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1.
J Mech Behav Biomed Mater ; 154: 106441, 2024 Jun.
Article En | MEDLINE | ID: mdl-38518510

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.


Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Animals , Cattle , Swine , Humans , Collagen/chemistry , Catheters , Pericardium , Stress, Mechanical , Aortic Valve
2.
Tissue Eng Part A ; 29(15-16): 413-423, 2023 08.
Article En | MEDLINE | ID: mdl-37130041

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.


Biocompatible Materials , Nanofibers , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Tissue Engineering , Nanofibers/chemistry , Polyurethanes/pharmacology , Endothelial Cells , Magnetic Phenomena , Coated Materials, Biocompatible/chemistry
3.
J Neurosurg ; 139(1): 150-156, 2023 07 01.
Article En | MEDLINE | ID: mdl-36681964

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.


Intracranial Aneurysm , Humans , Magnesium/chemistry , Iron , Absorbable Implants , Alloys/chemistry
4.
J Neurointerv Surg ; 15(2): 178-182, 2023 Feb.
Article En | MEDLINE | ID: mdl-35636949

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.


Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Humans , Child , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Absorbable Implants , Stents , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Treatment Outcome
5.
Acta Biomater ; 145: 416-426, 2022 06.
Article En | MEDLINE | ID: mdl-35367631

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.


Alloys , Zinc , Absorbable Implants , Alloys/chemistry , Alloys/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Corrosion , Materials Testing , Stents , Zinc/chemistry , Zinc/pharmacology
6.
J Vis Exp ; (179)2022 01 06.
Article En | MEDLINE | ID: mdl-35068481

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.


Atherosclerosis , Endothelial Progenitor Cells , Animals , Blood Coagulation , Cell- and Tissue-Based Therapy , Swine , Tissue Engineering/methods
7.
J Mech Behav Biomed Mater ; 125: 104927, 2022 01.
Article En | MEDLINE | ID: mdl-34740008

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.


Atherosclerosis , Finite Element Analysis , Humans
8.
Med Eng Phys ; 98: 20-27, 2021 12.
Article En | MEDLINE | ID: mdl-34848034

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.


Elasticity Imaging Techniques , Heart Ventricles , Anisotropy , Elasticity , Elasticity Imaging Techniques/methods , Finite Element Analysis , Humans , Viscosity
9.
Brain Sci ; 11(4)2021 Apr 19.
Article En | MEDLINE | ID: mdl-33921861

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.

10.
Mayo Clin Proc ; 96(4): 887-900, 2021 04.
Article En | MEDLINE | ID: mdl-33814091

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.


Acoustics , Blood Circulation/physiology , Heart Failure/surgery , Heart-Assist Devices , Thrombosis/prevention & control , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
11.
J Mech Behav Biomed Mater ; 116: 104346, 2021 04.
Article En | MEDLINE | ID: mdl-33529996

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.


Coronary Artery Disease , Plaque, Atherosclerotic , Coronary Vessels , Femoral Artery , Humans , Plaque, Atherosclerotic/diagnostic imaging , Stents , Ultrasonography, Interventional
12.
Facial Plast Surg Aesthet Med ; 23(2): 90-97, 2021.
Article En | MEDLINE | ID: mdl-32721238

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.


Finite Element Analysis , Models, Anatomic , Nasal Cartilages/surgery , Nasal Septum/surgery , Rhinoplasty/methods , X-Ray Microtomography , Biomechanical Phenomena , Humans , Nasal Cartilages/anatomy & histology , Nasal Cartilages/diagnostic imaging , Nasal Septum/anatomy & histology , Nasal Septum/diagnostic imaging , Stress, Mechanical
13.
Article En | MEDLINE | ID: mdl-34291202

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.

14.
J Mech Behav Biomed Mater ; 101: 103453, 2020 01.
Article En | MEDLINE | ID: mdl-31585351

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.


Femoral Artery/pathology , Finite Element Analysis , Patient-Specific Modeling , Peripheral Arterial Disease/pathology , Humans , Pressure
15.
J Mech Behav Biomed Mater ; 100: 103399, 2019 12.
Article En | MEDLINE | ID: mdl-31479817

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.


