bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI Based Quantification of Outflow Boundary Conditions for Computational Fluid Dynamics of Stenosed Human Carotid Arteries
Authors: Groen Harald C. , Simons Lenette , Bosboom E. Marielle H. , van de Vosse Frans , van der Steen Anton F. W. , van der Lugt Aad , Gijsen Frank J. H. , Wentzel Jolanda J.
Published: July 2013

Many studies have been performed to investigate the contribution of wall shear stress (WSS) to pathophysiological processes related to atherosclerosis (Groen, et al., 2007; Kaazempur-Mofrad, et al., 2004; Ku, et al., 1985). To investigate these relationships in stenosed human carotid arteries, accurate assessment of WSS is required. WSS can be calculated in vivo by coupling medical imaging and computational fluid dynamics (CFD). However, often patient specific in- and outflow information is unavailable. Therefore flow through the common (CCA), internal (ICA) and external (ECA) carotid artery needs to be estimated. Murray’s law (Murray, 1926) is often used for that purpose, but it is unclear whether this law holds for stenosed arteries. The goal of this study was to determine outflow boundary conditions for WSS calculations in stenosed carotid bifurcations. Therefore we first quantified the flow (Q) in carotid arteries with different degrees of area stenosis using phase-contrast MRI and determined an empirical relation between outflow-ratios and degree of area stenosis. Secondly we compared the estimated flow ratio based on Murray’s law to the ones measured by MRI. Finally we analyzed the influence of the outflow conditions on the calculated WSS using CFD.
A Method to Extract the Complete Fiber Network Topology of Planar Fibrous Tissues and Scaffolds
Authors: D’Amore Antonio , Stella John A. , Wagner William R. , Sacks Michael S.
Published: July 2013

Improving fabrication protocols and design strategies, investigating on how fibrous ECM and synthetic architectures affect cell morphology, metabolism and phenotypic expression, predicting mechanical behaviors, have increasingly become crucial goals in the understanding of native tissues and in the development of engineered tissue. In the present study, an image-based analysis approach that provides an automatic tool to fully characterize engineered tissue fiber network topology was developed. The following micro architectural features were detected: fiber angle distribution, fiber connectivity, fiber overlap spatial density, and fiber diameter. In order to demonstrate the potential of this approach Electrospun poly(ester urethane)urea (ES-PEUU) scaffolds were studied. Electrospun scaffolds were chosen for their recognized capability to recapitulate native soft tissue extra cellular matrix (ECM) morphology.
Analysis of Coronary Sinus Motion and Cross-Sectional Area Using Cine MRI
Authors: Watson Pierre , Suever Jonathan , Oshinski John
Published: July 2013

To quantify periods of low motion of the coronary veins during the cardiac cycle. Coronary magnetic resonance venograms (cMRV) require that images be acquired during periods of low motion.
Computational Modeling of Aerosol Deposition Characteristics in Cyclic Bifurcating Tube Flow
Authors: Hyun Sinjae , Moon Sun Jin , Kim Chong S.
Published: July 2013

An accurate model of the human respiratory system allows health scientists to gain insight into the interactions between particulate matter (PM) and the exposed surfaces of the lung airways. Respiratory dose simulations and modeling are frequently used for evaluating health effects of inhaled toxic substances [1–4] and for analyzing the risk potentials of inhaled toxic or harmful PM such as vehicle emissions [4,5]. Pharmaceutical companies and pulmonologists find it useful in evaluating efficacy of inhaled medicinal aerosols and devising new patient treatment regimen [6–8], especially in vulnerable population groups such as children, industrial workers, and the elderly [10]. Recently, the respiratory system has seen increased attention as a possible venue for drug delivery to fight diseases such as AIDS, diabetes, and various cancers, among others. Computational fluid dynamics modeling and simulation continues to be an important tool for understanding of delivery of pharmaceutical aerosols to the lung airways and thereby improving treatment of airway disease, particularly, asthma with bronchodilators and corticosteroids inhalers [11,12].
Probing Mechanisms of Mechano-Sensitive Differentiation in Mesenchymal Stem Cells
Authors: Engler Adam J.
Published: July 2013

Adult mesenchymal stem cells (MSCs) have recently been shown to be responsive to the properties of their adjacent extracellular niche, most notably physical parameters such as topography and elasticity. Elasticity varies dramatically between tissues that MSCs inhibit, which drives elasticity-based differentiation into neurons, muscle, bone, etc. However within tissues, distinct elasticity gradients, brought on by pathological conditions, e.g. myocardial infarction ∼ 8.67 ± 1.50 kPa/mm, or through normal tissue variation, e.g. 0.58 ± 0.88 kPa/mm, could drive MSC migration. In fact, MSCs appear to undergo directed migration up elasticity gradients, or “durotax,” as shallow as 0.96 kPa/mm, indicating a ‘differentiation hierarchy’ since when given the choice, MSCs will durotax into the stiffest regions of the niche and then differentiate based on niche elasticity. As cells move up the gradient, they do so by deforming their niche to determine it’s elasticity, but the molecular mechanism that converts this biophysical signal into a biochemical one which the nucleus can interpret is yet unresolved. We have identified several focal adhesion-related proteins may be capable of force-induced conformational changes, e.g. vinculin. Upon the application of different amounts of traction stress in situ by MSCs, an appropriate amount of stretching results in the exposure of cryptic MAPK binding sites within vinculin and suggests that vinculin, among other focal adhesion proteins, may be sensitive to physical ECM properties and thus able to relay information leading to differentiation of stem cells.
A Simple, Cost-Effective Method to Improve Cell Viability in Microniche Culture Systems
Authors: Mignone Lindsay F. , Masand Shirley , Zahn Jeffrey D. , Shreiber David I.
Published: July 2013

