Magnetizable stent-grafts enable endothelial cell capture.

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Quantitative Computed Tomography Protocols Affect Material Mapping and Quantitative Computed Tomography-Based Finite-Element Analysis Predicted Stiffness.

Quantitative computed tomography-based finite-element analysis (QCT/FEA) has become increasingly popular in an attempt to understand and possibly reduce vertebral fracture risk. It is known that scanning acquisition settings affect Hounsfield units (HU) of the CT voxels. Material properties assignments in QCT/FEA, relating HU to Young's modulus, are performed by applying empirical equations. The purpose of this study was to evaluate the effect of QCT scanning protocols on predicted stiffness values from finite-element models. One fresh frozen cadaveric torso and a QCT calibration phantom were scanned six times varying voltage and current and reconstructed to obtain a total of 12 sets of images. Five vertebrae from the torso were experimentally tested to obtain stiffness values. QCT/FEA models of the five vertebrae were developed for the 12 image data resulting in a total of 60 models. Predicted stiffness was compared to the experimental values. The highest percent difference in stiffness was approximately 480% (80 kVp, 110 mAs, U70), while the lowest outcome was ∼1% (80 kVp, 110 mAs, U30). There was a clear distinction between reconstruction kernels in predicted outcomes, whereas voltage did not present a clear influence on results. The potential of QCT/FEA as an improvement to conventional fracture risk prediction tools is well established. However, it is important to establish research protocols that can lead to results that can be translated to the clinical setting.

The Effect of Quantitative Computed Tomography Acquisition Protocols on Bone Mineral Density Estimation.

Osteoporosis is characterized by bony material loss and decreased bone strength leading to a significant increase in fracture risk. Patient-specific quantitative computed tomography (QCT) finite element (FE) models may be used to predict fracture under physiological loading. Material properties for the FE models used to predict fracture are obtained by converting grayscale values from the CT into volumetric bone mineral density (vBMD) using calibration phantoms. If there are any variations arising from the CT acquisition protocol, vBMD estimation and material property assignment could be affected, thus, affecting fracture risk prediction. We hypothesized that material property assignments may be dependent on scanning and postprocessing settings including voltage, current, and reconstruction kernel, thus potentially having an effect in fracture risk prediction. A rabbit femur and a standard calibration phantom were imaged by QCT using different protocols. Cortical and cancellous regions were segmented, their average Hounsfield unit (HU) values obtained and converted to vBMD. Estimated vBMD for the cortical and cancellous regions were affected by voltage and kernel but not by current. Our study demonstrated that there exists a significant variation in the estimated vBMD values obtained with different scanning acquisitions. In addition, the large noise differences observed utilizing different scanning parameters could have an important negative effect on small subregions containing fewer voxels.

The Computational Fluid Dynamics Rupture Challenge 2013--Phase II: Variability of Hemodynamic Simulations in Two Intracranial Aneurysms.

With the increased availability of computational resources, the past decade has seen a rise in the use of computational fluid dynamics (CFD) for medical applications. There has been an increase in the application of CFD to attempt to predict the rupture of intracranial aneurysms, however, while many hemodynamic parameters can be obtained from these computations, to date, no consistent methodology for the prediction of the rupture has been identified. One particular challenge to CFD is that many factors contribute to its accuracy; the mesh resolution and spatial/temporal discretization can alone contribute to a variation in accuracy. This failure to identify the importance of these factors and identify a methodology for the prediction of ruptures has limited the acceptance of CFD among physicians for rupture prediction. The International CFD Rupture Challenge 2013 seeks to comment on the sensitivity of these various CFD assumptions to predict the rupture by undertaking a comparison of the rupture and blood-flow predictions from a wide range of independent participants utilizing a range of CFD approaches. Twenty-six groups from 15 countries took part in the challenge. Participants were provided with surface models of two intracranial aneurysms and asked to carry out the corresponding hemodynamics simulations, free to choose their own mesh, solver, and temporal discretization. They were requested to submit velocity and pressure predictions along the centerline and on specified planes. The first phase of the challenge, described in a separate paper, was aimed at predicting which of the two aneurysms had previously ruptured and where the rupture site was located. The second phase, described in this paper, aims to assess the variability of the solutions and the sensitivity to the modeling assumptions. Participants were free to choose boundary conditions in the first phase, whereas they were prescribed in the second phase but all other CFD modeling parameters were not prescribed. In order to compare the computational results of one representative group with experimental results, steady-flow measurements using particle image velocimetry (PIV) were carried out in a silicone model of one of the provided aneurysms. Approximately 80% of the participating groups generated similar results. Both velocity and pressure computations were in good agreement with each other for cycle-averaged and peak-systolic predictions. Most apparent "outliers" (results that stand out of the collective) were observed to have underestimated velocity levels compared to the majority of solutions, but nevertheless identified comparable flow structures. In only two cases, the results deviate by over 35% from the mean solution of all the participants. Results of steady CFD simulations of the representative group and PIV experiments were in good agreement. The study demonstrated that while a range of numerical schemes, mesh resolution, and solvers was used, similar flow predictions were observed in the majority of cases. To further validate the computational results, it is suggested that time-dependent measurements should be conducted in the future. However, it is recognized that this study does not include the biological aspects of the aneurysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneurysm.

