Showing papers in "Annals of Biomedical Engineering in 2006"
TL;DR: The broad utility of superparamagnetic iron oxide nanoparticles in molecular imaging is illustrated, including some of the recent developments, such as the transformation of SPIO into an activatable probe termed the magnetic relaxation switch.
Abstract: The field of molecular imaging has recently seen rapid advances in the development of novel contrast agents and the implementation of insightful approaches to monitor biological processes non-invasively. In particular, superparamagnetic iron oxide nanoparticles (SPIO) have demonstrated their utility as an important tool for enhancing magnetic resonance contrast, allowing researchers to monitor not only anatomical changes, but physiological and molecular changes as well. Applications have ranged from detecting inflammatory diseases via the accumulation of non-targeted SPIO in infiltrating macrophages to the specific identification of cell surface markers expressed on tumors. In this article, we attempt to illustrate the broad utility of SPIO in molecular imaging, including some of the recent developments, such as the transformation of SPIO into an activatable probe termed the magnetic relaxation switch.
735 citations
TL;DR: A number of techniques are currently being used to create nanoscale topographies for cell scaffolding, which fall into two main categories: techniques that create ordered topographies and those that create unordered topographies.
Abstract: Observations of how controlling the microenvironment of cell cultures can lead to changes in a variety of parameters has lead investigators to begin studying how the nanoenvironment of a culture can affects cells. Cells have many structures at the nanoscale such as filipodia and cytoskeletal and membrane proteins that interact with the environment surrounding them. By using techniques that can control the nanoenvironment presented to a cell, investigators are beginning to be able to mimic the nanoscale topographical features presented to cells by extracellular matrix proteins such as collagen, which has precise and repeating nanotopography. The belief is that these nanoscale surface features are important to creating more natural cell growth and function. A number of techniques are currently being used to create nanoscale topographies for cell scaffolding. These techniques fall into two main categories: techniques that create ordered topographies and those that create unordered topographies. Electron Beam lithography and photolithograpghy are two standard techniques for creating ordered features. Polymer demixing, phase separation, colloidal lithography and chemical etching are most typically used for creating unordered surface patterns. This review will give an overview of these techniques and cite observations from experiments carried out using them.
367 citations
TL;DR: The results presented here indicate that the use of SL and photocross linkable biomaterials, such as photocrosslinkable PEG, appears feasible for fabricating complex bioactive scaffolds with living cells for a variety of important tissue engineering applications.
Abstract: Stereolithography (SL) was used to fabricate complex 3-D poly(ethylene glycol) (PEG) hydrogels. Photopolymerization experiments were performed to characterize the solutions for use in SL, where the crosslinked depth (or hydrogel thickness) was measured at different laser energies and photoinitiator (PI) concentrations for two concentrations of PEG-dimethacrylate in solution (20% and 30% (w/v)). Hydrogel thickness was a strong function of PEG concentration, PI type and concentration, and energy dosage, and these results were utilized to successfully fabricate complex hydrogel structures using SL, including structures with internal channels of various orientations and multi-material structures. Additionally, human dermal fibroblasts were encapsulated in bioactive PEG photocrosslinked in SL. Cell viability was at least 87% at 2 and 24 h following fabrication. The results presented here indicate that the use of SL and photocrosslinkable biomaterials, such as photocrosslinkable PEG, appears feasible for fabricating complex bioactive scaffolds with living cells for a variety of important tissue engineering applications.
351 citations
TL;DR: Techniques and tools used to study how a cell responds to the physical factors in its environment are reviewed to better elucidate the molecular processes and mechanical forces that dominate the interactions between cells and their physical scaffolds.
Abstract: In the pursuit to understand the interaction between cells and their underlying substrates, the life sciences are beginning to incorporate micro- and nanotechnology-based tools to probe and measure cells. The development of these tools portends endless possibilities for new insights into the fundamental relationships between cells and their surrounding microenvironment that underlie the physiology of human tissue. Here, we review techniques and tools that have been used to study how a cell responds to the physical factors in its environment. We also discuss unanswered questions that could be addressed by these approaches to better elucidate the molecular processes and mechanical forces that dominate the interactions between cells and their physical scaffolds.
339 citations
TL;DR: A model-based markerless motion capture system is presented in this study, which does not require the placement of any markers on the subject's body and is based on visual hull reconstruction and an a priori model of the subject.