Microfluidic networks are increasingly used to generate custom microenvironmental niches for cell culture and assays of cellular behavior. Perfusion systems are typically required to overcome diffusive limitations associated with culturing cells longer than a few hours when nutrient delivery, oxygen delivery and metabolic waste removal are required to maintain cell viability. In addition to the added complexity of experimental methods, perfusion systems can result in nonuniform nutrient delivery and subject cells to shear stresses, which may alter cell behavior and possibly cause cell death. In particular, when culturing cells within hydrogel scaffold-filled networks, as may be done in micro-tissue engineering, the need for perfusion culture also increases the likelihood of a destructive bubble entering the network. Moreover, analysis of micro-cultures frequently entails labelling with antibodies and/or fluorescent probes, which again requires controlled perfusion of the various reagents through the network. We have developed a simple technique to preserve cell viability and simplify labeling within microscale cultures without the need for perfusion. Instead of bonding a microfluidic network to glass, PDMS, or another impermeable substrate, the network is bonded to a semi-permeable microdialysis membrane, which allows free exchange of oxygen, proteins, nutrients, and waste between the microfluidic channels and culture media in static culture plates.
Enhanced Oxygen Delivery to Liver Tissue Equivalent by Perfluorocarbon
Authors: Shi Gengbei , Coger Robin N.
Published: July 2013

Bioartificial Liver Devices (BALs) have the potential to serve as a bridge strategy for patients awaiting liver transplants, and also show promise as drug testing platforms for the pharmaceutical industry [1]. Yet the limitations of O2 transport through the 3D tissue structures of current designs continue to present engineering challenges. In previous work our group successfully improved O2 availability for hepatocytes by introducing micropathways within the BAL’s cellular space [3–5]. The current study investigates the benefits of increasing O2 availability of the flow medium via perfluorocarbons (PFCs). PFCs were chosen since they have demonstrated effectiveness in increasing the overall oxygen solubility of their carrier liquids, e.g., artificial blood [2]. The study seeks to clarify the effects of PFCs on hepatocyte viability and functional performance under various culture conditions.
Gene Expression Profiles of Arterial Endothelial Cells in Response to Increased Shear Stress In Vivo
Authors: Zhang Ji , Burridge Kelley A. , Friedman Morton H.
Published: July 2013

Endothelial cells in vivo are believed to adapt to local hemodynamics in regions with largely unidirectional flow [1] and develop a quiescent phenotype. However, the local shear stress is altered occasionally by changes in global hemodynamic variables, such as heart rate and flow rate. These changes are caused by a number of normal physiologic events, such as exercise, smoking, sleep, stress and digestion. The duration of these changes ranges from minutes to hours, and endothelial cells undergo structural remodeling and phenotypic transformation in order to adapt to the altered shear stress. During the adaptive response, the dynamics of endothelial phenotypic change adds a new dimension to the endothelial response to shear stress.
A Nonlinear Biphasic Model for Mass Transport During Constant Flow-Rate Infusion Into Brain Tissue
Authors: Smith Joshua H. , García José Jaime
Published: July 2013

Convection-enhanced delivery is a means to deliver therapeutic agents directly into brain tissue. Biphasic models have been used to study the concomitant fluid and mass transport that occurs during infusion, however previous studies have been limited by the assumption of linear elasticity of the solid phase [1]. In contrast, nonlinear stress-strain curves have been documented for brain tissue under finite deformation in tension and compression [2, 3].
Influence of Heart Rate and Contractility on Coronary Diagnostic Parameters With Normal Microvasculature in Porcine Model
Authors: Kolli Kranthi K. , Effat Mohamed , Helmy Tarek , Leesar Massoud , Imran Arif , Peelukhana Srikara V. , Schneeberger Eric W. , Hand Dwight , Gottliebson William , Succop Paul , Banerjee Rupak K.
Published: July 2013

Invasive guide-wire measurements are used to assess coronary lesion severity under clinical settings. The objective of the present research is to determine the influence of heart rate (HR) and contractility (CY) on fractional flow reserve (FFR; the ratio of distal pressure to proximal pressure at a stenotic section) and pressure drop coefficient (CDPe; the ratio of trans-stenotic pressure drop to distal dynamic pressure). In-vivo experiments were performed on eight Yorkshire pigs, to evaluate the diagnostic parameters for the conditions “CY<1100 mmHg/sec” and “CY>1100 mmHg/sec,” and for the conditions “HR<110 bpm” and “HR>110 bpm”. It was found that in the presence of normal microvasculature the measured coronary diagnostic parameters (FFR and CDPe) have a significant mean difference for variation in contractility (0.59±0.04 to 0.89±0.045 for FFR and 121.63±18 to 23.53±18 for CDPe). The variation in HR has no significant effect on FFR and CDPe (0.72±0.048 to 0.74±0.048 and 54±20 to 53±20 respectively).
Gender-Specific Transfer Functions Might Give More Accurate Estimates of Central Pressure
Authors: Mookerjee Ashis , Al-Jumaily Ahmed M. , Lowe Andrew , Westerhof Berend E.
Published: July 2013

