Publications by authors named "Seungik Baek"

27 Publications

  • Page 1 of 1

Inverse modeling framework for characterizing patient-specific microstructural changes in the pulmonary arteries.

J Mech Behav Biomed Mater 2021 Mar 27;119:104448. Epub 2021 Mar 27.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA.

Microstructural changes in the pulmonary arteries associated with pulmonary arterial hypertension (PAH) is not well understood and characterized in humans. To address this issue, we developed and applied a patient-specific inverse finite element (FE) modeling framework to characterize mechanical and structural changes of the micro-constituents in the proximal pulmonary arteries using in-vivo pressure measurements and magnetic resonance images. The framework was applied using data acquired from a pediatric PAH patient and a heart transplant patient with normal pulmonary arterial pressure, which serves as control. Parameters of a constrained mixture model that are associated with the structure and mechanical properties of elastin, collagen fibers and smooth muscle cells were optimized to fit the patient-specific pressure-diameter responses of the main pulmonary artery. Based on the optimized parameters, individual stress and linearized stiffness resultants of the three tissue constituents, as well as their aggregated values, were estimated in the pulmonary artery. Aggregated stress resultant and stiffness are, respectively, 4.6 and 3.4 times higher in the PAH patient than the control subject. Stress and stiffness resultants of each tissue constituent are also higher in the PAH patient. Specifically, the mean stress resultant is highest in elastin (PAH: 69.96, control: 14.42 kPa-mm), followed by those in smooth muscle cell (PAH: 13.95, control: 4.016 kPa-mm) and collagen fibers (PAH: 13.19, control: 2.908 kPa-mm) in both the PAH patient and the control subject. This result implies that elastin may be the key load-bearing constituent in the pulmonary arteries of the PAH patient and the control subject.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104448DOI Listing
March 2021

Patient-Specific Computational Analysis of Hemodynamics and Wall Mechanics and Their Interactions in Pulmonary Arterial Hypertension.

Front Bioeng Biotechnol 2020 28;8:611149. Epub 2021 Jan 28.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.

Vascular wall stiffness and hemodynamic parameters are potential biomechanical markers for detecting pulmonary arterial hypertension (PAH). Previous computational analyses, however, have not considered the interaction between blood flow and wall deformation. Here, we applied an established computational framework that utilizes patient-specific measurements of hemodynamics and wall deformation to analyze the coupled fluid-vessel wall interaction in the proximal pulmonary arteries (PA) of six PAH patients and five control subjects. Specifically, we quantified the linearized stiffness (), relative area change (RAC), diastolic diameter (), regurgitant flow, and time-averaged wall shear stress (TAWSS) of the proximal PA, as well as the total arterial resistance ( ) and compliance ( ) at the distal pulmonary vasculature. Results found that the average proximal PA was stiffer [median: 297 kPa, interquartile range (IQR): 202 kPa vs. median: 75 kPa, IQR: 5 kPa; = 0.007] with a larger diameter (median: 32 mm, IQR: 5.25 mm vs. median: 25 mm, IQR: 2 mm; = 0.015) and a reduced RAC (median: 0.22, IQR: 0.10 vs. median: 0.42, IQR: 0.04; = 0.004) in PAH compared to our control group. Also, higher total resistance ( ; median: 6.89 mmHg × min/l, IQR: 2.16 mmHg × min/l vs. median: 3.99 mmHg × min/l, IQR: 1.15 mmHg × min/l; = 0.002) and lower total compliance ( ; median: 0.13 ml/mmHg, IQR: 0.15 ml/mmHg vs. median: 0.85 ml/mmHg, IQR: 0.51 ml/mmHg; = 0.041) were observed in the PAH group. Furthermore, lower TAWSS values were seen at the main PA arteries (MPAs) of PAH patients (median: 0.81 Pa, IQR: 0.47 Pa vs. median: 1.56 Pa, IQR: 0.89 Pa; = 0.026) compared to controls. Correlation analysis within the PAH group found that was directly correlated to the PA regurgitant flow ( = 0.84, = 0.018) and inversely related to TAWSS ( = -0.72, = 0.051). Results suggest that the estimated elastic modulus may be closely related to PAH hemodynamic changes in pulmonary arteries.
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http://dx.doi.org/10.3389/fbioe.2020.611149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901991PMC
January 2021

Intraluminal thrombus effect on the progression of abdominal aortic aneurysms by using a multistate continuous-time Markov chain model.

J Int Med Res 2020 Nov;48(11):300060520968449

Department of Statistics, Seoul National University, Seoul, Republic of Korea.

Objective: To investigate the relationship between the characteristics of intraluminal thrombus (ILT) with abdominal aortic aneurysm (AAA) expansion.

Methods: This retrospective clinical study applied homogeneous multistate continuous-time Markov chain models to longitudinal computed tomography (CT) data from Korean patients with AAA. Four AAA states were considered (early, mild, severe, fatal) and the maximal thickness of the ILT (max), the fraction of the wall area covered by the ILT (area) and the fraction of ILT volume (vol) were used as covariates.

