Name: experimental investigation of secondary flow structures downstream of a model type iv stent failure in a 180° curved artery test section
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Description: Watch this Scientific Journal Video about Experimental Investigation of Secondary Flow Structures Downstream of a Model Type IV Stent Failure in a 180Â° Curved Artery Test Section at JoVE.com

The authors acknowledge support from NSF grant CBET-0909678 and funding from the GW Center for Biomimetics and Bioinspired Engineering (COBRE). We thank the students, Mr. Christopher Popma, Ms. Leanne Penna, Ms. Shannon Callahan, Mr. Shadman Hussain, Mr. Mohammed R. Najjari, and Ms. Jessica Hinke for help in the laboratory and Mr. Mathieu Barraja for assisting in CAD drawings.

<ol>
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No conflicts of interest declared.

The protocol presented in this paper describes the acquisition of high fidelity experimental data using particle image velocimetry technique (PIV) and coherent structure detection methods, viz., continuous wavelet transforms, <img alt="Equation 1" src="/files/ftp_upload/51288/51288eq1.jpg" />, suited for identification of vortex and shear-dominated flows. Analysis of experimental data from physiological inflows in the presence of an idealized &#34;Type IV&#34; fracture reveals that secondary flow structures with complicated hydrodynamic effects such as flow structure asymmetry and variation in spatio-temporal distributions that cannot be predicted from simple fluid dynamic theories.
There are four critical steps in the execution of this protocol viz., (i) Design and fabrication of laboratory-scale stent models, (ii) Preparation of a blood analog working fluid matched with kinematic viscosity of blood and refractive index of the curved artery model, (iii) Non-invasive experimental arrangement (2C-2D PIV) and (iv) Advanced coherent structure detection methods for identifying arterial blood flow patterns.
Womersley number is a dimensionless parameter that relates pulsatile flow frequency to viscous effects 7. Reynolds number relates inertial forces to viscous flow forces. Dean number relates centripetal forces that arise in flow through curved pipes to inertial and viscous forces 1, 2. Details pertaining to the scaling of the physiological waveform with Womersley and Reynolds numbers are presented in 5, 6. The inflow waveform used in this study was reconstructed from archetypal carotid artery flow rate measurements (averaged) of 17-20 healthy patients by Holdworth et al. 15. The pipes leading to the curved artery test section are long enough to allow the flow to be fully developed such that the pulsatile flow conditions at the inlet to the curved artery test section are in-phase with the pump (Figures 3a, 3b and 4a). Repeatability of supplied physiological waveform was ensured by making axial PIV measurements of flow rate and bulk velocity upstream to the model artery using a 2C-2D PIV system (see Fig. 4b).
The hydrodynamic stimuli from arterial hemodynamics toward the aforementioned clinical complications are not well known. Physiological flows involving stent and stent-fractures pose complexities for in vivo and in vitro measurements. The protocol presented herein can be modified to include compliance in the pipes to study the influence of arterial secondary flow structures under non-ideal and more realistic flow scenarios. Such experiments will pose additional challenges in measurement and post-processing of data. The use of stereo- or tomographic-PIV techniques, capable of mapping three-dimensional velocity fields can significantly improve our understanding of the dynamics of secondary flow structures.
The limitations of the experimental arrangement lie in the lack resolution in the near-wall (model-artery lumen) regions and the lack of optical access to the blood flow within the stent implanted regions. These limitations however, pose elegant extensions of the protocol presented. The use of optically clear material for 3D-printing of stents, realistic and patient-specific arterial geometries would allow unprecedented access to hemodynamics of stent-implants and fractured-stents.
An extended outcome of the protocol presented herein relates to the selection of the &#34;best&#34; wavelet scale for coherent structure detection. Steps 5.6.3 - 5.6.7 are a suggested solution to the problem of the &#34;best&#34; wavelet scale (or basis function) in coherent structure detection. The authors found that following steps 5.6.3 - 5.6.7 resolved all the large-scale coherent structures and in addition, detected smaller scale coherent structures that were hitherto undetected in curved artery model experiments. The authors suggest Ref. 34, 35 wherein Shannon entropy is used to evaluate the &#34;best&#34; basis in a discrete wavelet packet transform (DWPT) algorithm toward detecting coherent structures in a turbulent flow experiment. For further information on the approach pertaining to a continuous wavelet transform algorithm, the authors suggest Ref. 5, 6, 35 and the references cited therein.
The incidence of fractures in stent implants and concomitant flow perturbations result in secondary flow structures with complex, multi-scale morphologies and varying size-strength characteristics. Significance of the methodologies such as particle image velocimetry (PIV) in combination with coherent structure detection especially, wavelet transforms allows for resolution of multi-scale, multi-strength secondary flow structures under stent and stent-fracture-induced flow scenarios. The protocol presented herein paves the way for investigating medical complications such as in-stent restenosis (ISR), stent thrombosis and aneurysm formation 8, 11 - 14 due to secondary flows. In addition, secondary flow vortical patterns encountered in the core regions will tend to affect the motion and exposure time of blood-borne particles such as platelets, sensitizing them for activation toward thrombosis. Strain-dominated near-wall (lumen) secondary flow structures will ultimately influence wall shear stress that is closely related to atherogenesis, especially in arterial curvatures.
The analytical procedures to predict secondary flow (vortical) structures are complicated, requiring Navier-Stokes equations in toroidal coordinates and asymptotic theories 1 - 3, 7. A combination of experiments and higher order analytical methods will promote new insights into the hemodynamics of curved arteries prone to several cardiovascular diseases and clinical complication associated with stent implantations and stent fractures.