This study investigates whether individualized transfer functions for estimating central pressures can be derived based on statistical information on the physical properties of the forearm vasculature. Physical parameters of the uniform thin walled artery model are assigned based on clinical measurements and invasive pressure measurements (n = 20) are used to calculate the effective peripheral load. The calculated load is parameterized by a Windkessel model and the variation of the Windkessel parameters is analyzed with gender, age and height. Whilst there is high spread and poor correlation of the data with age and height, there is clear clustering of data with gender. This suggests that model parameters are significantly different in either gender, and gender-specific transfer functions might be more appropriate for accurate reconstruction of central pressure.
From Human Liver Vascular Corrosion Cast to Electrical Analog Model of the Hepatic Blood Flow
Authors: Debbaut C. , Monbaliu D. , Casteleyn C. , Cornillie P. , Van Loo D. , Masschaele B. , Pirenne J. , Simoens P. , Van Hoorebeke L. , Segers P.
Published: July 2013

Machine perfusion (MP) is experiencing a revival in organ preservation due to the limitations of static cold storage and the need for better preservation methods for expanded criteria donors. Liver MP prototypes, however, face problems such as potential damage to sinusoidal endothelial cells, and heterogeneous perfusion related to the complex hepatic microcirculation.
Regurgitant Commissure Flow Through a Closed Polymeric Heart Valve
Authors: Corbett Scott C. , N.-Hashemi Hamid , Coskun Ahmet U.
Published: July 2013

While heart valve prostheses have been used successfully since 1960, outcomes are far from ideal. The underlying problem with bioprostheses is a limited life from structural changes such as calcification and leaflet wear, leading to valve failure. The underlying problem with mechanical heart valves is the presence of flow disturbances which necessitate anticoagulation. A polyurethane valve has the potential to improve upon the shortcomings of existing valves and ultimately improve patient survival.
The Biophysical Response of Collagen-Fibrin Composite Gels to In Vitro Acupuncture
Authors: Julias Margaret , Buettner Helen M. , Shreiber David I.
Published: July 2013

Therapeutic acupuncture involves the insertion and manipulation of fine needles at specific points. Although acupuncture has been proven effective for a number of conditions, the mechanisms that underlay these effects remain unknown. A critical first step is to identify the local changes that occur during needle manipulation, which can then be related to longer-term and more remote consequences. In vivo and ex vivo studies have demonstrated that loose collagenous subcutaneous connective tissue couples to needles during therapeutic manipulation, which deforms the tissue and exposes resident cells to altered mechanics and triggers morphologic and phenotypic changes. The resultant alignment of the tissue and cells may additionally help to propagate signals along acupuncture meridians.
Collapse Temperature of Solutions Important for Lyopreservation of Living Cells at Ambient Temperature
Authors: Yang Geer , Gilstrap Kyle , Zhang Aili , Xu Lisa X. , He Xiaoming
Published: July 2013

With recent advances in cell-based medical technologies such as tissue engineering and regenerative medicine, living cells are becoming more and more important as a therapeutic tool in modern medicine. Due to the limited availability of cell sources, effective long-term preservation of living cells is of great importance to the eventual success of these emerging technologies. Cell preservation can be achieved by cooling/freezing the cells to a cryogenic temperature (cryopreservation) and/or drying the cells to preserve at ambient temperature (lyopreservation). Due to the high cost of maintaining and inconvenience of transporting cryopreserved cells, there is an increasing demand for cell lyopreservation.
Dynamics of TNF Capture Within Hemoadsorption Beads Used to Treat Sepsis
Authors: Kimmel Jeremy D. , Lacko Christopher S. , Delude Russell L. , Federspiel William J.
Published: July 2013

Sepsis is a serious medical condition characterized by systemic inflammation caused by infection, and affects more than 750,000 individuals per year in the US, with a mortality rate of approximately 30% [1]. The pathophysiology of sepsis is complex and not entirely understood, but is believed to be related to the dysfunction of multiple interdependent humoral mediator pathways, including redundant release of inflammatory cytokines [2]. Removal of both pro- and anti-inflammatory cytokines from the circulating blood is believed to be a promising therapy for severe sepsis [3]. We are developing an extracorporeal hemoadsorption device to remove cytokines from the blood using a novel, biocompatible, sorbent bead technology. In this work, we examined the adsorption dynamics of tumor necrosis factor (TNF) within hemoadsorption beads using packed bed capture experiments and fast protein liquid chromatography (FPLC).
Effect of TGF-β3 on the Gene Expression of Intervertebral Disc Cells in 3D Pellet Cultures
Authors: Houseman C. , Scro M. , Belverud S. , Chen D. , Razzano P. , Levine M. , Grande D. A. , Chahine N. O.
Published: July 2013

Intervertebral disc (IVD) degeneration typically involves changes in the multiple constitutive tissues of the IVD. Many tissue repair efforts have focused on the use of differentiated disc cells or stem cells for the regeneration of an IVD in vitro. Consequently, successful long term culture of human disc cells is pivotal for tissue regeneration of the IVD. The aim of this study is to establish a long-term in vitro culture system for the growth of disc cells that maintain their phenotype based on the anatomical origin (annulus fibrosus (AF), nucleus pulposus (NP), or the vertebral end-plates (EP)). This maintenance of phenotype is crucial for examination of treatment efficacy, which is typically designed to induce regeneration of a single tissue type (i.e. injection of growth factors into the NP or anti-inflammatory treatment of the EPs).
Treatment of Intervertebral Disc With Chondroitinase-ABC Results in Reversible Degeneration in Rat Tail Model
Authors: Houseman C. , Chen D. , Scro M. , Grande D. A. , Levine M. , Chahine N. O.
Published: July 2013