Results: The analysis reviewed longitudinal CT images from 26 patients. Based on likelihood-ratio statistics, the area was the most significant biomarker and max was the second most significant. In addition, within AAAs that developed an ILT layer, the analysis found that the AAA expands relatively quickly during the early stage but the rate of expansion reduces once the AAA has reached a larger size.

Conclusion: The results recommend surgical intervention when a patient has an area more than 60%. Although this recommendation should be considered with caution given the limited sample size, physicians can use the proposed model as a tool to find such recommendations with their own data.
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http://dx.doi.org/10.1177/0300060520968449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673060PMC
November 2020

Potential damage in pulmonary arterial hypertension: An experimental study of pressure-induced damage of pulmonary artery.

J Biomed Mater Res A 2021 May 3;109(5):579-589. Epub 2020 Aug 3.

Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.

Pulmonary arterial hypertension (PAH) is associated with elevated pulmonary arterial pressure. PAH prognosis remains poor with a 15% mortality rate within 1 year, even with modern clinical management. Previous clinical studies proposed wall shear stress (WSS) to be an important hemodynamic factor affecting cell mechanotransduction, growth and remodeling, and disease progress in PAH. However, WSS in vivo is typically at most 2.5 Pa and a doubt has been cast whether WSS alone can drive disease progress. Furthermore, our current understanding of PAH pathology largely comes from small animals' studies in which caliber enlargement, a hallmark of PAH in humans, is rarely reported. Therefore, a large-animal experiment on pulmonary arteries (PAs) is needed to validate whether increased pressure can induce enlargement of PAs caliber. In this study, we use an inflation testing device to characterize the mechanical behavior, both nonlinear elastic behavior and irreversible damage of porcine arteries. The parameters of elastic behavior are estimated from the inflation test at a low-pressure range before and after over-pressurization. Then, histological images are qualitatively examined for medial and adventitial layers. This study sheds light on the relevance of pressure-induced damage mechanism in human PAH.
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http://dx.doi.org/10.1002/jbm.a.37042DOI Listing
May 2021

Multiscale Modeling Framework of Ventricular-Arterial Bi-directional Interactions in the Cardiopulmonary Circulation.

Front Physiol 2020 31;11. Epub 2020 Jan 31.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.

Ventricular-arterial coupling plays a key role in the physiologic function of the cardiovascular system. We have previously described a hybrid lumped-finite element (FE) modeling framework of the systemic circulation that couples idealized FE models of the aorta and the left ventricle (LV). Here, we describe an extension of the lumped-FE modeling framework that couples patient-specific FE models of the left and right ventricles, aorta and the large pulmonary arteries in both the systemic and pulmonary circulations. Geometries of the FE models were reconstructed from magnetic resonance (MR) images acquired in a pediatric patient diagnosed with pulmonary arterial hypertension (PAH). The modeling framework was calibrated with pressure waveforms acquired in the heart and arteries by catheterization as well as ventricular volume and arterial diameter waveforms measured from MR images. The calibrated model hemodynamic results match well with the clinically-measured waveforms (volume and pressure) in the LV and right ventricle (RV) as well as with the clinically-measured waveforms (pressure and diameter) in the aorta and main pulmonary artery. The calibrated framework was then used to simulate three cases, namely, (1) an increase in collagen in the large pulmonary arteries, (2) a decrease in RV contractility, and (3) an increase in the total pulmonary arterial resistance, all characteristics of progressive PAH. The key finding from these simulations is that hemodynamics of the pulmonary vasculature and RV wall stress are more sensitive to vasoconstriction with a 10% of reduction in the lumen diameter of the distal vessels than a 67% increase in the proximal vessel's collagen mass.
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http://dx.doi.org/10.3389/fphys.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025512PMC
January 2020

Predicting abdominal aortic aneurysm growth using patient-oriented growth models with two-step Bayesian inference.

Comput Biol Med 2020 02 13;117:103620. Epub 2020 Jan 13.

Department of Mechanical Engineering, Michigan State University, 2457 Engineering Building, East Lansing, MI, 48824, USA. Electronic address:

Objective: For small abdominal aortic aneurysms (AAAs), a regular follow-up examination is recommended every 12 months for AAAs of 30-39 mm and every six months for AAAs of 40-55 mm. Follow-up diameters can determine if a patient follows the common growth model of the population. However, the rapid expansion of an AAA, often associated with higher rupture risk, may be overlooked even though it requires surgical intervention. Therefore, the prognosis of abdominal aortic aneurysm growth is clinically important for planning treatment. This study aims to build enhanced Bayesian inference methods to predict maximum aneurysm diameter.

Methods: 106 CT scans from 25 Korean AAA patients were retrospectively obtained. A two-step approach based on Bayesian calibration was used, and an exponential abdominal aortic aneurysm growth model (population-based) was specified according to each individual patient's growth (patient-specific) and morphologic characteristics of the aneurysm sac (enhanced). The distribution estimates were obtained using a Markov Chain Monte Carlo (MCMC) sampler.