Secondary flow structures are vortical flow patterns that occur in internal flow geometries with curvatures such as curved pipes and channels. These vortical structures arise due to the combined action of centrifugal forces, adverse pressure gradients and inflow characteristics. In general, secondary flow structures appear in planar cross-sections of curved pipes as symmetric Dean-type vortices under steady inflow and, symmetric Dean- and Lyne-type vortices under oscillatory inflow conditions 1 - 3. Secondary flow morphologies are greatly affected by pulsatility and multiple harmonics of pulsatile, physiological inflow conditions. These structures acquire markedly different size-strength-shape characteristics compared to non-physiological (steady and oscillatory) flows 1 - 6. Atherosclerotic lesion development in arteries is affected by the existence of high frequency shear oscillations in regions experiencing low mean shear 27, 28. Secondary flow structures may influence the progress of diseases such as atherosclerosis and possibly, mediate the endothelial response due to pulsatile blood flow by altering wall shear stresses and exposure times of blood-borne particles.
A common treatment to atherosclerosis, a complication resulting in narrowing of arteries by obstructive lesions, is the implantation of stents. Stent fractures are structural failures of implanted stents that lead to further medical complications such as in-stent restenosis (ISR), stent thrombosis and aneurysm formation 9 - 13. Stent fractures have been categorized into various failure &#34;Types I-to-IV&#34;, wherein &#34;Type IV&#34; characterizes the highest clinical severity and is defined as the complete transverse fracture of stent struts along with linear displacements of the stent fragments 14. The protocol presented in this study describes an experimental method of visualization of secondary flow structures downstream of an idealized &#34;Type IV&#34; stent fracture in a curved artery model.
The suggested protocol has the following four essential features:
Design and fabrication of laboratory-scale stent models: Geometric description of stents can be associated with a set of self-expandable spirals (springs or helices) intertwined using Nitinol (an alloy of nickel and titanium) wires 29. The length of the stent and its strut diameter depend on the length scale of arterial lesions encountered during clinical implantation 5. Parametric variation of strut diameter and the rising of the winding (or pitch) leads to stents of various geometric configurations. A summary of stent design parameters chosen for 3D printing are presented in Table 1.
Preparation of a blood analog working fluid matched with kinematic viscosity of blood and refractive index of the test section: Optical access to the curved artery test section is required in order to make non-invasive velocity measurements. Accordingly, a Newtonian blood-mimicking working fluid with the refractive index of the vascular model and ideally, a dynamic viscosity, matching human blood is used to obtain accurate blood flow measurements 16 - 18, 30. The working fluid used in this study was reported by Deutsch et al. (2006), that comprised of 79% saturated aqueous sodium iodide (NaI), 20% pure glycerol, and 1% water (by volume)16.
Experimental arrangement for the detection of coherent secondary flow structures using a two-component, two-dimensional particle image velocimetry (2C-2D PIV): Experiments were designed to acquire phase-averaged secondary flow velocity data at various planar cross-sectional locations downstream of a combination of straight and curved stent sections embodying an idealized &#34;Type IV&#34; stent fracture 5, 6, 9, 14. The protocol-steps pertaining to the acquisition of secondary flow velocity fields using particle image velocimetry (PIV) technique involves a PIV system that comprises of a laser (light sheet) source, optics to focus and illuminate the regions of flow, a special cross-correlation charge coupled device (CCD-sensor or camera) and tracer particles to be illuminated by the light sheet within a short time interval (&#916;t; see Table 4) 31, 32.
The steps in the protocol assume the following: First, a calibrated, experimental set-up of a two-component, two-dimensional (2C-2D) PIV system that evaluates images by double-frame, single-exposure recordings. Second, the 2C-2D PIV system calculates the mean displacements of tracer particles by performing cross-correlation between two image frames acquired during each recording. A brief summary of PIV specifications and image acquisition software is presented in the materials and equipment table. Third, all safety precautions needed to operate the laser are followed by trained laboratory personnel according to the guidelines provided by the host institution. The authors suggest Refs. 31 and 32 for a holistic understanding of the implementation, functionality and application of PIV technique in aero-, hydro- and microfluid dynamics, correlation peak detection and displacement estimation, material and density of tracer particles and, measurement noise and accuracy. Also note that the laser and camera can be controlled by the PIV data acquisition computer (Figure 3A) and data processing software.
Data acquisition and post-processing for coherent structure detection: Phase-averaged secondary flow velocity measurements using a 2C-2D PIV were generated using the protocol description that follows. Post-processing of the data involved coherent secondary flow structure detection using the following three methods: continuous wavelet transforms, <img alt="Equation 1" src="/files/ftp_upload/51288/51288eq1.jpg" /> 5, 6, 19 - 24, 26.