Injury models of intervertebral disc provide a strong tool for studying the etiology of degenerative disc disease. Enzymatic degradation of the IVD with injection of chondroitinase ABC (ChABC) has been used in models of disc injury in rats, rabbits and goats [1–3], as well as used to induce repair of herniated discs in rabbits via chemonucleolysis [4, 7]. In a recent study, we investigated the dose effect of ChABC dosage on inducing disc degeneration [5]. Consistent with previous studies, our results found that a low dosage of ChABC (0.1 U/ml) resulted in decreased mechanical properties and glycosaminoglycan (GAG) content by 4 weeks post injections. Interestingly, when the dosage was increased to 10 U/ml, results indicated no measurable difference in GAG content or compressive mechanical properties after 4 weeks compared to sham saline injection or intact controls. These findings suggested that rat IVD was either unaffected by the enzymatic injection, or that it was capable of mounting a repair process after degradation with ChABC.
The Effects of Cell Contraction and Loss of Adhesion on the Apoptosis of Valve Interstitial Cells
Authors: Zhao Ruogang , Lin Lina , Simmons Craig A.
Published: July 2013

Dystrophic calcification in sclerotic aortic valves is associated with apoptosis of myofibroblasts that differentiate from valve interstitial cells (VICs). The factors that regulate apoptosis in sclerotic valves are not known, but may include mechanical stimuli, as is the case in other fibrotic tissues. In support of this hypothesis, we have observed that VICs on stiff collagen matrices that simulate fibrotic tissue differentiate to myofibroblasts and form calcified aggregates that contain apoptotic cells [1]. However, the mechanisms by which cell aggregation leads to VIC apoptosis are unknown. In other cell types, cell contraction caused by release of matrix tension can induce cell apoptosis, but the mechanical transduction pathway regulating this process is unknown [2]. Similarly, cell rounding caused by disrupting the cytoskeletal network has been found to induce apoptosis [3], indicating the cytoskeletal network may play an important role in the cell shape-change related apoptosis pathways. Loss of adhesion between the cell and its matrix is also a well-documented cause for apoptosis of adherent cell types [4].
A Multiscale Mixture Model for Polymer Degradation and Erosion
Authors: Soares João A. , Zunino Paolo
Published: July 2013

Over the last 50 years, biodegradable materials have found a wide variety of applications in the medical field ranging from biodegradable sutures, pins and screws for orthopedic surgery, implants for local drug delivery, tissue engineering scaffolds, and biodegradable endovascular and urethral stents. The ability to predict the evolution of biodegradable polymers over the course of degradation would enhance the biodegradable implant design process. Polymer degradation is the irreversible chain scission process that breaks polymer chains down to oligomers and finally monomers. Extensive degradation leads to erosion, which is the process of material loss from the polymer bulk. Such materials can be monomers, oligomers, parts of the polymer backbone, or even parts of the polymer bulk. Hence, degradation and erosion are distinct but related process.
Study of Beloussov’s Hyper-Restoration Hypothesis for Regulation of Embryonic Heart Bending
Authors: Ramasubramanian Ashok , Taber Larry A.
Published: July 2013

During cardiac c-looping, an important developmental phase in early heart development, the initially straight heart tube (HT) is transformed into a c-shaped tube. Two distinct processes, ventral bending and dextral rotation, constitute c-looping. Previous research suggests that ventral bending is likely driven by forces that are intrinsic to the heart while dextral rotation is driven by forces applied by a pair of omphalomesenteric veins that flank the heart tube and a membrane called the splanchnopleure that lies on top of the heart.
Mechanical Compression Affects Nutritional Transport in Human Intervertebral Disc
Authors: Jackson Alicia R. , Yuan Tai-Yi , Huang Chun-Yuh , Gu Wei Yong
Published: July 2013

Although the exact cause is not clear, low back pain has been attributed to degeneration of the intervertebral disc (IVD) of the spine, which has been linked to poor nutritional supply to the disc. Because the IVD is the largest avascular structure in the human body, disc cells must rely on diffusional transport for delivery of important nutrients, such as oxygen and glucose, from the surrounding vasculature. Thus, understanding factors affecting nutritional supply to the cells is important in elucidating the etiology of disc degeneration and related back pain. While knowledge of how mechanical strain affects nutritional transport is important in understanding these phenomena, little can be found in the literature regarding strain-dependent diffusion of nutrients in human IVD.
Numerical Modelling of Blood Flow in the Mouse Aortic Arch Using Inflow Velocities Obtained by Phase-Contrast MRI
Authors: Kazakidi Asimina , Wylezinska Marzena , Bohraus Yvette , Van Doormaal Mark , Tremoleda Jordi L. , Gsell Willy , Weinberg Peter D. , Ethier C. Ross
Published: July 2013