Results: The follow-up diameters were predicted satisfactorily (i.e. the true follow-up diameter was in the 95% prediction interval) for 79% of the scans using the population-based growth model, and 83% of the scans using the patient-specific growth model. Among the evaluated geometric measurements, centerline tortuosity was a significant (p = 0.0002) predictor of growth for AAAs with accelerated and stable expansion rates. Using the enhanced prediction model, 86% of follow-up scans were predicted satisfactorily. The average prediction errors of population-based, patient-specific, and enhanced models were ±2.67, ±2.61 and ± 2.79 mm, respectively.

Conclusion: A computational framework using patient-oriented growth models provides useful tools for per-patient basis treatment and enables better prediction of AAA growth.
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http://dx.doi.org/10.1016/j.compbiomed.2020.103620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064358PMC
February 2020

Utilization of the Theory of Small on Large Deformation for Studying Mechanosensitive Cellular Behaviors.

J Elast 2019 Aug 25;136(2):137-157. Epub 2018 Sep 25.

Department of Chemical Engineering, Michigan State University, East Lansing, MI 48824, US.

Recent studies suggest that cells routinely probe their mechanical environments and that this mechanosensitive behavior regulates some of their cellular activities. The finite elasticity theory of small-on-large deformation (SoL) has been shown to be effective in interpreting the mechanosensitive behavior of cells on a substrate that has been subjected to a prior large static stretch before the culturing of the cells. Small on large deformation is the superposition of a small deformation onto a prior large deformation that serves as the new reference configuration. This article aims to refine SoL theory to develop a theoretical framework for improved physical interpretation of mechanosensing. Given the initial large deformation in SoL, the stress generated by the small deformation is linearized, and the linearized elasticity tensor is taken to be a significant factor facilitating prediction of cellular behavior. The pre-stretch is shown to produce direction-based, effective elastic moduli for cellular mechanosensing. The utility of this SoL theory is illustrated by culturing of two different cell types grown on uniaxially pre-stretched surfaces that induce changes to the cell orientation and behavior.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785204PMC
August 2019

Patient-Specific Prediction of Abdominal Aortic Aneurysm Expansion Using Bayesian Calibration.

IEEE J Biomed Health Inform 2019 11 30;23(6):2537-2550. Epub 2019 Jan 30.

Translating recent advances in abdominal aortic aneurysm (AAA) growth and remodeling (G&R) knowledge into a predictive, patient-specific clinical treatment tool requires a major paradigm shift in computational modeling. The objectives of this study are to develop a prediction framework that first calibrates the physical AAA G&R model using patient-specific serial computed tomography (CT) scan images, predicts the expansion of an AAA in the future, and quantifies the associated uncertainty in the prediction. We adopt a Bayesian calibration method to calibrate parameters in the G&R computational model and predict the magnitude of AAA expansion. The proposed Bayesian approach can take different sources of uncertainty; therefore, it is well suited to achieve our aims in predicting the AAA expansion process as well as in computing the propagated uncertainty. We demonstrate how to achieve the proposed aims by solving the formulated Bayesian calibration problems for cases with the synthetic G&R model output data and real medical patient-specific CT data. We compare and discuss the performance of predictions and computation time under different sampling cases of the model output data and patient data, both of which are simulated by the G&R computation. Furthermore, we apply our Bayesian calibration to real patient-specific serial CT data and validate our prediction. The accuracy and efficiency of the proposed method is promising, which appeals to computational and medical communities.
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http://dx.doi.org/10.1109/JBHI.2019.2896034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890695PMC
November 2019

Prediction of Abdominal Aortic Aneurysm Growth Using Dynamical Gaussian Process Implicit Surface.

IEEE Trans Biomed Eng 2019 03 2;66(3):609-622. Epub 2018 Jul 2.

Objective: We propose a novel approach to predict the Abdominal Aortic Aneurysm (AAA) growth in future time, using longitudinal computer tomography (CT) scans of AAAs that are captured at different times in a patient-specific way.

Methods: We adopt a formulation that considers a surface of the AAA as a manifold embedded in a scalar field over the three dimensional (3D) space. For this formulation, we develop our Dynamical Gaussian Process Implicit Surface (DGPIS) model based on observed surfaces of 3D AAAs as visible variables while the scalar fields are hidden. In particular, we use Gaussian process regression to construct the field as an observation model from CT training image data. We then learn a dynamic model to represent the evolution of the field. Finally, we derive the predicted AAA surface from the predicted field along with uncertainty quantified in future time.

Results: A dataset of 7 subjects (4-7 scans) was collected and used to evaluate the proposed method by comparing its prediction Hausdorff distance errors against those of simple extrapolation. In addition, we evaluate the prediction results with respect to a conventional shape analysis technique such as Principal Component Analysis (PCA). All comparative results show the superior prediction performance of the proposed approach.

Conclusion: We introduce a novel approach to predict the AAA growth and its predicted uncertainty in future time, using longitudinal CT scans in a patient-specific fashion.

Significance: The capability to predict the AAA shape and its confidence region by our approach establish the potential for guiding clinicians with informed decision in conducting medical treatment and monitoring of AAAs.
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http://dx.doi.org/10.1109/TBME.2018.2852306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414317PMC
March 2019

High Spatial Resolution Multi-Organ Finite Element Modeling of Ventricular-Arterial Coupling.