Fracture Healing , Spinal Fractures/physiopathology , Aged , Biomechanical Phenomena , Bone Plates , Cadaver , Compressive Strength , Female , Humans , Male , Materials Testing , Mechanical Phenomena , Middle Aged , Motion , Range of Motion, Articular , Rotation , Shear Strength , Stress, Mechanical , Treatment Outcome
16.
Int J Comput Assist Radiol Surg ; 14(10): 1795-1804, 2019 Oct.
Article En | MEDLINE | ID: mdl-31054128

PURPOSE: Assessing the rupture probability of intracranial aneurysms (IAs) remains challenging. Therefore, hemodynamic simulations are increasingly applied toward supporting physicians during treatment planning. However, due to several assumptions, the clinical acceptance of these methods remains limited. METHODS: To provide an overview of state-of-the-art blood flow simulation capabilities, the Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was conducted. Seventeen research groups from all over the world performed segmentations and hemodynamic simulations to identify the ruptured aneurysm in a patient harboring five IAs. Although simulation setups revealed good similarity, clear differences exist with respect to the analysis of aneurysm shape and blood flow results. Most groups (12/71%) included morphological and hemodynamic parameters in their analysis, with aspect ratio and wall shear stress as the most popular candidates, respectively. RESULTS: The majority of groups (7/41%) selected the largest aneurysm as being the ruptured one. Four (24%) of the participating groups were able to correctly select the ruptured aneurysm, while three groups (18%) ranked the ruptured aneurysm as the second most probable. Successful selections were based on the integration of clinically relevant information such as the aneurysm site, as well as advanced rupture probability models considering multiple parameters. Additionally, flow characteristics such as the quantification of inflow jets and the identification of multiple vortices led to correct predictions. CONCLUSIONS: MATCH compares state-of-the-art image-based blood flow simulation approaches to assess the rupture risk of IAs. Furthermore, this challenge highlights the importance of multivariate analyses by combining clinically relevant metadata with advanced morphological and hemodynamic quantification.


Aneurysm, Ruptured/diagnosis , Cerebral Angiography , Intracranial Aneurysm/diagnosis , Models, Cardiovascular , Aneurysm, Ruptured/physiopathology , Cerebral Angiography/methods , Cerebrovascular Circulation/physiology , Computational Biology , Hemodynamics/physiology , Humans , Intracranial Aneurysm/physiopathology , Risk Assessment , Risk Factors
17.
Ann Biomed Eng ; 47(6): 1391-1399, 2019 Jun.
Article En | MEDLINE | ID: mdl-30887275

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.


Algorithms , Elastic Modulus , Femur/physiology , Adult , Aged , Aged, 80 and over , Female , Femur/diagnostic imaging , Finite Element Analysis , Humans , Male , Middle Aged , Tomography, X-Ray Computed
18.
Cardiovasc Eng Technol ; 10(1): 80-94, 2019 03.
Article En | MEDLINE | ID: mdl-30311149

PURPOSE: Tissue engineered heart valves (TEHV) are being investigated to address the limitations of currently available valve prostheses. In order to advance a wide variety of TEHV approaches, the goal of this study was to develop a cardiac valve bioreactor system capable of conditioning living valves with a range of hydrodynamic conditions as well as capable of assessing hydrodynamic performance to ISO 5840 standards. METHODS: A bioreactor system was designed based on the Windkessel approach. Novel features including a purpose-built valve chamber and pressure feedback control were incorporated to maintain asepsis while achieving a range of hydrodynamic conditions. The system was validated by testing hydrodynamic conditions with a bioprosthesis and by operating with cell culture medium for 4 weeks and living cells for 2 weeks. RESULTS: The bioreactor system was able to produce a range of pressure and flow conditions from static to resting adult left ventricular outflow tract to pathological including hypertension. The system operated aseptically for 4 weeks and cell viability was maintained for 2 weeks. The system was also able to record the pressure and flow data needed to calculate effective orifice area and regurgitant fraction. CONCLUSIONS: We have developed a single bioreactor system that allows for step-wise conditioning protocols to be developed for each unique TEHV design as well as allows for hydrodynamic performance assessment.