Atherosclerotic lesions have a highly non-uniform distribution in regions of arterial branching and curvature, consistent with hemodynamic factors, in particular wall shear stress (WSS), controlling their development. The widespread and increasing use of the mouse as a model for studying atherosclerosis has encouraged investigation of the hemodynamics of the mouse aortic arch [1–3], in which previous studies have revealed areas of high and low lesion prevalence and variation in the expression of pro-atherogenic molecules [4]. Our previous computational simulations [1–2] did not produce distributions of WSS that explain the pattern of lesions. We are currently investigating whether incorporation of more realistic aortic root velocity measurements, obtained using phase-contrast magnetic resonance imaging (PC-MRI), into these simulations can improve the correlation with disease. Here we present velocities obtained by PC-MRI and preliminary simulations employing the data.
In-Vitro Thrombogenicity Assessment of Mechanical Circulatory Support Devices and Prosthetic Heart Valves
Authors: Claiborne Thomas E. , Girdhar Gaurav , Sheriff Jawaad , Jesty Jolyon , Slepian Marvin J. , Benkowski Robert , Pinchuk Leonard , Bluestein Danny
Published: July 2013

Mechanical circulatory support (MCS) devices developed for end-stage heart failure or as a bridge-to-transplant include total artificial hearts (TAH) and ventricular assist devices (VAD) and utilize prosthetic heart valves (PHV) or rotary impellers to control blood recirculation [1]. These devices are currently not optimized to reduce the incidence of pathological flow patterns that cause elevated stresses leading to platelet activation and thrombosis. Although the latter is partially mitigated by lifelong anticoagulation therapy, it dramatically increases the risk of uncontrolled bleeding. For instance thromboembolic stroke-related complications (∼2%) were relatively less with the TAH-t compared to uncontrolled bleeding due to anticoagulation use (∼20%) [2]. Platelet activation should therefore be quantified and optimized based on patient-specific cardiac outputs in device prototypes before clinical use.
The Inflation Response of Mouse Sclera: Age Effects on the Mechanical Properties of Scleral Tissue
Authors: Myers Kristin M. , Cone Frances , Quigley Harry , Coudrillier Baptiste , Nguyen Thao D.
Published: July 2013

The mouse model offers an opportunity to investigate how alterations to the connective soft tissue contribute to the development of disease through the study of transgenic and diseased mouse strains. For example, by measuring the deformation response of the eye wall to increases in pressure of these different mouse types, the possible role of ocular tissue material properties in glaucomatous damage can be determined. Glaucoma is one of the leading causes of blindness in the United States and in the world with an estimate of 60 million people affected by this year [1]. It is caused by damage to the retinal ganglion cells (RGC), a type of neuron that transmits visual information to the brain. Despite therapeutic efforts to reduce the rate of vision loss in glaucoma patients, the rate of blindness remains high [2]. There is evidence that elevated intraocular pressure (IOP) is a strong risk factor for the disease [3–5], and it is hypothesized that possible alterations in the time-dependent scleral material properties may play an important role in cumulative RGC death.
A Multiscale Model for the Indentation of Type-I Collagen Soft Tissue Equivalents
Authors: Hadi Mohammad F. , Delalondre Fabien J. , Smith Cameron W. , Zhang Lijuan , Shephard Mark S. , Barocas Victor H.
Published: July 2013

Indentation has become a popular research technique for the mechanical characterization of collagen-based soft tissues. The popularity of the method stems from its requirement of a modestly sized sample, from its ability to be applied in vitro as well as in vivo, and from the ready availability of instrumentation and analytical techniques borrowed from a long tradition of its application to non-biological materials. Many analytical models for the indentation of collagen-based soft tissues rely on a Hertzian contact model. Such a model emphasizes the contributions of an idealized material in compression over the contributions of the material in tension. However, this approach largely neglects the role of the collagen microstructure in soft tissue that has the capacity to carry far greater mechanical loads in tension rather than in compression.
Water-Fat Decomposition by IDEAL-MRI With Phase Estimation: A Method to Determine Chemical Contents In Vivo
Authors: Xu Jing , Hu Xiaofei , Tang Haiying , Kennan Richard , Azer Karim
Published: July 2013

High-resolution Magnetic Resonance Imaging (MRI) of humans and animals in vivo is routine and non-invasive. Identifying and quantifying chemical composition of tissue from acquired images is a challenge. MR spectroscopy (MRS) may be used to identify chemical components accurately over a finite volume in the tissue. However, the temporal and spatial resolutions are limited. Multi-spectral MRI exploits the multiple modes of MR such as T1, T2 and proton density maps and classifies voxels into different tissue types, but the chemical identity of the tissue remains unknown. Many fat suppression methods were developed because the unwanted fat signal often compromises image interpretability in clinical MRI, but these techniques are sensitive to MR field inhomogeneity. Multi-point Dixon methods separate MR images into water and fat images and are less sensitive to field inhomogeneity [1] and IDEAL-MRI (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) improved upon the Dixon methods by avoiding the problem of phase unwrapping [2]. However, special care has to be taken when estimating the field map to avoid erroneous solutions to the least-squares estimation problem which lead to artifacts such as swapping of water and fat. The use of region growing schemes (with a reliable seed) mitigates this problem as demonstrated in previous studies [3][4]. However, the seed is not always reliable and growing schemes can be sensitive to phase discontinuities. Moreover, although the technology was successfully demonstrated on many clinical scanners, only limited applications were found in preclinical scanners with high MR field where the field inhomogeneity can be far worse [5]. We developed a robust and accurate algorithm to compute water and fat content on an 11.7T small animal scanner by improving upon existing phase estimation methods through multiple starting pixels and consensus-based region growing. The method, after further validation, has the potential of providing a translatable assay to study disease progression and regression related to fat and water contents in various animal models, such as studying atherosclerotic plaque composition.
A Fluid Structure Interaction Approach for Patient Based Abdominal Aortic Aneurysm Rupture Risk Prediction
Authors: Xenos Michalis , Rambhia Suraj , Alemu Yared , Einav Shmuel , Ricotta John J. , Labropoulos Nicos , Tassiopoulos Apostolos , Bluestein Danny
Published: July 2013