The authors note that the velocity gradient tensor is essentially, a 3 x 3 matrix, 
<img alt="Equation 2" src="/files/ftp_upload/51288/51288eq2.jpg" />.
The protocol presents a method of acquiring two-dimensional experimental measurements (from 2C-2D PIV technique). Therefore, full experimental access to the velocity gradient tensor will not be attainable using this method. The velocity gradient tensor for each pixel <img alt="Equation 3" src="/files/ftp_upload/51288/51288eq3.jpg" /> of the PIV image <img alt="Equation 4" src="/files/ftp_upload/51288/51288eq4.jpg" /> should be a 2 x 2 matrix, <img alt="Equation 5" src="/files/ftp_upload/51288/51288eq5.jpg" />. The z-component vorticity <img alt="Equation 6" src="/files/ftp_upload/51288/51288eq6.jpg" /> for each pixel <img alt="Equation 7" src="/files/ftp_upload/51288/51288eq7.jpg" /> is computed using the anti-symmetric part of the velocity gradient tensor <img alt="Equation 8" src="/files/ftp_upload/51288/51288eq8.jpg" />. The result will be a 2D array of vorticity <img alt="Equation 9" src="/files/ftp_upload/51288/51288eq9.jpg" /> that can be visualized in a contour plot. The authors strongly suggest Ref. 25 for an eloquent discussion experimental access to the velocity gradient tensor toward enhancing the knowledge of vorticity dissipation, strain rates and coherent structure detection. Furthermore, the authors do not attempt to explore the inter-relationships between the aforementioned coherent structure detection methods and suggest Ref. 23, 24 for a comprehensive discussion on that subject.
The focus of the steps in the protocol is the quantitative identification of secondary flow (vortical) structures (also known as coherent structures). Three methods of coherent structure detection viz., <img alt="Equation 10" src="/files/ftp_upload/51288/51288eq10.jpg" /> and wavelet transformed vorticity <img alt="Equation 11" src="/files/ftp_upload/51288/51288eq11.jpg" /> are applied to velocity field data toward detection of multi-scale, multi-strength occurrences of secondary flow structures downstream of the idealized &#34;Type IV&#34; stent fracture.
The <img alt="Equation 12" src="/files/ftp_upload/51288/51288eq12.jpg" />, defines a vortex as a spatial region where the Euclidean norm of the vorticity tensor dominates that of the rate of strain 19, 23, 24.The velocity gradient matrix is decomposed into symmetric (strain rate) and anti-symmetric (rotation) parts. Eigenvalues of strain rate matrix are computed; <img alt="Equation 13" src="/files/ftp_upload/51288/51288eq13.jpg" />. Norm of the strain rate is then calculated; <img alt="Equation 14" src="/files/ftp_upload/51288/51288eq14.jpg" />. Vorticity is computed from the anti- symmetric part. Enstrophy or square of z-component vorticity, <img alt="Equation 15" src="/files/ftp_upload/51288/51288eq15.jpg" />) is then computed. The <img alt="Equation 16" src="/files/ftp_upload/51288/51288eq16.jpg" /> is finally computed; <img alt="Equation 17" src="/files/ftp_upload/51288/51288eq17.jpg" />. A contour plot of the entire set of <img alt="Equation 18" src="/files/ftp_upload/51288/51288eq18.jpg" /> with iso-regions of <img alt="Equation 19" src="/files/ftp_upload/51288/51288eq19.jpg" />, will indicate secondary flow structures 19. 
The <img alt="Equation 20" src="/files/ftp_upload/51288/51288eq20.jpg" />, also known as &#39;swirling strength&#39; is a vortex identification method performed by critical-point analysis of the local velocity gradient tensor and its corresponding eigenvalues 20 - 24. Eigenvalues of the velocity gradient tensor at each pixel&#160;<img alt="Equation 21" src="/files/ftp_upload/51288/51288eq21.jpg" /> are computed. The eigenvalues should be of the form, <img alt="Equation 22" src="/files/ftp_upload/51288/51288eq22.jpg" />. A contour plot of <img alt="Equation 23" src="/files/ftp_upload/51288/51288eq23.jpg" /> with iso-regions of <img alt="Equation 24" src="/files/ftp_upload/51288/51288eq24.jpg" /> will indicate secondary flow structures 20 - 22.
Wavelet transform method utilizes an analyzing function (or wavelet) that has smoothness in physical and spectral spaces, is admissible (or has zero mean) and has a finite <img alt="Equation 25" src="/files/ftp_upload/51288/51288eq25.jpg" />5, 6, 26. By convolving a dilated or contracted wavelet with a 2D vorticity field, wavelet transformed vorticity&#160;<img alt="Equation 26" src="/files/ftp_upload/51288/51288eq26.jpg" /> field is generated comprising of coherent structures with a wide range of scales and strengths 5, 6, 26. Shannon entropy of the 2D wavelet-transformed vorticity field is computed to estimate the optimal wavelet scale at which all the coherent structures are adequately resolved. This entropy estimation involves a set of probabilities <img alt="Equation 27" src="/files/ftp_upload/51288/51288eq27.jpg" /> for each pixel <img alt="Equation 21" src="/files/ftp_upload/51288/51288eq21.jpg" /> such that&#160; <img alt="Equation 28" src="/files/ftp_upload/51288/51288eq28.jpg" />, the normalized square modulus of the vorticity associated with the pixel at location m, n 5, 6. The procedural steps are presented graphically in Figure 6. The restrictions placed on the choice of the wavelet are presented in detail in Ref. 26. This protocol step describes the procedure for coherent structure detection using a 2D Ricker wavelet. The justification for the use of this wavelet for vortical pattern matching is presented in Ref. 5, 6 and the pertinent references cited therein.