Front Physiol 2018 2;9:119. Epub 2018 Mar 2.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.

While it has long been recognized that bi-directional interaction between the heart and the vasculature plays a critical role in the proper functioning of the cardiovascular system, a comprehensive study of this interaction has largely been hampered by a lack of modeling framework capable of simultaneously accommodating high-resolution models of the heart and vasculature. Here, we address this issue and present a computational modeling framework that couples finite element (FE) models of the left ventricle (LV) and aorta to elucidate ventricular-arterial coupling in the systemic circulation. We show in a baseline simulation that the framework predictions of (1) LV pressure-volume loop, (2) aorta pressure-diameter relationship, (3) pressure-waveforms of the aorta, LV, and left atrium (LA) over the cardiac cycle are consistent with the physiological measurements found in healthy human. To develop insights of ventricular-arterial interactions, the framework was then used to simulate how alterations in the geometrical or, material parameter(s) of the aorta affect the LV and vice versa. We show that changing the geometry and microstructure of the aorta model in the framework led to changes in the functional behaviors of both LV and aorta that are consistent with experimental observations. On the other hand, changing contractility and passive stiffness of the LV model in the framework also produced changes in both the LV and aorta functional behaviors that are consistent with physiology principles.
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http://dx.doi.org/10.3389/fphys.2018.00119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841309PMC
March 2018

Image-based computational assessment of vascular wall mechanics and hemodynamics in pulmonary arterial hypertension patients.

J Biomech 2018 02 27;68:84-92. Epub 2017 Dec 27.

Department of Mechanical Engineering, Michigan State University, 2555 Engineering Building, East Lansing, MI 48824, USA. Electronic address:

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevated pulmonary arterial (PA) pressure. While several computational hemodynamic models of the pulmonary vasculature have been developed to understand PAH, they are lacking in some aspects, such as the vessel wall deformation and its lack of calibration against measurements in humans. Here, we describe a computational modeling framework that addresses these limitations. Specifically, computational models describing the coupling of hemodynamics and vessel wall mechanics in the pulmonary vasculature of a PAH patient and a normal subject were developed. Model parameters, consisting of linearized stiffness E of the large vessels and Windkessel parameters for each outflow branch, were calibrated against in vivo measurements of pressure, flow and vessel wall deformation obtained, respectively, from right-heart catheterization, phase-contrast and cine magnetic resonance images. Calibrated stiffness E of the proximal PA was 2.0 and 0.5 MPa for the PAH and normal models, respectively. Calibrated total compliance C and resistance R of the distal vessels were, respectively, 0.32 ml/mmHg and 11.3 mmHg∗min/l for the PAH model, and 2.93 ml/mmHg and 2.6 mmHg∗min/l for the normal model. These results were consistent with previous findings that the pulmonary vasculature is stiffer with more constricted distal vessels in PAH patients. Individual effects on PA pressure due to remodeling of the distal and proximal compartments of the pulmonary vasculature were also investigated in a sensitivity analysis. The analysis suggests that the remodeling of distal vasculature contributes more to the increase in PA pressure than the remodeling of proximal vasculature.
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http://dx.doi.org/10.1016/j.jbiomech.2017.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783768PMC
February 2018

A Potential Tool for the Study of Venous Ulcers: Blood Flow Responses to Load.

J Biomech Eng 2018 03;140(3)

Fellow ASME Chair of the Dynamics, Design and Rehabilitation (DDR) Committee, Bioengineering Technical Division, Department of Mechanical Engineering, Michigan State University, 2555 Engineering Building, East Lansing, MI 48824-1226 e-mail: .

Venous ulcers are deep wounds that are located predominantly on the lower leg. They are prone to infection and once healed have a high probability of recurrence. Currently, there are no effective measures to predict and prevent venous ulcers from formation. Hence, the goal of this work was to develop a Windkessel-based model that can be used to identify hemodynamic parameters that change between healthy individuals and those with wounds. Once identified, these parameters have the potential to be used as indicators of when internal conditions change, putting the patient at higher risk for wound formation. In order to achieve this goal, blood flow responses in lower legs were measured experimentally by a laser Doppler perfusion monitor (LDPM) and simulated with a modeling approach. A circuit model was developed on the basis of the Windkessel theory. The hemodynamic parameters were extracted for three groups: legs with ulcers ("wounded"), legs without ulcers but from ulcer patients ("nonwounded"), and legs without vascular disease ("healthy"). The model was executed by two independent operators, and both operators reported significant differences between wounded and healthy legs in localized vascular resistance and compliance. The model successfully replicated the experimental blood flow profile. The global and local vascular resistances and compliance parameters rendered quantifiable differences between a population with venous ulcers and healthy individuals. This work supports that the Windkessel modeling approach has the potential to determine patient specific parameters that can be used to identify when conditions change making venous ulcer formation more likely.
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http://dx.doi.org/10.1115/1.4038742DOI Listing
March 2018

Computational fluid dynamic simulation of human carotid artery bifurcation based on anatomy and volumetric blood flow rate measured with magnetic resonance imaging.