Abstract: Human motion capture is frequently used to study musculoskeletal biomechanics and clinical problems, as well as to provide realistic animation for the entertainment industry. The most popular technique for human motion capture uses markers placed on the skin, despite some important drawbacks including the impediment to the motion by the presence of skin markers and relative movement between the skin where the markers are placed and the underlying bone. The latter makes it difficult to estimate the motion of the underlying bone, which is the variable of interest for biomechanical and clinical applications. A model-based markerless motion capture system is presented in this study, which does not require the placement of any markers on the subject's body. The described method is based on visual hull reconstruction and an a priori model of the subject. A custom version of adapted fast simulated annealing has been developed to match the model to the visual hull. The tracking capability and a quantitative validation of the method were evaluated in a virtual environment for a complete gait cycle. The obtained mean errors, for an entire gait cycle, for knee and hip flexion are respectively 1.5 degrees (+/-3.9 degrees ) and 2.0 degrees (+/-3.0 degrees ), while for knee and hip adduction they are respectively 2.0 degrees (+/-2.3 degrees ) and 1.1 degrees (+/-1.7 degrees ). Results for the ankle and shoulder joints are also presented. Experimental results captured in a gait laboratory with a real subject are also shown to demonstrate the effectiveness and potential of the presented method in a clinical environment.
325 citations
TL;DR: Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling.
Abstract: Potential applications of tissue engineering in regenerative medicine range from structural tissues to organs with complex function. This review focuses on the engineering of heart valve tissue, a goal which involves a unique combination of biological, engineering, and technological hurdles. We emphasize basic concepts, approaches and methods, progress made, and remaining challenges. To provide a framework for understanding the enabling scientific principles, we first examine the elements and features of normal heart valve functional structure, biomechanics, development, maturation, remodeling, and response to injury. Following a discussion of the fundamental principles of tissue engineering applicable to heart valves, we examine three approaches to achieving the goal of an engineered tissue heart valve: (1) cell seeding of biodegradable synthetic scaffolds, (2) cell seeding of processed tissue scaffolds, and (3) in-vivo repopulation by circulating endogenous cells of implanted substrates without prior in-vitro cell seeding. Lastly, we analyze challenges to the field and suggest future directions for both preclinical and translational (clinical) studies that will be needed to address key regulatory issues for safety and efficacy of the application of tissue engineering and regenerative approaches to heart valves. Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling.
324 citations
TL;DR: The architecture of health smart home, wearable, and combination systems for the remote monitoring of the mobility of elderly Persons as a mechanism of assessing the health status of elderly persons while in their own living environment is reviewed.
Abstract: Rapid technological advances have prompted the development of a wide range of telemonitoring systems to enable the prevention, early diagnosis and management, of chronic conditions. Remote monitoring can reduce the amount of recurring admissions to hospital, facilitate more efficient clinical visits with objective results, and may reduce the length of a hospital stay for individuals who are living at home. Telemonitoring can also be applied on a long-term basis to elderly persons to detect gradual deterioration in their health status, which may imply a reduction in their ability to live independently. Mobility is a good indicator of health status and thus by monitoring mobility, clinicians may assess the health status of elderly persons. This article reviews the architecture of health smart home, wearable, and combination systems for the remote monitoring of the mobility of elderly persons as a mechanism of assessing the health status of elderly persons while in their own living environment.
297 citations
TL;DR: A novel, robust method to couple finite element models of cardiac mechanics to systems models of the circulation, independent of cardiac phase is presented, encompassing levels from cell to system.
Abstract: In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system.
252 citations
TL;DR: In this article, a finite element model of an ear stored on a computer readable medium having logic representing a three-dimensional geometric model of the ear was presented; logic for meshing individual anatomical structures of ear accounting for whether the anatomical structures include at least one of air, liquid material and solid material.
Abstract: A finite element model of an ear stored on a computer readable medium having logic representing a three-dimensional geometric model of the ear; logic for meshing individual anatomical structures of the ear accounting for whether the anatomical structures include at least one of air, liquid material and solid material; logic for assigning material properties for each anatomical structure based on at least one physical property of each anatomical structure; logic for assigning boundary conditions for some of the anatomical structures indicative of interaction between such anatomical structures; and logic for employing acoustic-structural coupled analysis to the anatomical structures of the ear to generate data indicative of the acoustic effect on mechanical vibration transmission in the ear. Various embodiments of 'one-chamber' and 'two-chamber' analyses and models are described.
248 citations
TL;DR: An approach that reduces several difficulties related to the determination of induced transmembrane voltage (ITV) on irregularly shaped cells is presented, and how the finite-thickness, nonzero-conductivity membrane can be replaced by a boundary condition in which a specific surface conductivity is assigned to the interface between the cell interior and the exterior.