<table><tbody><tr><td>Acrylic tubes and sheet</td><td>McMaster-Carr Supply Company</td><td></td><td>Inlet and outlet pipes and material of the curved artery test section</td></tr><tr><td>Object24 Desktop 3D printer</td><td>Stratasys</td><td></td><td>Desktop rapid prototyping machine. http://www.stratasys.com</td></tr><tr><td>VeroWhitePlus Opaque material</td><td>Stratasys</td><td></td><td>Building material for Object24 Desktop 3D printer</td></tr><tr><td>Fullcure 705</td><td>Stratasys</td><td></td><td>Non-toxic gel-like photopolymer Support material for Object24 Desktop 3D printer</td></tr><tr><td>Ubbelohde viscometer</td><td>Cole Parmer</td><td>YO-98934-12</td><td>Toward measurement of kinematic viscosity of the blood-analog fluid</td></tr><tr><td>VELP scientifica - ESP stirrer&amp;nbsp;</td><td>VELP Scientifica</td><td>F206A0179</td><td>Magnetic stirrer</td></tr><tr><td>Ohaus Scout Pro SP 601&amp;nbsp;</td><td>The Lab Depot</td><td>SP4001</td><td>Weigh scale</td></tr><tr><td>Refractometer</td><td>Atago</td><td>PAL-RI</td><td>Toward measurement of refractive index of blood-analog fluid</td></tr><tr><td>Beakers, pipettes, syringes and spatula</td><td>Sigma-Aldrich&amp;nbsp;</td><td>CLS710110,&amp;nbsp; CLS10031L, CLS71015, CLS71011 Z193216</td><td>Toward handling materials required for blood-analog solution preparation</td></tr><tr><td>Sodium Iodide</td><td>Sigma-Aldrich</td><td>383112-2.5KG&amp;nbsp;</td><td>Crystalline</td></tr><tr><td>Glycerol</td><td>Sigma-Aldrich</td><td>G5516-1L</td><td>Liquid</td></tr><tr><td>Deionized Water</td><td>-</td><td>-</td><td>Liquid</td></tr><tr><td>Sodium thiosulfate anhydrous</td><td>Sigma-Aldrich</td><td>72049-250G</td><td>Powder</td></tr><tr><td>PIV Recording medium</td><td>LaVision</td><td>Imager Intense 10Hz</td><td>PIV Image acquisition CCD camera</td></tr><tr><td>PIV Illumination source</td><td>New Wave Research</td><td>Solo III-15</td><td>PIV Laser source, Nd:YAG laser, 532 nm, dual pulse 70 mJ/pulse</td></tr><tr><td>PIV Imaging software</td><td>LaVision</td><td>DaVis 7.2</td><td>PIV data acquisition and instrument control</td></tr><tr><td>PIV Seeding material</td><td>Thermo-scientific&amp;nbsp;&amp;nbsp;</td><td>Flouro-Max</td><td>Red fluorescent polymer microspheres (&amp;asymp; 7 &amp;micro;m); Dry dyed polystyrene (DVB) fluorescent microspheres emit bright and distinct colors when illuminated by the light of shorter&amp;nbsp; wavelengths than the emission wavelength.&amp;nbsp;</td></tr></tbody></table>