Int J Adv Eng Sci Appl Math 2016 Mar 2;8(1):40-60. Epub 2016 Feb 2.

Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.

Blood flow patterns and local hemodynamic parameters have been widely associated with the onset and progression of atherosclerosis in the carotid artery. Assessment of these parameters can be performed noninvasively using cine phase-contrast (PC) magnetic resonance imaging (MRI). In addition, in the last two decades, computational fluid dynamics (CFD) simulation in three dimensional models derived from anatomic medical images has been employed to investigate the blood flow in the carotid artery. This study developed a workflow of a subject-specific CFD analysis using MRI to enhance estimating hemodynamics of the carotid artery. Time-of-flight (TOF) MRI scans were used to construct three-dimensional computational models. PC-MRI measurements were utilized to impose the boundary condition at the inlet and a 0-dimensional lumped parameter model was employed for the outflow boundary condition. The choice of different viscosity models of blood flow as a source of uncertainty was studied, by means of the axial velocity, wall shear stress, and oscillatory shear index. The sequence of workflow in CFD analysis was optimized for a healthy subject using PC-MRI. Then, a patient with carotid artery stenosis and its hemodynamic parameters were examined. The simulations indicated that the lumped parameter model used at the outlet gives physiologically reasonable values of hemodynamic parameters. Moreover, the dependence of hemodynamics parameters on the viscosity models was observed to vary for different geometries. Other factors, however, may be required for a more accurate CFD analysis, such as the segmentation and smoothness of the geometrical model, mechanical properties of the artery's wall, and the prescribed velocity profile at the inlet.
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http://dx.doi.org/10.1007/s12572-016-0161-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987097PMC
March 2016

Interaction of expanding abdominal aortic aneurysm with surrounding tissue: Retrospective CT image studies.

J Nat Sci 2015 Aug;1(8):e150

Department of Radiology, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul, Korea.

Objectives: Abdominal aortic aneurysms (AAA) that rupture have a high mortality rate. Rupture occurs when local mechanical stress exceeds the local mechanical strength of an AAA, so stress profiles such as those from finite element analysis (FEA) are useful. The role and effect of surrounding tissues, like the vertebral column, which have not been extensively studied, are examined in this paper.

Methods: Longitudinal CT scans from ten patients with AAAs were studied to see the effect of surrounding tissues on AAAs. Segmentation was performed to distinguish the AAA from other tissues and we studied how these surrounding tissues affected the shape and curvature of the AAA. Previously established methods by Veldenz et al. were used to split the AAA into 8 sections and examine the specific effects of surrounding tissues on these sections [1]. Three-dimensional models were created to better examine these effects over time. Registration was done in order to compare AAAs longitudinally.

Results: The vertebral column and osteophytes were observed to have been affecting the shape and the curvature of the AAA. Interaction with the spine caused focal flattening in certain areas of the AAA. In 16 of the 41 CT scans, the right posterior dorsal section (section 5), had the highest radius of curvature, which was by far the section that had the maximum radius for a specified CT scan. Evolution of the growing AAA showed increased flattening in this section when comparing the last CT scan to the first scan.

Conclusion: Surrounding tissues have a clear influence on the geometry of an AAA, which may in turn affect the stress profile of AAA. Incorporating these structures in FEA and G&R models will provide a better estimate of stress.

Clinical Relevance: Currently, size is the only variable considered when deciding whether to undergo elective surgery to repair AAA since it is an easy enough measure for clinicians to utilize. However, this may not be the best indicator of rupture risk because small aneurysms also contribute to a high mortality rate. AAA's wall stress is a superior indicator and may be better predicted with the inclusion of these surrounding tissues, which then could be used by clinicians in their decision-making process on whether to operate on an AAA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666317PMC
August 2015

The Impact of Prestretch Induced Surface Anisotropy on Axon Regeneration.

Tissue Eng Part C Methods 2016 02 8;22(2):102-112. Epub 2016 Jan 8.

1 Department of Chemical Engineering and Materials Science, Michigan State University , East Lansing, Michigan.

Nerve regeneration after spinal cord injury requires proper axon alignment to bridge the lesion site and myelination to achieve functional recovery. Significant effort has been invested in developing engineering approaches to induce axon alignment with less focus on myelination. Topological features, such as aligned fibers and channels, have been shown to induce axon alignment, but do not enhance axon thickness. We previously demonstrated that surface anisotropy generated through mechanical prestretch induced mesenchymal stem cells to align in the direction of prestretch. In this study, we demonstrate that static prestretch-induced anisotropy promotes dorsal root ganglion (DRG) neurons to extend thicker axon aggregates along the stretched direction and form aligned fascicular-like axon tracts. Moreover, Schwann cells, when cocultured with DRG neurons on the prestretched surface colocalized with the aligned axons and expressed P0 protein, are indicative of myelination of the aligned axons, thereby demonstrating that prestretch-induced surface anisotropy is beneficial in enhancing axon alignment, growth, and myelination.
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http://dx.doi.org/10.1089/ten.TEC.2015.0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744876PMC
February 2016

Association of Intraluminal Thrombus, Hemodynamic Forces, and Abdominal Aortic Aneurysm Expansion Using Longitudinal CT Images.