Bioprosthesis , Bioreactors , Cell Culture Techniques/instrumentation , Heart Valve Prosthesis , Heart Valves/physiology , Tissue Engineering/instrumentation , Animals , Cell Survival , Equipment Design , Humans , Hydrodynamics , Mice , NIH 3T3 Cells , Prosthesis Design , Time Factors
19.
Cardiovasc Eng Technol ; 9(4): 565-581, 2018 12.
Article En | MEDLINE | ID: mdl-30191538

PURPOSE: Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. METHODS: To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. RESULTS: Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. CONCLUSIONS: MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.


Cerebral Angiography/methods , Cerebrovascular Circulation , Hemodynamics , Intracranial Aneurysm/diagnostic imaging , Middle Cerebral Artery/diagnostic imaging , Models, Cardiovascular , Patient-Specific Modeling , Aneurysm, Ruptured/diagnostic imaging , Aneurysm, Ruptured/etiology , Aneurysm, Ruptured/physiopathology , Blood Flow Velocity , Female , Humans , Imaging, Three-Dimensional , Intracranial Aneurysm/complications , Intracranial Aneurysm/physiopathology , Middle Aged , Middle Cerebral Artery/physiopathology , Predictive Value of Tests , Prognosis , Radiographic Image Interpretation, Computer-Assisted , Regional Blood Flow , Reproducibility of Results , Risk Assessment , Risk Factors , Stress, Mechanical , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/etiology , Subarachnoid Hemorrhage/physiopathology
20.
Bone ; 116: 196-202, 2018 11.
Article En | MEDLINE | ID: mdl-30096469

Many researchers have used cadaveric fracture tests to determine the relationship between proximal femur (hip) fracture strength and a multitude of possible explanatory variables, typically considered one or two at a time. These variables include subject-specific proximal femur variables such as femoral neck areal bone mineral density (aBMD), sex, age, and geometry, as well as physiological hip fracture event variables such as fall speed and angle of impact. However, to our knowledge, no study has included all of these variables simultaneously in the same experimental dataset. To address this gap, the present study simultaneously included all of these subject-specific and fracture event variables in multivariate models to understand their contributions to femoral strength and fracture type. The primary aim of this study was to determine not only whether each of these variables contributed to the prediction of femoral strength, but also to determine the relative importance of each variable in strength prediction. A secondary aim was to similarly characterize the importance of these variables for the prediction of fracture type. To accomplish these aims, we characterized 197 proximal femurs (covering a wide range of subject-specific variables) with DXA and CT scans, and then tested the femurs to fracture in a sideways fall on the hip configuration. Each femur was tested using one of three fall speed conditions and one of four angles of impact (bone orientations). During each test, we acquired measurements of relevant force and displacement data. We then reduced the test data to determine femoral strength, and we used post-fracture CT scans to classify the fracture type (e.g., trochanteric, cervical). Using these results, the explanatory variables were analyzed with mixed statistical models to explain variations in hip fracture strength and fracture type, respectively. Five explanatory variables were statistically significant in explaining the variability in femoral strength: aBMD, sex, age, fall speed, and neck-shaft angle (P ≤ 0.0135). These five variables, including significant interactions, explained 80% of the variability in hip fracture strength. Additionally, when only aBMD, sex, and age (P < 0.0001) were considered in the model, again including significant interactions, these three variables alone explained 79% of the variability in hip fracture strength. So while fall speed (P = 0.0135) and neck-shaft angle (P = 0.0041) were statistically significant, the inclusion of these variables did not appreciably improve the prediction of hip fracture strength compared to the model that considered only aBMD, sex and age. For the variables we included in this study, in the ranges we considered, our findings indicate that the clinically-available information of patient age, sex and aBMD are sufficient for femoral strength assessment. These findings also suggest that there is little value in the extra effort required to characterize the effect of femoral geometry on strength, or to account for the probabilistic nature of fall-related factors such as fall speed and angle of impact. For fracture type, the only explanatory variable found to be significant was aBMD (P ≤ 0.0099). We found that the odds of having intertrochanteric fractures increased by 47% when aBMD decreased by one standard deviation (0.2 g/cm2).


Femoral Fractures/epidemiology , Femoral Fractures/pathology , Aged , Biomechanical Phenomena , Cadaver , Cohort Studies , Female , Humans , Male , Multivariate Analysis , Risk Factors
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