experimental investigation of secondary flow structures downstream of a model type iv stent failure in a 180&#176; curved artery test section

The arterial network in the human vasculature comprises of ubiquitously present blood vessels with complex geometries (branches, curvatures and tortuosity). Secondary flow structures are vortical flow patterns that occur in curved arteries due to the combined action of centrifugal forces, adverse pressure gradients and inflow characteristics. Such flow morphologies are greatly affected by pulsatility and multiple harmonics of physiological inflow conditions and vary greatly in size-strength-shape characteristics compared to non-physiological (steady and oscillatory) flows 1 - 7.
Secondary flow structures may ultimately influence the wall shear stress and exposure time of blood-borne particles toward progression of atherosclerosis, restenosis, sensitization of platelets and thrombosis 4 - 6, 8 - 13. Therefore, the ability to detect and characterize these structures under laboratory-controlled conditions is precursor to further clinical investigations.
A common surgical treatment to atherosclerosis is stent implantation, to open up stenosed arteries for unobstructed blood flow. But the concomitant flow perturbations due to stent installations result in multi-scale secondary flow morphologies 4 - 6. Progressively higher order complexities such as asymmetry and loss in coherence can be induced by ensuing stent failures vis-&#224;-vis those under unperturbed flows 5. These stent failures have been classified as &#34;Types I-to-IV&#34; based on failure considerations and clinical severity 14.
This study presents a protocol for the experimental investigation of the complex secondary flow structures due to complete transverse stent fracture and linear displacement of fractured parts (&#34;Type IV&#34;) in a curved artery model. The experimental method involves the implementation of particle image velocimetry (2C-2D PIV) techniques with an archetypal carotid artery inflow waveform, a refractive index matched blood-analog working fluid for phase-averaged measurements 15 - 18. Quantitative identification of secondary flow structures was achieved using concepts of flow physics, critical point theory and a novel wavelet transform algorithm applied to experimental PIV data 5, 6, 19 - 26.

Watch this Scientific Journal Video about Experimental Investigation of Secondary Flow Structures Downstream of a Model Type IV Stent Failure in a 180Â° Curved Artery Test Section at JoVE.com

Experimental Investigation of Secondary Flow Structures Downstream of a Model Type IV Stent Failure in a 180&#176; Curved Artery Test Section

Stent implants in stenosed arterial curvatures are prone to "Type IV" failures involving the complete transverse fracture of stents and linear displacement of the fractured parts. We present a protocol for detection of secondary flow (vortical) structures in a curved artery model, downstream of clinically relevant "Type IV" stent failures.

The arterial network in the human vasculature comprises of ubiquitously present blood vessels with complex geometries (branches, curvatures and ...

experimental-investigation-secondary-flow-structures-downstream-model

Nanyang Technological University

Research

JoVE Journal

Bioengineering

11.6K Views.  The George Washington University. Stent implants in stenosed arterial curvatures are prone to "Type IV" failures involving the complete transverse fracture of stents and linear displacement of the fractured parts. We present a protocol for detection of secondary flow (vortical) structures in a curved artery model, downstream of clinically relevant "Type IV" stent failures.

Video: Experimental Investigation of Secondary Flow Structures Downstream of a Model Type IV Stent Failure in a 180° Curved Artery Test Section

Monitoring the Wall Mechanics During Stent Deployment in a Vessel

Clinical trials have reported different restenosis rates for various stent designs1. It is speculated that stent-induced strain concentrations on the arterial wall lead to tissue injury, which initiates restenosis2-7. This hypothesis needs further investigations including better quantifications of non-uniform strain distribution on the artery following stent implantation. A non-contact surface strain measurement method for the stented artery is presented in this work. ARAMIS stereo optical surface strain measurement system uses two optical high speed cameras to capture the motion of each reference point, and resolve three dimensional strains over the deforming surface8,9. As a mesh stent is deployed into a latex vessel with a random contrasting pattern sprayed or drawn on its outer surface, the surface strain is recorded at every instant of the deformation. The calculated strain distributions can then be used to understand the local lesion response, validate the computational models, and formulate hypotheses for further in vivo study.

Stent-induced arterial strain distributions are characterized using an optical surface strain measurement system. This visualization technique is used to gain insights into the impact of stent implantation on the host vessel.

Clinical trials have reported different restenosis rates for various stent designs1. It is speculated that stent-induced strain concentrations on the ...

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

A model of stent implantation in mouse carotid artery is described. Compared to other similar methods, this procedure is very rapid, simple and accessible, offering the possibility to study in a convenient way the vascular wall reaction to different drug-eluting stents and the molecular mechanisms of restenosis.