Abstract: The paper presents an approach that reduces several difficulties related to the determination of induced transmembrane voltage (ITV) on irregularly shaped cells. We first describe a method for constructing realistic models of irregularly shaped cells based on microscopic imaging. This provides a possibility to determine the ITV on the same cells on which an experiment is carried out, and can be of considerable importance in understanding and interpretation of the data. We also show how the finite-thickness, nonzero-conductivity membrane can be replaced by a boundary condition in which a specific surface conductivity is assigned to the interface between the cell interior (the cytoplasm) and the exterior. We verify the results obtained using this method by a comparison with the analytical solution for an isolated spherical cell and a tilted oblate spheroidal cell, obtaining a very good agreement in both cases. In addition, we compare the ITV computed for a model of two irregularly shaped CHO cells with the ITV measured on the same two cells by means of a potentiometric fluorescent dye, and also with the ITV computed for a simplified model of these two cells.
209 citations
TL;DR: A four-parameter statistical model for the noninvasive estimation of patient-specific AAA wall strength distribution has been successfully developed, and may provide a more accurate means to estimate patient- specific rupture potential of AAA.
Abstract: The spatial distributions of both wall stress and wall strength are required to accurately evaluate the rupture potential for an individual abdominal aortic aneurysm (AAA). The purpose of this study was to develop a statistical model to non-invasively estimate the distribution of AAA wall strength. Seven parameters–namely age, gender, family history of AAA, smoking status, AAA size, local diameter, and local intraluminal thrombus (ILT) thickness–were either directly measured or recorded from the patients hospital chart. Wall strength values corresponding to these predictor variables were calculated from the tensile testing of surgically procured AAA wall specimens. Backwards–stepwise regression techniques were used to identify and eliminate insignificant predictors for wall strength. Linear mixed-effects modeling was used to derive a final statistical model for AAA wall strength, from which 95% confidence intervals on the model parameters were formed. The final statistical model for AAA wall strength consisted of the following variables: sex, family history, ILT thickness, and normalized transverse diameter. Demonstrative application of the model revealed a unique, complex wall strength distribution, with strength values ranging from 56 N/cm2 to 133 N/cm2. A four-parameter statistical model for the noninvasive estimation of patient-specific AAA wall strength distribution has been successfully developed. The currently developed model represents a first attempt towards the noninvasive assessment of AAA wall strength. Coupling this model with our stress analysis technique may provide a more accurate means to estimate patient-specific rupture potential of AAA.
TL;DR: The engineering principles for preparing high-quality quantum dots and for conjugating the dots to biomolecular ligands are described and discusses recent advances in using quantum dots for in vivo molecular and cellular imaging.
Abstract: Semiconductor quantum dots are luminescent nanoparticles that are under intensive development for use as a new class of optical imaging contrast agents. Their novel properties such as optical tunability, improved photostability, and multicolor light emission have opened new opportunities for imaging living cells and in vivo animal models at unprecedented sensitivity and spatial resolution. Combined with biomolecular engineering strategies for tailoring the particle surfaces at the molecular level, bioconjugated quantum dot probes are well suited for imaging single-molecule dynamics in living cells, for monitoring protein–protein interactions within specific intracellular locations, and for detecting diseased sites and organs in deep tissue. In this article, we describe the engineering principles for preparing high-quality quantum dots and for conjugating the dots to biomolecular ligands. We also discuss recent advances in using quantum dots for in vivo molecular and cellular imaging.
TL;DR: It is shown that the instrument successfully distinguishes between normal and malignant mouse skin, which will lead to advances in the optical diagnosis of cancer in humans.
Abstract: An advanced hyper-spectral imaging (HSI) system has been developed having obvious applications for cancer detection. This HSI system is based on state-of-the-art liquid crystal tunable filter technology coupled to an endoscope. The goal of this unique HSI technology being developed is to obtain spatially resolved images of the slight differences in luminescent properties of malignant versus non-malignant tissues. In this report, the development of the instrument is discussed and the capability of the instrument is demonstrated by observing mouse carcinomas in-vivo. It is shown that the instrument successfully distinguishes between normal and malignant mouse skin. It is hoped that the results of this study will lead to advances in the optical diagnosis of cancer in humans.
TL;DR: The results of the present work indicated that MVAL tissues exhibit complete strain rate insensitivity at and below physiological strain rates under physiological loading conditions, suggesting that experimental tests utilizing quasi-static strain rates are appropriate for constitutive model development for mitral valve tissues.