Ann Biomed Eng 2016 May 1;44(5):1502-14. Epub 2015 Oct 1.

Department of Mechanical Engineering, Michigan State University, 2555 Engineering Building, East Lansing, MI, 48824, USA.

While hemodynamic forces and intraluminal thrombus (ILT) are believed to play important roles on abdominal aortic aneurysm (AAA), it has been suggested that hemodynamic forces and ILT also interact with each other, making it a complex problem. There is, however, a pressing need to understand relationships among three factors: hemodynamics, ILT accumulation, and AAA expansion for AAA prognosis. Hence this study used longitudinal computer tomography scans from 14 patients and analyzed the relationship between them. Hemodynamic forces, represented by wall shear stress (WSS), were obtained from computational fluid dynamics; ILT accumulation was described by ILT thickness distribution changes between consecutives scans, and ILT accumulation and AAA expansion rates were estimated from changes in ILT and AAA volume. Results showed that, while low WSS was observed at regions where ILT accumulated, the rate at which ILT accumulated occurred at the same rate as the aneurysm expansion. Comparison between AAAs with and without thrombus showed that aneurysm with ILT recorded lower values of WSS and higher values of AAA expansion than those without thrombus. Findings suggest that low WSS may promote ILT accumulation and submit the idea that by increasing WSS levels ILT accumulation may be prevented.
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http://dx.doi.org/10.1007/s10439-015-1461-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826625PMC
May 2016

Prior Distributions of Material Parameters for Bayesian Calibration of Growth and Remodeling Computational Model of Abdominal Aortic Wall.

J Biomech Eng 2015 Oct;137(10):101001

For the accurate prediction of the vascular disease progression, there is a crucial need for developing a systematic tool aimed toward patient-specific modeling. Considering the interpatient variations, a prior distribution of model parameters has a strong influence on computational results for arterial mechanics. One crucial step toward patient-specific computational modeling is to identify parameters of prior distributions that reflect existing knowledge. In this paper, we present a new systematic method to estimate the prior distribution for the parameters of a constrained mixture model using previous biaxial tests of healthy abdominal aortas (AAs). We investigate the correlation between the estimated parameters for each constituent and the patient's age and gender; however, the results indicate that the parameters are correlated with age only. The parameters are classified into two groups: Group-I in which the parameters ce, ck1, ck2, cm2,Ghc, and ϕe are correlated with age, and Group-II in which the parameters cm1, Ghm, G1e, G2e, and α are not correlated with age. For the parameters in Group-I, we used regression associated with age via linear or inverse relations, in which their prior distributions provide conditional distributions with confidence intervals. For Group-II, the parameter estimated values were subjected to multiple transformations and chosen if the transformed data had a better fit to the normal distribution than the original. This information improves the prior distribution of a subject-specific model by specifying parameters that are correlated with age and their transformed distributions. Therefore, this study is a necessary first step in our group's approach toward a Bayesian calibration of an aortic model. The results from this study will be used as the prior information necessary for the initialization of Bayesian calibration of a computational model for future applications.
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http://dx.doi.org/10.1115/1.4031116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574868PMC
October 2015

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine.

J Biomech Eng 2015 Sep;137(9)

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA-spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA-spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients.
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http://dx.doi.org/10.1115/1.4031019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574855PMC
September 2015

Influence of surrounding tissues on biomechanics of aortic wall.

Int J Exp Comput Biomech 2013 Sep;2(2):105-117

Department of Mechanical Engineering, Michigan State University, 2457 Engineering Building, East Lansing, MI 48824-1226, USA.

The present study investigates effects of surrounding tissues and non-uniform wall thickness on the biomechanics of the thoracic aorta. We construct two idealised computational models exemplifying the importance of surrounding tissues and non-uniform wall thickness, namely the uniform-thickness model and the histology image-based model. While the former neglects a connective tissue layer surrounding the aorta, the latter takes it into account with non-uniform wall thickness. Using plane strain finite element analysis, stress distributions in the aortic media between the two models are compared. The histology image-based model substantially enhances the uniformity of stress throughout the aortic media. Furthermore, the altered mechanical properties of surrounding tissues change the stress distribution. These results suggest that surrounding tissues and non-uniform wall thickness should be included in biomechanical analysis to better understand regional adaptation of the aortic wall during normal physiological conditions or pathological conditions such as aortic aneurysms and dissections.
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http://dx.doi.org/10.1504/IJECB.2013.056516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096287PMC
September 2013

Longitudinal differences in the mechanical properties of the thoracic aorta depend on circumferential regions.

J Biomed Mater Res A 2013 May 5;101(5):1525-9. Epub 2012 Nov 5.

Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan 48824, USA.