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

Medicine

Imaging In-Stent Restenosis: An Inexpensive, Reliable, and Rapid Preclinical Model

Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and future drug-eluting stents.
A variety of antibodies and transgenic and knockout strains are available in rats. Consequently, a model for in-stent restenosis in the rat would be convenient for pathobiological and pathophysiological studies. 
In this video, we present the full procedure and pit-falls of a rat stent model suitable for high throughput stent research. We will show the surgical procedure of stent deployment, and the assessment of in-stent restenosis using the most elegant technique of OCT (Optical Coherence Tomography). This technique provides high accuracy in assessing plaque CSAs (cross section areas) and correlates well with histological sections, which require special and time consuming embedding and sectioning techniques. OCT imaging further allows longitudinal monitoring of the development of in-stent restenosis within the same animal compared to one-time snapshots using histology.

This video demonstrates how to use a preclinical inexpensive and reliable model to study pathobiological and pathophysiological processes of in-stent restenosis development. Longitudinal in vivo monitoring using OCT (Optical Coherence Tomography) and analysis of OCT images are also demonstrated.

Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and ...

Biology

Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention

Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. The feasibility of using magnetic forces to capture and retain endothelial outgrowth cells (EOC) labeled with super paramagnetic iron oxide nanoparticles (SPION) has been shown previously. But this technique requires the development of a mechanically functional stent from a magnetic and biocompatible material followed by in-vitro and in-vivo testing to prove rapid endothelialization. We developed a weakly ferromagnetic stent from 2205 duplex stainless steel using computer aided design (CAD) and its design was further refined using finite element analysis (FEA). The final design of the stent exhibited a principal strain below the fracture limit of the material during mechanical crimping and expansion. One hundred stents were manufactured and a subset of them was used for mechanical testing, retained magnetic field measurements, in-vitro cell capture studies, and in-vivo implantation studies. Ten stents were tested for deployment to verify if they sustained crimping and expansion cycle without failure. Another 10 stents were magnetized using a strong neodymium magnet and their retained magnetic field was measured. The stents showed that the retained magnetism was sufficient to capture SPION-labeled EOC in our in-vitro studies. SPION-labeled EOC capture and retention was verified in large animal models by implanting 1 magnetized stent and 1 non-magnetized control stent in each of 4 pigs. The stented arteries were explanted after 7 days and analyzed histologically. The weakly magnetic stents developed in this study were capable of attracting and retaining SPION-labeled endothelial cells which can promote rapid healing.

Our goals were to design, manufacture and test ferromagnetic stents for endothelial cell capture. Ten stents were tested for fracture and 10 more stents were tested for retained magnetism. Finally, 10 stents were tested in-vitro and 8 more stents were implanted in 4 pigs to show cell capture and retention.

Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. ...

4D Printed Bifurcated Stents with Kirigami-Inspired Structures

Branched vessels, typically in the form of the letter &#34;Y,&#34;&#160;can be narrowed or blocked, resulting in serious health problems. Bifurcated stents, which are hollow in the interior and exteriorly shaped to the branched vessels, surgically inserted inside the branched vessels, act as a supporting structure so that bodily fluids can freely travel through the interior of the stents without being obstructed by the narrowed or blocked vessels. For a bifurcated stent to be deployed at the target site, it needs to be injected inside the vessel and travel within the vessel to reach the target site. The diameter of the vessel is much smaller than the bounding sphere of the bifurcated stent; thus, a technique is required so that the bifurcated stent remains small enough to travel through the vessel and expands at the targeted branched vessel. These two conflicting conditions, that is, small enough to pass through and large enough to structurally support narrowed passages, are extremely difficult to satisfy simultaneously. We use two techniques to fulfill the above requirements. First, on the material side, a shape memory polymer (SMP) is used to self-initiate shape changes from small to large, that is, being small when inserted and becoming large at the target site. Second, on the design side, a kirigami pattern is used to fold the branching tubes into a single tube with a smaller diameter. The presented techniques can be used to engineer structures that can be compacted during transportation and return to their functionally adept shape when activated. Although our work is targeted on medical stents, biocompatibility issues need to be solved before actual clinical use.

Using a 3D printer, a shape memory polymer filament is extruded to form a branched tubular structure. The structure is patterned and shaped such that it can contract into a compact form once folded and then return to its formed shape when heated.

Branched vessels, typically in the form of the letter &#34;Y,&#34;&#160;can be narrowed or blocked, resulting in serious health problems. Bifurcated ...