Abstract: Characterization of the mechanical properties of the native mitral valve leaflets at physiological strain rates is a critical step in improving our understanding of MV function and providing experimental data for dynamic constitutive models. We explored, for the first time, the effects of strain rate (from quasi-static to physiologic) on the biaxial mechanical properties of the native mitral valve anterior leaflet (MVAL). A novel high-speed biaxial testing device was developed, capable of achieving in vitro strain rates reported for the MVAL (Sacks et al., Ann. Biomed. Eng. 30(10):1280–1290, 2002). Porcine MVAL specimens were loaded to physiological load levels with cycle periods of 15, 1, 0.5, 0.1, and 0.05 s. The resulting loading stress–strain responses were found to be remarkably independent of strain rate. The hysteresis, defined as the fraction of the membrane strain energy between the loading and unloading curves tension-areal stretch curves, was low (∼12%) and did not vary with strain rate. The results of the present work indicated that MVAL tissues exhibit complete strain rate insensitivity at and below physiological strain rates under physiological loading conditions. These novel results suggest that experimental tests utilizing quasi-static strain rates are appropriate for constitutive model development for mitral valve tissues. The mechanisms underlying this quasi-elastic behavior are as yet unknown, but are likely an important functional aspect of native mitral valve tissues and clearly warrant further study.
TL;DR: Results show that circumferential cyclic stretch is a possible mediator for AVL remodeling activity and that the contractile and fibrotic phenotypic expression of valve interstitial cells was enhanced.
Abstract: Normal physiological mechanical forces cause constant tissue renewal in aortic valve leaflets (AVL) while altered mechanical forces incite changes in their structural and biological properties. The current study aims at characterizing the remodeling properties of AVL subjected to cyclic circumferential stretch in a sterile ex vivo bioreactor. The leaflets cultured were stretched at a maximum rate of 300%s−1 corresponding to a 15% strain for 48 h. Collagen, sulfated glycosaminoglycan (sGAG), and elastin contents of the stretched, fresh, and statically incubated leaflets were measured. Cusp morphology and cell phenotype were also examined. AVLs exposed to cyclic stretch showed a significant increase in collagen content (p 0.05). Native aortic valve morphology was well preserved in stretched leaflets. Immunohistochemistry and immunoblotting studies showed an increased expression of α-smooth muscle actin (α-SMA) in stretched leaflets while α-SMA expression was reduced in statically incubated AVLs when compared to the fresh leaflets. To conclude, circumferential cyclic stretch altered the extracellular matrix remodeling activity of valvular cells, and consequently the extracellular matrix composition of the AVLs. Most interestingly, the contractile and fibrotic phenotypic expression of valve interstitial cells was enhanced. These results show that circumferential cyclic stretch is a possible mediator for AVL remodeling activity.
TL;DR: Methods that use dual FRET (fluorescence resonance energy transfer) or single molecular beacons in combination with peptide-based or membrane-permeabilization-based delivery, to image the relative level, localization, and dynamics of RNA in live cells are described.
Abstract: The ability to visualize in real-time the expression level and localization of specific RNAs in living cells can offer tremendous opportunities for biological and disease studies. Here we review the recent development of nanostructured oligonucleotide probes for living cell RNA detection, and discuss the biological and engineering issues and challenges of quantifying gene expression in vivo. In particular, we describe methods that use dual FRET (fluorescence resonance energy transfer) or single molecular beacons in combination with peptide-based or membrane-permeabilization-based delivery, to image the relative level, localization, and dynamics of RNA in live cells. Examples of detecting endogenous mRNAs, as well as imaging their subcellular localization and colocalization are given to illustrate the biological applications, and issues in molecular beacon design, probe delivery, and target accessibility are discussed. The nanostructured probes promise to open new and exciting opportunities in sensitive gene detection for a wide range of biological and medical applications.
TL;DR: The results suggest that freezing does have an effect on stress-strain properties, particularly in the low stress region corresponding to physiological conditions, and indicates the importance of bulk water redistribution as one underlying mechanism.
Abstract: Cryoplasty, a freezing therapy, is being used for the treatment of restenosis in peripheral arteries. In addition, cryo-preserved arteries are increasingly used in vascular grafts. While studies are being performed to establish the efficacy of such treatments, very little is known about the postcryosurgical or postcryo-preservation changes in mechanical properties of the arteries. Few studies have examined the effect of freezing in the absence of cryoprotective agents (CPAs), and the several studies done in the presence of CPAs have given mixed results. To examine this issue further, we froze pig femoral arteries in a controlled rate freezer, using an aluminum probe, both in the presence at (−80°C to 1°C/min) and absence (at −20°C for 2 or 5 mins) of CPA and Fetal bovine serum (FBS). Following freezing, artery samples were subjected to uniaxial tensile testing. The weights of the tissue were measured before and after freezing. Our results suggest that freezing does have an effect on stress-strain properties, particularly in the low stress region corresponding to physiological conditions. The mechanisms of this change in mechanical properties may include the loss of smooth muscle cell viability, damage to extra cellular matrix (ECM), bulk redistribution of water, or changes in alignment caused by ice crystal growth. In the case of samples frozen in the absence of CPA or FBS, the results indicated a drastic reduction in weight of the tissue suggesting the importance of bulk water redistribution as one underlying mechanism. To further examine potential mechanisms, we subjected cryopreserved vessels to the same uniaxial tests. The extent of changes in mechanical properties and bulk water redistribution was greatly attenuated; reinforcing that water movement might play a role in the changes observed with freezing.