Effect of mechanical fatigue on commercial bioprosthetic TAVR valve mechanical and microstructural properties.

Valvular structural deterioration is of particular concern for transcatheter aortic valve replacements due to their suspected shorter longevity and increasing use in younger patient populations. In this work we investigated the mechanical and microstructural changes in commercial TAVR valves composed of both glutaraldehyde fixed bovine and porcine pericardium (GLBP and GLPP) following accelerated wear testing (AWT) as outlined in ISO 5840 standards. This provided greater physiological relevance to the loading compared to previous studies and by utilizing digital image correlation we were able to obtain strain contours for each leaflet pre and post fatigue and identify sites of fatigue damage. The areas of greatest change in mechanical strain for each leaflet were then further probed using biaxial tensile testing, confocal microscopy, and electron microscopy. It was observed that overall strain decreased in the GLPP valves following AWT of 200 million cycles while the GLBP valve showed an increase in overall strain. Biaxial tensile testing showed a statistically significant reduction in stress for GLPP while no significant changes were seen for GLBP. Both confocal and electron microscopy showed a disruption to the gross collagen organization and fibrillar structure, including fragmentation, for GLPP but only the former for GLBP. However, further test data is required to confirm these findings and to provide a better understanding of this fatigue pathway is required such that it can be incorporated into both valve design and selection processes to improve overall longevity for both GLPP and GLBP devices.

Magnetic and Biocompatible Polyurethane Nanofiber Biomaterial for Tissue Engineering.

Recruitment of endothelial cells to cardiovascular device surfaces could solve issues of thrombosis, neointimal hyperplasia, and restenosis. Since current targeting strategies are often nonspecific, new technologies to allow for site-specific cell localization and capture in vivo are needed. The development of cytocompatible superparamagnetic iron oxide nanoparticles has allowed for the use of magnetism for cell targeting. In this study, a magnetic polyurethane (PU)-2205 stainless steel (2205-SS) nanofibrous composite biomaterial was developed through analysis of composite sheets and application to stent-grafts. The PU nanofibers provide strength and elasticity while the 2205-SS microparticles provide ferromagnetic properties. Sheets were electrospun at mass ratios of 0-4:1 (2205-SS:PU) and stent-grafts with magnetic or nonmagnetic stents were coated at the optimal ratio of 2:1. These composite materials were characterized by microscopy, mechanical testing, a sessile drop test, magnetic field measurement, magnetic cell capture assays, and cytocompatibility after 14 days of culturing with endothelial cells. Results of this study show that an optimal ratio of 2:1 2205-SS:PU results in a hydrophobic material that balanced mechanical and magnetic properties and was cytocompatible up to 14 days. Significant cell capture required a thicker material of 0.5 mm thickness. Stent-grafts fabricated from a magnetic coating and a magnetic stent demonstrated uniform cell capture throughout the device surface. This novel biomaterial exhibits a combination of mechanical and magnetic properties that enables magnetic capture of cells and other therapeutic agents for vascular and other tissue engineering applications.

Benchtop proof of concept and comparison of iron- and magnesium-based bioresorbable flow diverters.

OBJECTIVE: Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS: BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS: The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS: The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

Bioresorbable flow diverters for the treatment of intracranial aneurysms: review of current literature and future directions.