Engineering

In vitro Assessment of Aortic Regurgitation Using Four-Dimensional Flow Magnetic Resonance Imaging

Aortic regurgitation (AR) refers to backward blood flow from the aorta into the left ventricle (LV) during ventricular diastole. The regurgitant jet arising from the complex shape is characterized by the three-dimensional flow and high-velocity gradient, sometimes limiting an accurate measurement of the regurgitant volume using 2D echocardiography. Recently developed four-dimensional flow magnetic resonance imaging (4D flow MRI) enables three-dimensional volumetric flow measurements, which can be used to accurately quantify the amount of the regurgitation. This study focuses on (i) magnetic resonance compatible AR model fabrication (dilatation, perforation, and prolapse) and (ii) systematic analysis of the performance of 4D flow MRI in AR quantification. The results indicated that the formation of the forward and backward jets over time was highly dependent on the types of AR origin. The amount of regurgitation volume bias for the model types were -7.04%, -33.21%, 6.75%, and 37.04% compared to the ground truth (48 mL) volume measured from the pump stroke volume. The largest error of the regurgitation fraction was around 12%. These results indicate that careful selection of imaging parameters is required when absolute regurgitation volume is important. The suggested in vitro flow phantom can easily be modified to simulate other valvular diseases such as aortic stenosis or bicuspid aortic valve (BAV) and can be used as a standard platform to test different MRI sequences in the future.

In vitro Assessment of Aortic Regurgitation Using Four-Dimensional Flow Magnetic Resonance Imaging

Aortic regurgitation is an aortic valve heart disease. This manuscript demonstrates how four-dimensional flow magnetic resonance imaging can evaluate aortic regurgitation using in vitro heart valves mimicking aortic regurgitation.

Aortic regurgitation (AR) refers to backward blood flow from the aorta into the left ventricle (LV) during ventricular diastole. The regurgitant jet ...

Particle Image Velocimetry Investigation of Hemodynamics via Aortic Phantom

Aortic valve dysfunction and stroke have recently been reported in transcatheter aortic valve implantation (TAVI) patients. Thrombus in the aortic sinus and neo-sinus due to hemodynamic changes has been suspected. In vitro experiments help investigate the hemodynamic characteristics in the cases where an in vivo assessment proves to be limited. In vitro experiments are also more robust, and the variable parameters are controlled readily. Particle image velocimetry (PIV) is a popular velocimetry method for in vitro studies. It provides a high-resolution velocity field such that even small-scale flow features are observed. The purpose of this study is to show how PIV is used to investigate the flow field in the aortic sinus after TAVI. The in vitro setup of the aortic phantom, TAVI for PIV, and the data acquisition process and post-processing flow analysis are described. The hemodynamic parameters are derived, including the velocity, flow stasis, vortex, vorticity, and particle residence. The results confirm that in vitro experiments and PIV help investigate the hemodynamic features in the aortic sinus.

Particle Image Velocimetry Investigation of Hemodynamics via Aortic Phantom

The present protocol describes particle image velocimetry (PIV) measurements performed to investigate the sinus flow through the in vitro setup of the transcatheter aortic valve (TAV). The hemodynamic parameters based on velocity are also determined.

Aortic valve dysfunction and stroke have recently been reported in transcatheter aortic valve implantation (TAVI) patients. Thrombus in the aortic sinus ...

 IVUS-Based Computational Method to Quantify Coronary Mechanical Properties

Intravascular Ultrasound Image-Based Finite Element Modeling Approach for Quantifying In Vivo Mechanical Properties of Human Coronary Artery

Quantifying the mechanical properties of coronary arterial walls could provide meaningful information for the diagnosis, management, and treatment of coronary artery diseases. Since patient-specific coronary samples are not available for patients requiring continuous monitoring, direct experimental testing of vessel material properties becomes impossible. Current coronary models typically use material parameters from available literature, leading to significant mechanical stress/strain calculation errors. Here, we would introduce a finite element model-based updating approach (FEMBUA) to quantify patient-specific in vivo material properties of coronary arteries based on medical images. In vivo cine intravascular ultrasound (IVUS) and virtual histology (VH)-IVUS images of coronary arteries were acquired from a patient with coronary artery disease. Cine IVUS images showing the vascular movement over one cardiac cycle were segmented, and two IVUS frames with maximum and minimum lumen circumferences were selected to represent the coronary geometry under systolic and diastolic pressure conditions, respectively. VH-IVUS image was also segmented to obtain the vessel contours, and a layer thickness of 0.05 cm was added to the VH-IVUS contours to reconstruct the coronary geometry. A computational finite element model was created with an anisotropic Mooney-Rivlin material model used to describe the vessel's mechanical properties and pulsatile blood pressure conditions prescribed to the coronary luminal surface to make it contract and expand. Then, an iterative updating approach was employed to determine the material parameters of the anisotropic Mooney-Rivlin model by matching minimum and maximum lumen circumferences from the computational finite element model with those from cine IVUS images. This image-based finite element model-based updating approach could be successfully extended to determine the material properties of arterial walls in various vascular beds and holds the potential for risk assessment of cardiovascular diseases.