Fluid structure interaction (FSI) simulations of patient-specific fusiform non-ruptured and contained ruptured Abdominal Aortic Aneurysm (AAA) geometries were conducted. The goals were: (1) to test the ability of our FSI methodology to predict the location of rupture, by correlating the high wall stress regions with the rupture location, (2) estimate the state of the pathological condition by calculating the ruptured potential index (RPI) of the AAA and (3) predict the disease progression by comparing healthy and pathological aortas.

The patient specific AAA FSI simulations were carried out with advanced constitutive material models of the various components of AAA, including models that describe wall anisotropy based on collagen fibers orientation within the arterial wall, structural strength of the aorta, intraluminal thrombus (ILT), and embedded calcifications. The anisotropic material model used to describe the wall properties closely correlated with experimental results of AAA specimens.

The results demonstrate that the anisotropic wall simulations showed higher peak wall stresses as compared to isotropic material models, indicating that the latter may underestimate the AAA risk of rupture. The ILT appeared to provide a cushioning effect reducing the stresses, while small calcifications (small-Ca) appeared to weaken the wall and contribute to the rupture risk. FSI simulations with ruptured AAA demonstrated that the location of the maximal wall stresses and RPI overlap the actual rupture region.
In Vitro Validation of Finite Element Model of AAA Hemodynamics Incorporating Realistic Outflow Boundary Conditions
Authors: Kung Ethan O. , Les Andrea S. , Medina Francisco R. , Wicker Ryan B. , McConnell Michael V. , Taylor Charles A.
Published: July 2013

Numerical methods have become a powerful tool to quantify hemodynamic forces in the cardiovascular system. Studying these forces enables us to understand cardiovascular disease mechanisms, as well as better evaluate and design cardiovascular medical devices. However, much work remains to validate numerical methods against experimental data. Vignon-Clementel and colleagues have shown that the boundary conditions (BCs) prescribed at the outlets of numerical domains dramatically influence the flow and pressure computational results [1]. While many in-vitro studies have implemented simple BCs to allow for acceptable validations of numerical methods, none has implemented BCs that provide physiologically realistic flows and pressures.
Design Optimization of a Mechanical Heart Valve for Reducing Valve Thrombogenicity: A Case Study With ATS Valve
Authors: Girdhar Gaurav , Alemu Yared , Xenos Michalis , Sheriff Jawaad , Jesty Jolyon , Einav Shmuel , Bluestein Danny
Published: July 2013

Flow past mechanical heart valves (MHV) in mechanical circulatory support devices including total artificial hearts and ventricular assist devices, is primarily implicated in thromboembolism due to non-physiological flow conditions where the elevated stresses and exposure times are sufficiently high to cause platelet activation and thrombus formation. Mitigation of this risk requires lifelong anticoagulation therapy and less thrombogenic MHV designs should therefore be developed by device manufacturers [1].
Serum and Urine Biomarker Elevation Indicating the Onset of Deep Tissue Injury as Examined on a Rat Model
Authors: Makhsous Mohsen , Pandya Atek , Modi Mauli , Reprogle Briana , Chadwick Christopher C. , Lin Fang
Published: July 2013

Deep tissue injury (DTI) is a serious pressure ulcer (PU) which initiates in deep tissue, mainly muscle, and progresses rapidly to a full-thickness wound [1, 2]. Therefore, an early indication should help in increasing awareness and providing prompt intervention to prevent it from progressing to an open wound, which is susceptible to infection and typically needs prolonged and aggressive care. However, the diagnosis of DTI is currently still vague at best[2] with only subjective tools. This situation calls for tools for objectively sensing the tissue changes while the skin is still intact, to allow development of evidence-based protocols for early diagnosis and treatment. Since DTI initiates from deep muscle layer around a bony prominence, a tool that sensitive to muscle damage may have the potential to objectively sense the onset of a DTI in clinical application. A number of molecular biomarkers have been reported in the literature as suitable for indicating muscle damage. Some of the most promising biomarkers are myoglobin and heart-type fatty acid binding protein (H-FABP). Myoglobin and H-FABP are two relatively small muscle proteins that show a very fast release time after skeletal muscle damage/necrosis when no myocardial infarction or damage is present; therefore, they may be used to identify skeletal muscle injury in DTI formation. The objective of this study was to initially test whether myoglobin and H-FABP in serum and urine respond quickly to pressure induced deep tissue injury on a rat model. It is expected that knowledge gained from this study may lead to a promising new methodology to sense the visually invisible DTI.
Estimation of Biomechanical Stimulus in Bone Scaffolds in Vivo: Multi-Scale Finite Element Model
Authors: Roshan-Ghias Alireza , Terrier Alexandre , Pioletti Dominique P.
Published: July 2013