The use of flow diverters is a rapidly growing endovascular approach for the treatment of intracranial aneurysms. All FDA-approved flow diverters are composed of nitinol or cobalt-chromium, which will remain in the patient for the duration of their life. Bioresorbable flow diverters have been proposed by several independent investigators as the next generation of flow diverting devices. These devices aim to serve their transient function of occluding and healing the aneurysm prior to being safely resorbed by the body, eliminating complications associated with the permanent presence of conventional flow diverters. Theoretical advantages of bioresorbable flow diverters include (1) reduction in device-induced thrombosis; (2) reduction in chronic inflammation and device-induced stenosis; (3) reduction in side branch occlusion; (4) restoration of physiological vasomotor function; (5) reduction in imaging artifacts; and (6) use in pediatric applications. Advances made in the similar bioresorbable coronary stenting field highlight some of these advantages and demonstrate the feasibility and safety of bioresorbable endovascular devices in the clinic. The current work aims to review the progress of bioresorbable flow diverters, identify opportunities for further investigation, and ultimately stimulate the advancement of this technology.

Characterization of Blood Outgrowth Endothelial Cells (BOEC) from Porcine Peripheral Blood.

The endothelium is a dynamic integrated structure that plays an important role in many physiological functions such as angiogenesis, hemostasis, inflammation, and homeostasis. The endothelium also plays an important role in pathophysiologies such as atherosclerosis, hypertension, and diabetes. Endothelial cells form the inner lining of blood and lymphatic vessels and display heterogeneity in structure and function. Various groups have evaluated the functionality of endothelial cells derived from human peripheral blood with a focus on endothelial progenitor cells derived from hematopoietic stem cells or mature blood outgrowth endothelial cells (or endothelial colony-forming cells). These cells provide an autologous resource for therapeutics and disease modeling. Xenogeneic cells may provide an alternative source of therapeutics due to their availability and homogeneity achieved by using genetically similar animals raised in similar conditions. Hence, a robust protocol for the isolation and expansion of highly proliferative blood outgrowth endothelial cells from porcine peripheral blood has been presented. These cells can be used for numerous applications such as cardiovascular tissue engineering, cell therapy, disease modeling, drug screening, studying endothelial cell biology, and in vitro co-cultures to investigate inflammatory and coagulation responses in xenotransplantation.

Finite element analysis in clinical patients with atherosclerosis.

Endovascular plaque composition is strongly related to stent strut stress and is responsible for strut fatigue, stent failure, and possible in-stent restenosis. To evaluate the effect of plaque on artery wall resistance to expansion we performed in silico analysis of atherosclerotic vessels. We generated finite element models from in vivo intravascular ultrasound virtual histology images to determine local artery surface stiffness and determined which plaque structures have the greatest influence. We validated the predictive capacity of our modeling approach by testing an atherosclerotic peripheral artery ex vivo with pressure-inflation testing at physiological pressures ranging from 10 to 200 mmHg. For this purpose, the in silico deformation of the arterial wall was compared to that observed ex vivo. We found that calcification had a positive effect on surface stiffness with fibrous plaque and necrotic core having negative effects. Additionally, larger plaque structures demonstrated significantly higher average surface stiffness and calcification located nearer the lumen was also shown to increase surface stiffness. Therefore, more developed plaques will have greater resistance to expansion and higher stent strut stress, with calcification located near the lumen further increasing stress in localized areas. Thus, it may be expected that such plaque structures may increase the likelihood of localized stent strut fracture.

Improved biocompatibility of Zn-Ag-based stent materials by microstructure refinement.

The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here we investigate the biocompatibility of three Zn-based silver (Ag)-containing alloys, ranging from binary to quinary alloy systems. Selected binary and quinary Zn-Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. This experimental design was intended to clarify the relationship between elemental profile/microstructure and biocompatibility for the Zn-Ag system. We found that the quinary alloy system (Zn-4Ag-0.8Cu-0.6Mn-0.15Zr) performed significantly better, in terms of histomorphometry, than any alloy system we have evaluated to date. Furthermore, when solution treated to increase strength and ductility and reduce the fraction of Ag-rich phases, the quinary alloy's biocompatibility further improved. In vitro corrosion testing and metallographic analysis of in vivo implants demonstrated a more uniform mode of corrosion for the solution treated alloy. We conclude that Zn-Ag alloys can be engineered through alloying to substantially reduce neointimal growth. The positive effect on neointimal growth can be further enhanced by dissolving the AgZn3 precipitates in the Zn matrix to improve the corrosion uniformity. These findings demonstrate that neointimal-forming cells can be regulated by elemental additions and microstructural changes in degradable Zn-based implant materials. STATEMENT OF SIGNIFICANCE: The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here, selected binary and quinary Zn-Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. We found that applying a thermal treatment restores mechanical strength and mitigates the strain rate sensitivity of Zn-Ag alloys by dissolving AgZn3 precipitates. Ag-rich nano-precipitates in Zn decrease biocompatibility, a phenomenon that can be counteracted by dissolving the AgZn3 precipitates in the bulk Zn matrix.