Understanding the mechanical behavior of the arterial wall and its spatial variations is essential for the study of vascular physiopathology and the design of biomedical devices that interact with the arterial wall. Although it is generally accepted that the aortic wall gets stiffer along its length, the spatial variations in the mechanical behavior of the thoracic aorta are not well understood. In this study, therefore, we investigate both longitudinal and circumferential variations in the mechanical properties of the porcine descending thoracic aorta. Using a previously developed experimental method and stress-strain analysis, the stress, stretch, tangent modulus (TM), and pressure-strain elastic modulus (PSEM) are estimated in the range of in vivo pressure. The results show that the longitudinal differences of both TM and PSEM are statistically significant in the posterior region but not in the anterior region. Both moduli are greater in the posterior distal region when compared with the other test regions. The findings of this study meet a need for clarifying the region investigated, especially in circumferential region, to study the regional variations in biomechanics of blood vessels.
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http://dx.doi.org/10.1002/jbm.a.34445DOI Listing
May 2013

Circumferential variations of mechanical behavior of the porcine thoracic aorta during the inflation test.

J Biomech 2011 Jul 7;44(10):1941-7. Epub 2011 May 7.

Department of Mechanical Engineering, Michigan State University, 2457 Engineering Building, East Lansing, MI 48824-1226, USA.

We developed an extension-inflation experimental apparatus with a stereo vision system and a stress-strain analysis method to determine the regional mechanical properties of a blood vessel. Seven proximal descending thoracic aortas were investigated during the inflation test at a fixed longitudinal stretch ratio of 1.35 over a transmural pressure range from 1.33 to 21.33 kPa. Four circumferential regions of each aorta were designated as the anterior (A), left lateral (L), posterior (P), and right lateral (R) regions, and the inflation test was repeated for each region of the aortas. We used continuous functions to approximate the surfaces of the regional aortic wall in the reference configuration and the deformed configuration. Circumferential stretch and stress at the four circumferential regions of the aorta were computed. Circumferential stiffness, defined as the tangent of the stress-stretch curve, and physiological aortic stiffness, named pressure-strain elastic modulus, were also computed for each region. In the low pressure range, the stress increased linearly with increased stretch, but the mechanical response became progressively stiffer in the high-pressure range above a transition point. At a transmural pressure of 12.00 kPa, mean values of stiffness were 416±104 kPa (A), 523±99 kPa (L), 634±91 kPa (P), and 489±82 kPa (R). The stiffness of the posterior region was significantly higher than that of the anterior region, but no significant difference was found in pressure-strain elastic modulus.
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http://dx.doi.org/10.1016/j.jbiomech.2011.04.022DOI Listing
July 2011

A finite element model of stress-mediated vascular adaptation: application to abdominal aortic aneurysms.

Comput Methods Biomech Biomed Engin 2011 Sep 24;14(9):803-17. Epub 2011 May 24.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI 48824-1224, USA.

Despite rapid expansion of our knowledge of vascular adaptation, developing patient-specific models of diseased arteries is still an open problem. In this study, we extend existing finite element models of stress-mediated growth and remodelling of arteries to incorporate a medical image-based geometry of a healthy aorta and, then, simulate abdominal aortic aneurysm. Degradation of elastin initiates a local dilatation of the aorta while stress-mediated turnover of collagen and smooth muscle compensates the loss of elastin. Stress distributions and expansion rates during the aneurysm growth are studied for multiple spatial distribution functions of elastin degradation and kinetic parameters. Temporal variations of the degradation function are also investigated with either direct time-dependent degradation or stretch-induced degradation as possible biochemical and biomechanical mechanisms for elastin degradation. The results show that this computational model has the capability to capture the complexities of aneurysm progression due to variations of geometry, extent of damage and stress-mediated turnover as a step towards patient-specific modelling.
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http://dx.doi.org/10.1080/10255842.2010.495344DOI Listing
September 2011

Identification of in vivo material and geometric parameters of a human aorta: toward patient-specific modeling of abdominal aortic aneurysm.

Biomech Model Mechanobiol 2011 Oct 6;10(5):689-99. Epub 2010 Nov 6.

Department of Mechanical Engineering, Michigan State University, 2457 Engineering Building, East Lansing, MI 48824-1226, USA.

Recent advances in computational modeling of vascular adaptations and the need for their extension to patient-specific modeling have introduced new challenges to the path toward abdominal aortic aneurysm modeling. First, the fundamental assumption in adaptation models, namely the existence of vascular homeostasis in normal vessels, is not easy to implement in a vessel model built from medical images. Second, subjecting the vessel wall model to the normal pressure often makes the configuration deviate from the original geometry obtained from medical images. To address those technical challenges, in this work, we propose a two-step optimization approach; first, we estimate constitutive parameters of a healthy human aorta intrinsic to the material by using biaxial test data and a weighted nonlinear least-squares parameter estimation method; second, we estimate the distributions of wall thickness and anisotropy using a 2-D parameterization of the vessel wall surface and a global approximation scheme integrated within an optimization routine. A direct search method is implemented to solve the optimization problem. The numerical optimization method results in a considerable improvement in both satisfying homeostatic condition and minimizing the deviation of geometry from the original shape based on in vivo images. Finally, the utility of the proposed technique for patient-specific modeling is demonstrated in a simulation of an abdominal aortic aneurysm enlargement.
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http://dx.doi.org/10.1007/s10237-010-0266-yDOI Listing
October 2011

Blood perfusion and transcutaneous oxygen level characterizations in human skin with changes in normal and shear loads--implications for pressure ulcer formation.