TL;DR: A multi-domain subset consisting of 14, both old and new, features was derived using Pudil’s sequential floating forward selection (SFFS) method, and the derived feature set was superior to the comparative sets, and seems rather robust to noisy data.
Abstract: Heart murmurs are often the first signs of pathological changes of the heart valves, and they are usually found during auscultation in the primary health care. Distinguishing a pathological murmur from a physiological murmur is however difficult, why an "intelligent stethoscope" with decision support abilities would be of great value. Phonocardiographic signals were acquired from 36 patients with aortic valve stenosis, mitral insufficiency or physiological murmurs, and the data were analyzed with the aim to find a suitable feature subset for automatic classification of heart murmurs. Techniques such as Shannon energy, wavelets, fractal dimensions and recurrence quantification analysis were used to extract 207 features. 157 of these features have not previously been used in heart murmur classification. A multi-domain subset consisting of 14, both old and new, features was derived using Pudil's sequential floating forward selection (SFFS) method. This subset was compared with several single domain feature sets. Using neural network classification, the selected multi-domain subset gave the best results; 86% correct classifications compared to 68% for the first runner-up. In conclusion, the derived feature set was superior to the comparative sets, and seems rather robust to noisy data.
TL;DR: Good agreement between measured and numerically computed total pressure drops observed up to a flow rate of 250 ml/s is an important step to validate the ability of CFD software to describe flow in a physiologically realistic binasal model.
Abstract: Pressure-flow relationships measured in human plastinated specimen of both nasal cavities and maxillary sinuses were compared to those obtained by numerical airflow simulations in a numerical three-dimensional reconstruction issued from CT scans of the plastinated specimen. For experiments, flow rates up to 1,500 ml/s were tested using three different gases: HeO(2), Air, and SF(6). Numerical inspiratory airflow simulations were performed for flow rates up to 353 ml/s in both the nostrils using a finite-volume-based method under steady-state conditions with CFD software using a laminar model. The good agreement between measured and numerically computed total pressure drops observed up to a flow rate of 250 ml/s is an important step to validate the ability of CFD software to describe flow in a physiologically realistic binasal model. The major total pressure drop was localized in the nasal valve region. Airflow was found to be predominant in the inferior median part of nasal cavities. Two main vortices were observed downstream from the nasal valve and toward the olfactory region. In the future, CFD software will be a useful tool for the clinician by providing a better understanding of the complexity of three-dimensional breathing flow in the nasal cavities allowing more appropriate management of the patient's symptoms.
TL;DR: The application of a meshless method, the Method of Fundamental Solutions (MFS) to ECGI, that does not require meshing is evaluated on data from animal experiments and human studies, and compared to BEM.
Abstract: Potential-based inverse electrocardiography is a method for the noninvasive computation of epicardial potentials from measured body surface electrocardiographic data. From the computed epicardial potentials, epicardial electrograms and isochrones (activation sequences), as well as repolarization patterns can be constructed. We term this noninvasive procedure Electrocardiographic Imaging (ECGI). The method of choice for computing epicardial potentials has been the Boundary Element Method (BEM) which requires meshing the heart and torso surfaces and optimizing the mesh, a very time-consuming operation that requires manual editing. Moreover, it can introduce mesh-related artifacts in the reconstructed epicardial images. Here we introduce the application of a meshless method, the Method of Fundamental Solutions (MFS) to ECGI. This new approach that does not require meshing is evaluated on data from animal experiments and human studies, and compared to BEM. Results demonstrate similar accuracy, with the following advantages: 1. Elimination of meshing and manual mesh optimization processes, thereby enhancing automation and speeding the ECGI procedure. 2. Elimination of mesh-induced artifacts. 3. Elimination of complex singular integrals that must be carefully computed in BEM. 4. Simpler implementation. These properties of MFS enhance the practical application of ECGI as a clinical diagnostic tool.