Numerical wave speed sensitivity study for assessment of myocardial elasticity in a simplified linear elastic and isotropic left ventricle model.

Since tissue elasticity can change with pathology, noninvasive assessment of elasticity has received increasing attention. Emerging methods for assessing cardiac elasticity utilize either an external source to induce propagating shear waves or intrinsic longitudinal waves created by natural cardiac events such as left ventricle stretching that occurs due to atrial kick during late diastole. However, the effect of morphological variations that occur in diseased hearts on this longitudinal stretch wave and the corresponding estimate of elasticity is not well understood and is an active area of research. This study investigated the sensitivity of longitudinal wave speed to material properties and chamber geometry parameters through numerical simulations using a finite element model of a bullet-shaped chamber with homogeneous isotropic linear elastic material properties. A longitudinal impulse displacement was applied to the base edge of the model to investigate wave propagation from this boundary. Parametric studies were performed for variables of interest related to geometry and material properties. The wave speeds estimated from simulation results were used to determine wave speed sensitivity to each variable. Wave speed was found to be a strong function of material elasticity and a weak function of chamber geometry and viscous damping. Simulated wave speed as a function of elasticity was in good agreement with wave speeds determined from an analytical expression for longitudinal wave speed in elastic thin plates. These promising preliminary results increase our understanding of how these parameters affect intrinsic longitudinal wave speed and warrant future studies addressing the impact of patient-specific model geometry, material anisotropy and hyperelasticity, and boundary conditions on wave speed.

Finite Element Analysis of the Septal Cartilage L-Strut.

Importance: Septoplasty is one of the most commonly performed operations in the head and neck. However, the reasons for septoplasty failure and the additional stress of performing a chondrotomy on the septal cartilage are not well understood. Design, Setting, and Participants: A finite element model of the nasal septum was created using a microcomputed tomography scan of the nasoseptal complex that was reconstructed into a three-dimensional model in silico. Testing included four common chondrotomy designs: traditional L-strut, double-cornered chondrotomy (DCC), curved L-strut, and the C-curve. Tip displacement was applied in a vector parallel to the caudal strut to simulate nasal tip palpation. Main Outcomes and Measures: With finite element analysis, the maximum principal stress (MPS), von Mises stress (VMS), harvested cartilage volume, and surface area were recorded. Results: The highest MPS for the L-strut, DCC, curved L-strut, and C-curve was identified at the corner of the chondrotomy. The MPS at the corner of the chondrotomy was reduced 44% when comparing the C-curve with the traditional L-strut. The VMS patterns showed compressive stress along the caudal septum in all models, but at the corner, the stresses were highest in the chondrotomies designed with sharp-angled corners. The VMS showed a 76% decrease when comparing the C-curve with the traditional L-strut. The stress across the anterior septal angle is also higher in models with sharp-angled corners. Cartilage harvest volumetric and surface area assessments did not show meaningful differences between shapes. Conclusions and Relevance: The highest area of stress is near the transition of the dorsal to caudal septum in all models. Stresses are relatively higher in chondrotomy shapes that contain sharp-angled corners. The relative reduction in MPS and VMS utilizing a C-curve instead of an L-strut may decrease the likelihood that the septum will deform or fail in this region. The volume and surface area of the C-curve are similar to that of the L-strut technique. Avoiding sharp-angled corners reduces the stresses at the corner of the chondrotomy and across the anterior septal angle. Using a C-curve may be an improved septoplasty design.

Evaluation of the role of peripheral artery plaque geometry and composition on stent performance.