Clin Biomech (Bristol, Avon) 2010 Oct;25(8):823-8

Department of Mechanical Engineering, Michigan State University, East Lansing, MI 48824, USA.

Background: Decubitus ulcers (pressure ulcers) are localized areas of tissue breakdown in the skin and the underlying regions. Decubitus ulcers affect approximately 3 million people in the USA every year, including seniors, individuals with diabetes, and those who spend long periods in wheelchairs. Experimental studies demonstrate that static or dynamic normal loads cause blood occlusion in the skin, while prolonged loading conditions can result in skin damage. However, few studies report the effects of 'normal and shear' combined loading on blood perfusion. The goal of this research was to study alterations of transcutaneous oxygen levels and blood perfusion in human skin when both normal and shear loads were applied.

Methods: Fifteen human subjects were evaluated under seven different conditions for changes in transcutaneous oxygen and blood perfusion levels during applications of normal and shear loading on the forearm. Transcutaneous oxygen levels and blood perfusion were continuously measured using a Laser Doppler system, while applied forces were quantified with a multi-axis load cell.

Findings: Transcutaneous oxygen and blood perfusion levels decreased when shear loads were applied in addition to normal loads. Further, blood perfusion during recovery periods increased gradually from the first to the last test condition.

Interpretation: Results indicate that adding shear loads decreased transcutaneous oxygen and blood perfusion levels in the skin. Based on these findings, shear force may play a role in skin damage, and both shear and normal loads should be considered when trying to prevent ulcer development.
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http://dx.doi.org/10.1016/j.clinbiomech.2010.06.003DOI Listing
October 2010

Cell adhesive behavior on thin polyelectrolyte multilayers: cells attempt to achieve homeostasis of its adhesion energy.

Langmuir 2010 Aug;26(15):12794-802

Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 48824, USA.

Linearly growing ultrathin polyelectrolyte multilayer (PEM) films of strong polyelectrolytes, poly(diallyldimethylammonium chloride) (PDAC), and sulfonated polystyrene, sodium salt (SPS) exhibit a gradual shift from cytophilic to cytophobic behavior, with increasing thickness for films of less than 100 nm. Previous explanations based on film hydration, swelling, and changes in the elastic modulus cannot account for the cytophobicity observed with these thin films as the number of bilayers increases. We implemented a finite element analysis to help elucidate the observed trends in cell spreading. The simulation results suggest that cells maintain a constant level of energy consumption (energy homeostasis) during active probing and thus respond to changes in the film stiffness as the film thickness increases by adjusting their morphology and the number of focal adhesions recruited and thereby their attachment to a substrate.
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http://dx.doi.org/10.1021/la101689zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918384PMC
August 2010

A Computational Framework for Fluid-Solid-Growth Modeling in Cardiovascular Simulations.

Comput Methods Appl Mech Eng 2009 Sep;198(45-46):3583-3602

Department of Bioengineering, Stanford University.

It is now well known that altered hemodynamics can alter the genes that are expressed by diverse vascular cells, which in turn plays a critical role in the ability of a blood vessel to adapt to new biomechanical conditions and governs the natural history of the progression of many types of disease. Fortunately, when taken together, recent advances in molecular and cell biology, in vivo medical imaging, biomechanics, computational mechanics, and computing power provide an unprecedented opportunity to begin to understand such hemodynamic effects on vascular biology, physiology, and pathophysiology. Moreover, with increased understanding will come the promise of improved designs for medical devices and clinical interventions. The goal of this paper, therefore, is to present a new computational framework that brings together recent advances in computational biosolid and biofluid mechanics that can exploit new information on the biology of vascular growth and remodeling as well as in vivo patient-specific medical imaging so as to enable realistic simulations of vascular adaptations, disease progression, and clinical intervention.
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http://dx.doi.org/10.1016/j.cma.2008.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770883PMC
September 2009

On parameter estimation for biaxial mechanical behavior of arteries.

J Biomech 2009 Mar 20;42(4):524-30. Epub 2009 Jan 20.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI 48824-1226, USA.

This article considers the parameter estimation of multi-fiber family models for biaxial mechanical behavior of passive arteries in the presence of the measurement errors. First, the uncertainty propagation due to the errors in variables has been carefully characterized using the constitutive model. Then, the parameter estimation of the artery model has been formulated into nonlinear least squares optimization with an appropriately chosen weight from the uncertainty model. The proposed technique is evaluated using multiple sets of synthesized data with fictitious measurement noises. The results of the estimation are compared with those of the conventional nonlinear least squares optimization without a proper weight factor. The proposed method significantly improves the quality of parameter estimation as the amplitude of the errors in variables becomes larger. We also investigate model selection criteria to decide the optimal number of fiber families in the multi-fiber family model with respect to the experimental data balancing between variance and bias errors.
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http://dx.doi.org/10.1016/j.jbiomech.2008.11.022DOI Listing
March 2009