TL;DR: A strategy that combines parametric and nonparametric techniques is developed and implemented to minimize the false lesion classifications in multiple sclerosis brains and is quantitatively evaluated on 23 MS patients.
Abstract: The presence of large number of false lesion classification on segmented brain MR images is a major problem in the accurate determination of lesion volumes in multiple sclerosis (MS) brains. In order to minimize the false lesion classifications, a strategy that combines parametric and nonparametric techniques is developed and implemented. This approach uses the information from the proton density (PD)- and T2-weighted and fluid attenuation inversion recovery (FLAIR) images. This strategy involves CSF and lesion classification using the Parzen window classifier. Image processing, morphological operations, and ratio maps of PD- and T2-weighted images are used for minimizing false positives. Contextual information is exploited for minimizing the false negative lesion classifications using hidden Markov random field-expectation maximization (HMRF-EM) algorithm. Lesions are delineated using fuzzy connectivity. The performance of this algorithm is quantitatively evaluated on 23 MS patients. Similarity index, percentages of over, under, and correct estimations of lesions are computed by spatially comparing the results of present procedure with expert manual segmentation. The automated processing scheme detected 80% of the manually segmented lesions in the case of low lesion load and 93% of the lesions in those cases with high lesion load.
TL;DR: Results showed that unsteady 3-D simulation and realistic geometry of the upper and large airways up to generations 4–6 can provide a reasonably accurate estimation of lung input impedance.
Abstract: Lung input impedance measured via forced oscillation over low frequency range has been confirmed as sensitive to the degree and the heterogeneity of lung disease. In this study we advanced an image-based, multi-scale computational model for the human lung, which includes upper and central airways, small airways and alveoli tissue unit. A three-dimensional (3-D) realistic model of the upper airway (reconstructed from MRI images) was combined with an anatomically based 3-D model of the central airways (based on MDCT images) to form a 3-D model of the large airways (from mouth to generation 6, incomplete for generations 4–6). The small airway trees distal to the central branches were based on a hypothetical airway tree for a normal healthy lung. A constant phase viscoelastic model was assumed for the alveolar tissue unit. Unsteady airflows in the large airways were simulated based on computational fluid dynamics (CFD). An experimentally measured broadband forcing flow was applied at the mouth. The impedance of the small airways was computed based on a one-dimensional transmission line model. The computed overall dynamic lung resistance and elastance compared very well with experimental values. Results showed that unsteady 3-D simulation and realistic geometry of the upper and large airways up to generations 4–6 can provide a reasonably accurate estimation of lung input impedance. The impedance of the upper airway constitutes a significant part of the total lung input impedance. The resistance of the upper airway accounts for 45–70% of the total lung resistance at frequencies between 0 and 1 Hz, and 70–81% at frequencies between 1 and 8 Hz.
TL;DR: Direct evidence is described of the ability of Schwann cell alignment alone to direct neurite outgrowth in the absence of other directional cues, and a new method for examining neuronal–Schwann cell interactions in vitro is provided.
Abstract: Schwann cells enhance axonal regeneration following nerve injury in vivo and provide a favorable substrate for neurite outgrowth in vitro. However, much remains unknown about the nature of interactions that occur between Schwann cells and growing neurites. In this paper, we describe direct evidence of the ability of Schwann cell alignment alone to direct neurite outgrowth. Previously, we reported that laminin micropatterns can be used to align Schwann cells and thus create oriented Schwann cell monolayers. In the current study, dissociated rat spinal neurons were seeded onto oriented Schwann cell monolayers, whose alignment provided the only directional cue for growing neurites, and neurite alignment with the underlying Schwann cells was analyzed. The orientation of neurite outgrowth mimicked that of the Schwann cells. Associations observed between neurites and Schwann cells suggest that Schwann cells may guide neurite outgrowth through both topographical and molecular mechanisms. This work demonstrates that Schwann cell alignment can direct neurite outgrowth in the absence of other directional cues, and provides a new method for examining neuronal–Schwann cell interactions in vitro.
TL;DR: A novel closed, “one-and-a-half dimensional” model was obtained that would capture certain physical phenomena that have been neglected in the derivation of the standard axially symmetric one-dimensional models, while at the same time keeping the numerical simulations fast and simple.