Peripheral stent fracture is a major precursor to restenosis of femoral artery atherosclerosis that has been treated with stent implantation. In this work, we validate a workflow for performing in silico stenting on a patient specific peripheral artery with heterogeneous plaque structure. Six human cadaveric femoral arteries were imaged ex vivo using intravascular ultrasound virtual histology (IVUS-VH) to obtain baseline vessel geometry and plaque structure. The vessels were then stented and the imaging repeated to obtain the stented vessel lumen area. Finite element (FE) models were then constructed using the IVUS-VH images, where the material property constants for each finite element were calculated using the proportions of each plaque component in the element, as identified by the IVUS-VH images. A virtual stent was deployed in each FE model, and the model lumen area was calculated and compared to the experimental lumen area to validate the modeling approach. The model was then used to compare stent performance for heterogeneous and homogeneous artery models, to determine whether plaque geometry or composition had added effects on stent performance. We found that the simulated lumen areas were similar to the corresponding experimental values, despite using generic material constants. Additionally, the heterogeneous and homogeneous lumen areas were also similar, implying that plaque geometry is a stronger predictor of stent expansion performance than plaque composition. Comparing stent stress and strain for heterogeneous and homogeneous models, it was found that stress from these two models had a strong linear correlation, while the strain correlation was weaker but still present. This implies that stent performance may be predicted with a simple homogeneous material models accounting for overall geometry of the plaque, providing that stent fatigue is calculated using stress criteria.

Acoustic Properties of Axial and Centrifugal Flow Left Ventricular Assist Devices and Prediction of Pump Thrombosis.

OBJECTIVE: To characterize the properties of the audible tones produced by current left ventricular assist device (LVAD) pumps approved for use, and to ascertain if changes in those may be present in the setting of pump thrombosis. PATIENTS AND METHODS: From August 31, 2016, to January 16, 2020, LVAD recipients consented to have surface recordings obtained using a high-fidelity digital stethoscope. Audio data were analyzed using digital recording and editing software to produce an acoustic spectrogram by Fast Fourier transformation. RESULTS: Recordings were obtained in 53 patient encounters (27 HeartMate II, 19 HeartWare and 7 HeartMate 3). In 12 patients (9 HeartMate II, 3 HeartWare) there was a clinical concern for pump thrombosis. In all patients and pump models, a fundamental frequency was noted, and the second and third harmonics were also clearly detectable. Where thrombosis occurred in the HeartMate II pump, the absolute (normal -46.9 [-57.5,-42.9] dB vs thrombosis -41.4 [-49.8,-26.8] dB; P=.08) and relative (normal 0.72 [0.62, 0.92] vs thrombosis 0.95 [0.86, 1.24]; P=.01) third harmonic frequencies were increased in amplitude. Where paired data were available, an increase in the absolute and relative third harmonic frequencies was observed in all patients. In the case of the HeartWare device, a consistent difference in harmonic amplitudes in the setting of thrombosis could not be identified. CONCLUSION: A consistent pattern of fundamental and harmonic frequencies is common to all LVADs currently approved for use. Alterations in the amplitude of higher order harmonics may signal the onset of pump thrombosis in axial flow LVADs.

Morphological and Hemodynamic Changes during Cerebral Aneurysm Growth.

Computational fluid dynamics (CFD) has grown as a tool to help understand the hemodynamic properties related to the rupture of cerebral aneurysms. Few of these studies deal specifically with aneurysm growth and most only use a single time instance within the aneurysm growth history. The present retrospective study investigated four patient-specific aneurysms, once at initial diagnosis and then at follow-up, to analyze hemodynamic and morphological changes. Aneurysm geometries were segmented via the medical image processing software Mimics. The geometries were meshed and a computational fluid dynamics (CFD) analysis was performed using ANSYS. Results showed that major geometry bulk growth occurred in areas of low wall shear stress (WSS). Wall shape remodeling near neck impingement regions occurred in areas with large gradients of WSS and oscillatory shear index. This study found that growth occurred in areas where low WSS was accompanied by high velocity gradients between the aneurysm wall and large swirling flow structures. A new finding was that all cases showed an increase in kinetic energy from the first time point to the second, and this change in kinetic energy seems correlated to the change in aneurysm volume.

Ex Vivo Evaluation of IVUS-VH Imaging and the Role of Plaque Structure on Peripheral Artery Disease.

Peripheral artery disease (PAD) results from the buildup of atherosclerotic plaque in the arterial wall, can progress to severe ischemia and lead to tissue necrosis and limb amputation. We evaluated a means of assessing PAD mechanics ex vivo using ten human peripheral arteries with PAD. Pressure-inflation testing was performed at six physiological pressure intervals ranging from 10-200 mmHg. These vessels were imaged with IVUS-VH to determine plaque composition and change in vessel structure with pressure. Statistical analysis was performed to determine which plaque structures and distributions of these structures had the greatest influence on wall deformation. We found that fibrous plaque, necrotic core, and calcification had a statistically significant effect on all variables (p<0.05). The presence of large concentrations of fibrous plaque was linked to reduced vessel compliance and ellipticity, which could lead to stent fractures and restenosis. For the plaque distribution we found that clustered necrotic core increased overall compliance while clustered calcification decreased overall compliance. The effect of plaque distribution on vessel wall deformation must be considered equally important to plaque concentration.

