69 ± 3%) in AD vs. control mice. Oxygen inhalation challenges (100% oxygen) resulted in increased levels of tissue oxy-hemoglobin (ctO2Hb) and commensurate reductions in deoxy-hemoglobin (ctHHb), with ~60–70% slower response times and ~7 μM vs. ~14 μM overall changes for 3xTg vs. controls, respectively. Our results show that SFDI is capable of revealing quantitative functional contrast in an AD model and may be a useful method for studying dynamic alterations in AD neural tissue composition and physiology.

Journal ArticleDOI
TL;DR: A finite element model that simulates the skin of the anterior forearm and posterior upper arm under a rich set of three-dimensional deformations and shows that using only in-plane experimental data in the parameter optimization results in a poor prediction of the out-of-plane response.
Abstract: Determining the mechanical properties of an individual’s skin is important in the fields of pathology, biomedical device design, and plastic surgery. To address this need, we present a finite element model that simulates the skin of the anterior forearm and posterior upper arm under a rich set of three-dimensional deformations. We investigated the suitability of the Ogden and Tong and Fung strain energy functions along with a quasi-linear viscoelastic law. Using non-linear optimization techniques, we found material parameters and in vivo pre-stresses for different volunteers. The model simulated the experiments with errors-of-fit ranging from 13.7 to 21.5%. Pre-stresses ranging from 28 to 92 kPa were estimated. We show that using only in-plane experimental data in the parameter optimization results in a poor prediction of the out-of-plane response. The identifiability of the model parameters, which are evaluated using different determinability criteria, improves by increasing the number of deformation orientations in the experiments.

Journal ArticleDOI
TL;DR: This study provides a new mouse model that can be used to quantitatively examine mechanical development, as well as compositional and structural changes and biological mechanisms, during post-natal tendon development.
Abstract: During post-natal development, tendons undergo a well orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but in this case, a mechanically inferior tendon is produced. As a result, the process of development has been postulated as a potential paradigm through which improved adult tissue healing may occur. In this study we measured the mechanical, compositional, and structural properties in the post-natal mouse Achilles tendon at 4, 7, 10, 14, 21, and 28 days old. Throughout post-natal development, the mechanical properties, collagen content, fibril diameter mean, and fibril diameter standard deviation increased. Biglycan expression decreased and decorin expression and fiber organization were unchanged. This study provides a new mouse model that can be used to quantitatively examine mechanical development, as well as compositional and structural changes and biological mechanisms, during post-natal tendon development. This model is advantageous due to the large number of genetically modified mice and commercially available assays that are not available in other animal models. A mouse model therefore allows future mechanistic studies to build on this work.