In vivo cine intravascular ultrasound images show the coronary cross-sectional movement corresponding to different pressure loading conditions. Based on a finite element model, an iterative scheme was employed to determine the patient-specific mechanical properties of coronary arteries in vivo by matching coronary motion from the computational model and medical images.

Quantifying the mechanical properties of coronary arterial walls could provide meaningful information for the diagnosis, management, and treatment of ...

Optical Coherence Tomography Based Biomechanical Fluid-Structure Interaction Analysis of Coronary Atherosclerosis Progression

In this paper, we present a complete workflow for the biomechanical analysis of atherosclerotic plaque in the coronary vasculature. With atherosclerosis as one of the leading causes of global death, morbidity and economic burden, novel ways of analyzing and predicting its progression are needed. One such computational method is the use of fluid-structure interaction (FSI) to analyze the interaction between the blood flow and artery/plaque domains. Coupled with in vivo imaging, this approach could be tailored to each patient, assisting in differentiating between stable and unstable plaques. We outline the three-dimensional reconstruction process, making use of intravascular Optical Coherence Tomography (OCT) and invasive coronary angiography (ICA). The extraction of boundary conditions for the simulation, including replicating the three-dimensional motion of the artery, is discussed before the setup and analysis is conducted in a commercial finite element solver. The procedure for describing the highly nonlinear hyperelastic properties of the artery wall and the pulsatile blood velocity/pressure is outlined along with setting up the system coupling between the two domains. We demonstrate the procedure by analyzing a non-culprit, mildly stenotic, lipid-rich plaque in a patient following myocardial infarction. Established and emerging markers related to atherosclerotic plaque progression, such as wall shear stress and local normalized helicity, respectively, are discussed and related to the structural response in the artery wall and plaque. Finally, we translate the results to potential clinical relevance, discuss limitations, and outline areas for further development. The method described in this paper shows promise for aiding in the determination of sites at risk of atherosclerotic progression and, hence, could assist in managing the significant death, morbidity, and economic burden of atherosclerosis.

There is a need to determine which atherosclerotic lesions will progress in the coronary vasculature to guide intervention before myocardial infarction occurs. This article outlines the biomechanical modeling of arteries from Optical Coherence Tomography using fluid-structure interaction techniques in a commercial finite element solver to help predict this progression.

In this paper, we present a complete workflow for the biomechanical analysis of atherosclerotic plaque in the coronary vasculature. With atherosclerosis ...

Preclinical Evaluation of Coronary Artery Stents

Coronary artery disease is a major contributor to morbidity and mortality worldwide. While lifestyle changes and medication are the cornerstones of treatment, coronary artery balloon angioplasty and stenting are routinely performed on patients with acute coronary syndromes and chronic coronary artery disease who remain symptomatic with optical medical treatment. Several generations of coronary stents have been developed over recent decades. Balloon angioplasty and stenting are supported by the use of pharmaceutical agents applied onto balloons and the stent surface, either to advance the healing properties of the artery post-intervention or to prevent the formation of restenosis. New devices need to be rigorously tested for safety and efficacy before acceptance into clinical practice; thus, there is a continuing need for reliable and reproducible preclinical methods of stent evaluation. We describe here a pig coronary artery model as well as an atherosclerotic rabbit model for coronary artery stent research and describe basic steps in intravascular imaging and stent histology.

New coronary artery stent designs and materials must be tested before clinical use in relevant preclinical models. Here we describe an atherosclerotic rabbit aorta model and a pig coronary artery model for stent research with in vivo and histological analyses.

Coronary artery disease is a major contributor to morbidity and mortality worldwide. While lifestyle changes and medication are the cornerstones of ...

Experimental Investigation of Secondary Flow Structures Downstream of a Model Type IV Stent Failure in a 180° Curved Artery Test Section

Summary

Explore More Videos

Chapters in this video

Monitoring the Wall Mechanics During Stent Deployment in a Vessel

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Imaging In-Stent Restenosis: An Inexpensive, Reliable, and Rapid Preclinical Model

Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention

4D Printed Bifurcated Stents with Kirigami-Inspired Structures

In vitro Assessment of Aortic Regurgitation Using Four-Dimensional Flow Magnetic Resonance Imaging

Particle Image Velocimetry Investigation of Hemodynamics via Aortic Phantom

Intravascular Ultrasound Image-Based Finite Element Modeling Approach for Quantifying In Vivo Mechanical Properties of Human Coronary Artery

Optical Coherence Tomography Based Biomechanical Fluid-Structure Interaction Analysis of Coronary Atherosclerosis Progression

Preclinical Evaluation of Coronary Artery Stents