Patient specific characterization of artery and plaque material properties in peripheral artery disease.

Patient-specific finite element (FE) modeling of atherosclerotic plaque is challenging, as there is limited information available clinically to characterize plaque components. This study proposes that for the limited data available in vivo, material properties of plaque and artery can be identified using inverse FE analysis and either a simple neo-Hookean constitutive model or assuming linear elasticity provides sufficient accuracy to capture the changes in vessel deformation, which is the available clinical metric. To test this, 10 human cadaveric femoral arteries were each pressurized ex vivo at 6 pressure levels, while intravascular ultrasound (IVUS) and virtual histology (VH) imaging were performed during controlled pull-back to determine vessel geometry and plaque structure. The VH images were then utilized to construct FE models with heterogeneous material properties corresponding to the vessel plaque components. The constitutive models were then fit to each plaque component by minimizing the difference between the experimental and the simulated geometry using the inverse FE method. Additionally, we further simplified the analysis by assuming the vessel wall had a homogeneous structure, i.e. lumping artery and plaque as one tissue. We found that for the heterogeneous wall structure, the simulated and experimental vessel geometries compared well when the fitted neo-Hookean parameters or elastic modulus, in the case of linear elasticity, were utilized. Furthermore, taking the median of these fitted parameters then inputting these as plaque component mechanical properties in the finite element simulation yielded differences between simulated and experimental geometries that were on average around 2% greater (1.30-5.55% error range to 2.33-11.71% error range). For the homogeneous wall structure the simulated and experimental wall geometries had an average difference of around 4% although when the difference was calculated using the median fitted value this difference was larger than for the heterogeneous fits. Finally, comparison to uniaxial tension data and to literature constitutive models also gave confidence to the suitability of this simplified approach for patient-specific arterial simulation based on data that may be acquired in the clinic.

Optimizing Accuracy of Proximal Femur Elastic Modulus Equations.

Quantitative computed tomography-based finite element analysis (QCT/FEA) is a promising tool to predict femoral properties. One of the modeling parameters required as input for QCT/FEA is the elastic modulus, which varies with the location-dependent bone mineral density (ash density). The aim of this study was to develop optimized equations for the femoral elastic modulus. An inverse QCT/FEA method was employed, using an optimization process to minimize the error between the predicted femoral stiffness values and experimental values. We determined optimal coefficients of an elastic modulus equation that was a function of ash density only, and also optimal coefficients for several other equations that included along with ash density combinations of the variables sex and age. All of the optimized models were found to be more accurate than models from the literature. It was found that the addition of the variables sex and age to ash density made very minor improvements in stiffness predictions compared to the model with ash density alone. Even though the addition of age did not remarkably improve the statistical metrics, the effect of age was reflected in the elastic modulus equations as a decline of about 9% over a 60-year interval.

Mechanical testing setups affect spine segment fracture outcomes.

The purpose of the work presented here was to establish an experimental testing configuration that would generate a bending compression fracture in a laboratory setting. To this end, we designed and fabricated a fixture to accommodate a three level spine segment and to be able to perform mechanical testing by applying an off-centric compressive loading to create a flexion-type motion. Forces and moments occurring during testing were measured with a six-channel load cell. The initial testing configuration (Fixture A) included plates connected to the superior potted vertebral body and to the ball-socket joint of the testing system ram. Surprisingly, while all cadaveric specimens underwent a similar off-centric compressive loading, most of the specimens showed extension outcomes as opposed to the intended pure-flexion motion. The extension was due to fixture size and weight; by applying an off-centric load directly on the top plate, unintended large shear forces were generated. To resolve the issue, several modifications were made to the original fixture configuration. These modifications included the removal of the superior plates and the implementation of wedges at the superior surface of the fixture (Fixture B). A synthetic sample was used during this modification phase to minimize the number of cadaveric specimens while optimizing the process. The best outcomes were consistently observed when a 15°-wedge was used to provide flexion-type loading. Cadaveric specimens were then experimentally tested to fracture using the modified testing configuration (Fixture B). A comparison between both fixtures, A and B, revealed that almost all biomechanical parameters, including force, moment, and displacement data, were affected by the testing setup. These results suggest that fixture design and implementation for testing is of extreme importance, and can influence the fracture properties and affect the intended motion.