Bone formation inside a scaffold is a complex process involving different phenomena, one of which being the mechanical stimulation (1,2). Our goal in bone tissue engineering is, through mechanical considerations, confer osteoinductivity to a synthetic bone scaffold.
Modeling of Osmotic Injury in Bovine Sperm During Desiccation
Authors: Sitaula Ranjan , Bhowmick Sankha
Published: July 2013

Although desiccation preservation offers promise as an alternative method for the preservation of mammalian cells, there has been limited success in achieving survival at very low water content [1]. Osmotic injury is one of the major damage factors during cellular dehydration. During the drying process, cells experience increased extracellular hypertonic environment as a result of evaporation of water. This factor coupled with the limited permeability of cell membranes leads to irreversible cellular damage. In the current study, we have studied the effect of hypertonic osmolality and exposure time on bovine sperm motility. The goal was to develop a theoretical osmotic damage model to predict motility loss during dehydration. Modeling was performed by using a first order rate equation. Motility data from the hypertonic exposure experiments were used to determine the first order reaction parameters and the cumulative osmotic damage (COD), which provided a measure of the extent of osmotic damage. The parameters were then used to predict motility of natural convection desiccation process. Experimental drying data was compared to the predicted data to determine the extent of osmotic damage.
Noninvasive Assessment of Diastolic Intraventricular Pressure Gradients in a Large General Population (the Asklepios Study)
Authors: Van Der Smissen Benjamin , Claessens Tom E. , Rietzschel Ernst R. , De Buyzere Marc L. , De Bacquer Dirk , Gillebert Thierry C. , Van Ransbeeck Peter , Verdonck Pascal R. , Segers Patrick
Published: July 2013

Accurate assessment of diastolic (dys)function by non-invasive techniques has important therapeutic and prognostic implications but remains a challenge to the cardiologist. A promising parameter to evaluate diastolic (dys)function more accurately is the early diastolic intraventricular pressure gradient (IVPGe) which is considered representative of the active relaxation of the left ventricle. It has been shown that IVPGe can be estimated non-invasively by measuring blood velocities along a base-to-apex scan line using color M-mode Doppler (CMD) echography [1]. Although this technique is known for about 20 years, IVPGe is still not used in daily clinical practice because its approach is complicated and too laborious [2].
In Vivo Echo-PIV Measurements of the Flow Within Abdominal Aortic Aneurisms (AAA)
Authors: Stocchino Alessandro , Palombo Domenico , Pane Bianca , Spinella Giovanni
Published: July 2013

The incidence of Abdominal Aortic Aneurysms (AAA) varies between 3% and 6% of the elder population, especially men over sixty years of age. Moreover, familiarity, smoking and peripherical atherosclerosis are known to be important risk factors. In the United States AAA ruptures cause about 9000 deaths every year. About 33000 elective surgical treatments per year are performer with a mortality of 1400–2800 patients. The percentage of success of surgical treatment remains strictly related to the diagnosis of the stage of the AAA. Mortality rate for elective surgical intervention (asymptomatic aneurysms) is 5%. On the contrary mortality rate for emergency surgical intervention is about 70% [1]. Selection of candidates to surgery is still based on measurement of aortic diameter, with a threshold size of 55 mm. The rate of AAA rupture increases from 21% to 46% for diameters between 50 and 70 mm. The main diagnostic tool currently adopted is the CT that allows for obtaining precise information regarding the dimensions and the morphology of the aneurysm and possible proximal extension (juxarenal, infrarenal, thorac-abdominal) and distal (iliac and hypogastric) of the aneurysm, intramural thrombus. Since rupture occurs when the aneurysm wall fails to withstand the forces acting on it, in vivo data on AAA wall pathology could identify patients at risk of rupture. End-stage aneurysm disease and especially aneurysm rupture are characterized by extensive inflammation of the arterial wall. Although the stimulus for this enhanced infiltration is not known, recent insights into the pathophysiology of aneurysm formation, growth, and rupture indicate a close relationship between increased mechanical stress and the activation of infiltrated lymphocytes and macrophages [2]. This increased inflammatory activity results in the progressive breakdown of the aortic wall, aneurysm dilatation and, ultimately, rupture. A further complication is represented by the mechanical actions exerted on the arterial wall by the internal blood flow. The blood flow is strongly influenced by the presence of an AAA, which modifies significantly the geometry of the aorta. Shear stresses and pressure are important factors to understand the formation and evolution of an AAA. Another important aspect is related to the formation of the thrombus that is thought to be relevant for the wall degeneration, see [3] for a comprehensive review of these topics.
Morpho-Functional Interaction Between Muscle and Tendon in Hypertrophic MLC/mIGF-1 Mice
Authors: Rizzuto E. , Musarò A. , Catizone A. , Del Prete Z.
Published: July 2013