Abstract: The focus of this work is on modeling blood flow in medium-to-large systemic arteries assuming cylindrical geometry, axially symmetric flow, and viscoelasticity of arterial walls. The aim was to develop a reduced model that would capture certain physical phenomena that have been neglected in the derivation of the standard axially symmetric one-dimensional models, while at the same time keeping the numerical simulations fast and simple, utilizing one-dimensional algorithms. The viscous Navier–Stokes equations were used to describe the flow and the linearly viscoelastic membrane equations to model the mechanical properties of arterial walls. Using asymptotic and homogenization theory, a novel closed, “one-and-a-half dimensional” model was obtained. In contrast with the standard one-dimensional model, the new model captures: (1) the viscous dissipation of the fluid, (2) the viscoelastic nature of the blood flow – vessel wall interaction, (3) the hysteresis loop in the viscoelastic arterial walls dynamics, and (4) two-dimensional flow effects to the leading-order accuracy. A numerical solver based on the 1D-Finite Element Method was developed and the numerical simulations were compared with the ultrasound imaging and Doppler flow loop measurements. Less than 3% of difference in the velocity and less than 1% of difference in the maximum diameter was detected, showing excellent agreement between the model and the experiment.
TL;DR: The primary finding was that while the MVAL leaflet exhibited significant stress relaxation, it exhibited negligible creep over the 3-h test, suggesting that valvular tissues are unequalled in their ability to withstand significant loading without time-dependent material effects.
Abstract: A fundamental assumption in mitral valve (MV) therapies is that a repaired or replaced valve should mimic the functionality of the native valve as closely as possible. Thus, improvements in valvular treatments are dependent on the establishment of a complete understanding of the function and mechanical properties of the native normal MV. In a recent study [Grashow et al. ABME 34(2), 2006] we demonstrated that the planar biaxial stress–strain relationship of the MV anterior leaflet (MVAL) exhibited minimal hysteresis and a stress–strain response independent of strain rate, suggesting that MVAL could be modeled as a “quasi-elastic” material. The objective of our current study was to expand these results to provide a more complete picture of the time-dependent mechanical properties of the MVAL. To accomplish this, biaxial stress-relaxation and creep studies were performed on porcine MVAL specimens. Our primary finding was that while the MVAL leaflet exhibited significant stress relaxation, it exhibited negligible creep over the 3-h test. These results furthered our assertion that the MVAL functionally behaves not as a linear or non-linear viscoelastic material, but as an anisotropic quasi-elastic material. These results appear to be unique in the soft tissue literature; suggesting that valvular tissues are unequalled in their ability to withstand significant loading without time-dependent material effects. Moreover, insight into these specialized characteristics can help guide and inform efforts directed toward surgical repair and engineered valvular tissue replacements.
TL;DR: The results showed elevated LDL concentration and reduced oxygen concentration in the subendothelial layer of the arterial wall in areas where WSS is low, suggesting that low WSS might be responsible for lipid accumulation and hypoxia in the arterials wall.
Abstract: Mechanical forces, such as low wall shear stress (WSS), are implicated in endothelial dysfunction and atherogenesis. The accumulation of low density lipoprotein (LDL) and hypoxia are also considered as main contributing factors in the development of atherosclerosis. The objective of this study was to investigate the influences of WSS on arterial mass transport by modelling the flow of blood and solute transport in the lumen and arterial wall. The Navier-Stokes equations and Darcy's Law were used to describe the fluid dynamics of the blood in the lumen and wall respectively. Convection-diffusion-reaction equations were used to model LDL and oxygen transport. The coupling of fluid dynamics and solute dynamics at the endothelium was achieved by the Kedem-Katchalsky equations. A shear-dependent hydraulic conductivity relation extracted from experimental data in the literature was employed for the transport of LDL and a shear-dependent permeability was used for oxygen. The integrated fluid-wall model was implemented in Comsol Multiphysics 3.2 and applied to an axisymmetric stenosis. The results showed elevated LDL concentration and reduced oxygen concentration in the subendothelial layer of the arterial wall in areas where WSS is low, suggesting that low WSS might be responsible for lipid accumulation and hypoxia in the arterial wall.
TL;DR: The mechanisms underlying flow-induced cell and collagen alignment suggest that interstitial flow first induces collagen fiber alignment, providing contact guidance for the cells to orient along the aligned matrix; later, the aligned cells further remodel and align their surrounding matrix fibers.