Tendons and ligaments are uniaxial viscoelastic connective tissues and, during normal activity, tendons transmit forces from muscles to bones, while ligaments stabilize the joints. Many experiments have been carried out to study ligaments and tendons mechanical properties [1], and the effects of training protocols [2] or specific pathologies. Recently, different transgenic mice models have been proposed as a new way to study in depth tendons’ function and development [3]. Within this context, we made use of pathological and transgenic animal models to investigate the morpho-functional interaction between muscles with an altered functionality and their tendons. In a previous work, by using the animal model of human Duchenne dystrophy, mdx, we found out that tendons connected to muscles with functional defects present reduced mechanical properties and an altered balance between alive and dead cells [4]. Here, we evaluated whether hypertrophic muscles would also involve alterations in tendon biomechanical properties. To do this, we used the transgenic animal model MLC/mIgf-1, were the local form of Igf-1 is over-expressed under a muscle specific promoter [5] inducing an increase in skeletal muscle mass and a proportional increment of force. To determine tendons’ elastic and viscous response separately, complex compliance has been computed with a new experimental method [6] which uses a pseudorandom Gaussian noise (PGN) to stimulate all the frequencies of interest within its bandwidth. Elasticity determines the tissue response to loading while viscous dissipation affects the likelihood of injuries to tendons. Indeed, knowing tendinous tissue viscoelasticity is central to better understand the mechanism between energy dissipation and tissue injuries. Finally, the hypothesis that changes in tendons’ mechanical properties could be correlated with alterations in the balance between alive and dead cells has been tested with an in situ cellular analysis.
Response of an Actin Filament Network Model Under Cyclic Stretching Through a Coarse Grained Monte Carlo Approach
Authors: Kang John , Steward Robert L. , Kim YongTae , Schwartz Russell , Puskar Kathleen M. , LeDuc Philip R.
Published: July 2013

The cytoskeleton is a dynamic system linked to the cell’s environment through sites of potential mechanical interaction such as focal adhesions, integrins, cellular junctions, and the extracellular matrix. The physiologic mechanical stimulation experienced by cells such as endothelial cells is comprised of multiple mechanical modes (e.g., stretching and shear), thus presenting a challenge to characterize their influence on cell structure.
Effect of Ischemia and Reperfusion on Skeletal Muscle Damage
Authors: Loerakker Sandra , Manders Emmy , Strijkers Gustav J. , Baaijens Frank P. T. , Bader Dan L. , Nicolay Klaas , Oomens Cees W. J.
Published: July 2013

Sustained mechanical loading of soft tissues covering bony prominences, as experienced by bedridden and wheelchair-bound individuals, may cause skeletal muscle damage. This can result in a condition termed pressure-related deep tissue injury (DTI), a severe kind of pressure ulcer that initiates in deep tissue layers, and progresses towards the skin. Damage pathways leading to DTI can involve ischemia, ischemia/reperfusion injury, impaired lymphatic drainage, and sustained tissue deformation. Recently, we have provided evidence that in a controlled animal model, deformation is the main trigger for damage within a 2h loading period [1,2]. However, ischemia and reperfusion may play a more important role in the damage process during prolonged loading periods.
Visualization of Microcirculation Based on Brightness Variation in Contrast-Enhanced Ultrasound
Authors: Funamoto Kenichi , Hayase Toshiyuki , Kodama Tetsuya
Published: July 2013

Many studies have investigated effects of drug administration and gene transfer to treat tumors in small animal models. Microcirculation plays important roles in the development and growth of tissues; a tumor proliferates by angiogenesis [1], resulting in the formation of a dense microvasculature, while the microvasculature degenerates in locations where necrosis or apoptosis occurs. Hence, the growth of a tumor can be evaluated based on comprehension of the morphology of microcirculation. Enhanced visualizations of small blood vessels enabled by microbubbles or contrast agent have been reported. The maximum intensity persistence (MIP) method, which maintains the maximum brightness when the contrast agent passes through the vessel, is a representative visualization method already incorporated in existing ultrasonic equipment. However, the performance of the MIP method is deteriorated by changes of brightness due to in vivo movement accompanying heartbeat and breathing. Therefore, complicated processes are necessary to eliminate the effects of such movement by monitoring heartbeat with an echocardiogram (ECG) and by detecting breathing with a pressure sensor.
The Biomechanical Response of Normal and Glaucoma Human Sclera
Authors: Coudrillier Baptiste , Myers Kristin M. , Nguyen Thao D.
Published: July 2013

By 2010, 60 million people will have glaucoma, the second leading cause of blindness worldwide [1]. The disease is characterized by a progressive degeneration of the retinal ganglion cells (RGC), a type of neuron that transmits visual information to the brain. It is well know that elevated intraocular pressure (IOP) is a risk factor in the damage to the RGCs [3–5], but the relationship between the mechanical properties of the ocular connective tissue and how it affects cellular function is not well characterized. The cornea and the sclera are collage-rich structures that comprise the outer load-bearing shell of the eye. Their preferentially aligned collagen lamellae provide mechanical strength to resist ocular expansion. Previous uniaxial tension studies suggest that altered viscoelastic material properties of the eye wall play a role in glaucomatous damage [6].
A Continuum Approach to Introductory Biomechanics
Authors: Rossmann Jenn Stroud
Published: July 2013

An introduction to biomechanics based on a continuum mechanics approach is described. This approach introduces a spectrum of material behavior that has Hookean solids at one extreme, and Newtonian fluids at the other, with many interesting combinations such as biomaterials in between. By building progressively from one-dimensional to higher dimension formulations, this approach makes continuum concepts such as the Cartesian stress tensor accessible to early undergraduate students. From this gradual development of ideas, with many illustrative case studies interspersed, students develop both physical intuition for how bioengineering materials behave, and the mathematics used to describe this behavior.