Abstract: Interstitial fluid flow, critical for macromolecular transport, was recently shown to drive fibroblast differentiation and perpendicular cell and matrix alignment in 3D collagen cultures. Here we explore the mechanisms underlying this flow-induced cell and collagen alignment. Cell and matrix alignment was assessed from 3D confocal reflectance stacks using a Fast Fourier Transform method. We found that human dermal and lung fibroblasts align perpendicular to flow in the range of 5-13 mum/s (0.1-0.3 dyn/cm(2)) in collagen; however, neither cells nor matrix fibers align in fibrin cultures, which unlike collagen, is covalently cross-linked and generally degraded by cell fibrinolysis. We also found that even acellular collagen matrices align weakly upon exposure to flow. Matrix alignment begins within 12 h of flow onset and continues, along with cell alignment, over 48 h. Together, these data suggest that interstitial flow first induces collagen fiber alignment, providing contact guidance for the cells to orient along the aligned matrix; later, the aligned cells further remodel and align their surrounding matrix fibers. These findings help elucidate the effects of interstitial flow on cells in matrices and have relevance physiologically in tissue remodeling and in tissue engineering applications.
TL;DR: Arguments are provided that the reduction factor of the CPU requirements from bidomain to monodomain computations, using order-optimal methods, typically is about 10 for simple cell models and less than two for more complex cell models.
Abstract: The bidomain model, coupled with accurate models of cell membrane kinetics, is generally believed to provide a reasonable basis for numerical simulations of cardiac electrophysiology. Because of changes occurring in very short time intervals and over small spatial domains, discretized versions of these models must be solved on fine computational grids, and small time-steps must be applied. This leads to huge computational challenges that have been addressed by several authors. One popular way of reducing the CPU demands is to approximate the bidomain model by the monodomain model, and thus reducing a two by two set of partial differential equations to one scalar partial differential equation; both of which are coupled to a set of ordinary differential equations modeling the cell membrane kinetics. A reduction in CPU time of two orders of magnitude has been reported. It is the purpose of the present paper to provide arguments that such a reduction is not present when order-optimal numerical methods are applied. Theoretical considerations and numerical experiments indicate that the reduction factor of the CPU requirements from bidomain to monodomain computations, using order-optimal methods, typically is about 10 for simple cell models and less than two for more complex cell models.
TL;DR: It is suggested that a range of magnitudes should be examined for each application of whole-body vibration, as increasing magnitudes of WBV were associated with a non-dose-dependent increase in trabecular bone volume at the proximal tibial metaphysis, although other sites were unresponsive.
Abstract: It has been reported that whole-body vibration (WBV) is anabolic to trabecular bone in animal models and humans. It is likely that this anabolic response does not occur uniformly throughout the entire body. Two factors that may affect the observed anabolic response are vibration magnitude and skeletal site of interest. In this study, mice were loaded with WBV of varying magnitudes. After five weeks of loading, bone marrow was flushed from tibias in order to quantify osteoprogenitor cells. Staining with alizarin red (an indicator of mineralization) showed a significant decrease in percent stained area in the 0.3 g loaded group compared to the control group and the 1.0 g group. MicroCT analysis was performed at five skeletal sites: the proximal tibial metaphysis, femoral condyles, distal femoral metaphysis, proximal femur, and L5 vertebral body. Increasing magnitudes of WBV were associated with a non-dose-dependent increase in trabecular bone volume (BV/TV) at the proximal tibial metaphysis, although other sites were unresponsive. There were statistically significant increases in BV/TV in the 0.1 g group (32% increase) and 1.0 g group (43% increase) compared to control (p < 0.05). The 0.1 g and 1.0 g groups also had higher BV/TV than the 0.3 g loaded group. If this non-dose-dependent phenomenon is verified by future studies, it suggests that a range of magnitudes should be examined for each application of WBV.
TL;DR: The history and major design constraints of LQMCSs, the basic principles of human thermoregulation underneath protective clothing, and potential areas of research into tubing/fabric technology, coolant distribution, and control optimization that may enhance the efficiency of L qmCSs are reviewed.
Abstract: The use of protective clothing, whether in space suits, hazardous waste disposal, or sporting equipment, generally increases the risk of heat stress and hyperthermia by impairing the capacity for evaporative heat exchange from the body to the environment. To date the most efficient method of microclimate cooling underneath protective clothing has been via conductive heat exchange from circulating cooling fluid next to the skin. In order to make the use of liquid microclimate cooling systems ((LQ)MCSs) as portable and practical as possible, the physiological and biomedical engineering design goals should be towards maximizing the efficiency of cooling to maintain thermal comfort/neutrality with the least cooling possible to minimize coolant and power requirements. Meeting these conditions is an extremely complex task that requires designing for a plethora of different factors. The optimal fitting of the (LQ)MCSs, along with placement and design of tubing and control of cooling, appear to be key avenues towards maximizing efficiency of heat exchange. We review the history and major design constraints of (LQ)MCSs, the basic principles of human thermoregulation underneath protective clothing, and explore potential areas of research into tubing/fabric technology, coolant distribution, and control optimization that may enhance the efficiency of (LQ)MCSs.