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Irqsusi M, Rodepeter FR, Günther M, Kirschbaum A, Vogt S. Matrix metalloproteinases and their tissue inhibitors as indicators of aortic aneurysm and dissection development in extracellular matrix remodeling. World J Exp Med 2025; 15:100166. [DOI: 10.5493/wjem.v15.i2.100166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/04/2025] [Accepted: 01/15/2025] [Indexed: 04/16/2025] Open
Abstract
Aneurysms and dissections represent some of the most serious cardiovascular diseases. The prevailing theory posits that mechanical overloading of the vessel wall is the underlying cause. Inspired by Barkhordarian et al, the authors present matrix metalloproteinases (MMPs) and their inhibitors in immunohistological analyses as contributing factors in the pathophysiology of aortic aneurysms (AA). Data analysis of MMP-1, MMP-9, tissue inhibitors of metalloproteinases (TIMPs), including TIMP-1 and TIMP-2 expression reveals a varied distribution between the adventitia and media and a non-uniform expression of the investigated markers. These elements, as key components of the extracellular matrix (ECM), indicate that the formation of AA is not solely driven by endoluminal pressure loading of the aortic wall. Instead, degenerative processes within ECM elements contribute significantly. Importantly, AA do not necessarily imply dissection. Tissue destruction, allowing blood flow entry, arises from reduced oxygen supply to the media, primarily due to incomplete capillarization or neocapillarization.
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Affiliation(s)
- Marc Irqsusi
- Department of Heart Surgery, Universitätsklinikum Marburg and Gießen GmbH, Marburg 35043, Hesse, Germany
| | - Fiona R Rodepeter
- Institute of Pathology, Philipps-University Marburg, Marburg 35043, Hesse, Germany
| | - Madeline Günther
- Department of Heart Surgery, Cardiovascular Research Laboratory, Philipps-University Marburg, Marburg 35043, Hesse, Germany
| | - Andreas Kirschbaum
- Department of Visceral Surgery, University Hospital Giessen and Marburg GmbH, Marburg 35043, Hesse, Germany
| | - Sebastian Vogt
- Department of Heart Surgery, Philipps-University Marburg, Marburg 35043, Hesse, Germany
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Parikh S, Wehrens A, Giudici A, Ganizada B, Saraber P, Schurgers L, Debeij G, Natour E, Maessen J, Huberts W, Delhaas T, Reesink K, Bidar E. Interpretation of intra-operative strain differences in ascending thoracic aortic repair patients. J Biomech 2025; 179:112447. [PMID: 39644801 DOI: 10.1016/j.jbiomech.2024.112447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 11/10/2024] [Accepted: 11/28/2024] [Indexed: 12/09/2024]
Abstract
Local biaxial deformation plays a pivotal role in evaluating the tissue state of the ascending aorta and in driving intramural cell-mediated tissue remodeling. Unfortunately, the absence of anatomical markers on the ascending aorta presents challenges in capturing deformation. Utilizing our established intra-operative biaxial strain measurement method, we delineated local biaxial deformation characteristics in patients undergoing aortic valve replacement and coronary artery bypass graft surgery recipients (n = 20), and Aortic Repair surgery patients (n = 47). Expectedly, mean circumferential strains positively correlated with pulse pressure and negatively correlated with age and diameter. A new observation was that the mean axial strains exhibited the same trend as the mean circumferential strains when correlated with pulse pressure, age and diameter. Interestingly, on analyzing local biaxial strains, our findings revealed higher circumferential strains (by 1 %) proximal to the heart compared to distal regions across the cohorts and within each patient cohort. Furthermore, no discernible regional strain distinctions were noted between the medial and lateral sides of the ascending aorta for the entire patient population and individual cohorts. Patients undergoing Aortic Repair surgery indicated lower strains (ranging from 1 to 3 %) as compared to the other cohort. Our approach holds the potential to establish a foundational framework for the integrated examination of the mechanical and biological conditions and their role in ascending aortic aneurysm development.
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Affiliation(s)
- Shaiv Parikh
- Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
| | - Anne Wehrens
- Department of Cardiothoracic Surgery, CARIM School for Cardiovascular Diseases, Heart & Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
| | - Alessandro Giudici
- Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
| | - Berta Ganizada
- Department of Cardiothoracic Surgery, CARIM School for Cardiovascular Diseases, Heart & Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands; Department of Biochemistry, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
| | - Pepijn Saraber
- Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands; Department of Biochemistry, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
| | - Leon Schurgers
- Department of Biochemistry, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
| | - Gijs Debeij
- Department of Cardiothoracic Surgery, CARIM School for Cardiovascular Diseases, Heart & Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
| | - Ehsan Natour
- Department of Cardiothoracic Surgery, CARIM School for Cardiovascular Diseases, Heart & Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
| | - Jos Maessen
- Department of Cardiothoracic Surgery, CARIM School for Cardiovascular Diseases, Heart & Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
| | - Wouter Huberts
- Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands; Department of Biomedical Engineering, Cardiovascular Biomechanics, Eindhoven University of Technology, Eindhoven, The Netherlands.
| | - Tammo Delhaas
- Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
| | - Koen Reesink
- Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
| | - Elham Bidar
- Department of Cardiothoracic Surgery, CARIM School for Cardiovascular Diseases, Heart & Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
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Giudici A, Szafron JM, Ramachandra AB, Spronck B. Instability in Computational Models of Vascular Smooth Muscle Cell Contraction. Ann Biomed Eng 2024; 52:2403-2416. [PMID: 38949730 PMCID: PMC11329416 DOI: 10.1007/s10439-024-03532-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 04/30/2024] [Indexed: 07/02/2024]
Abstract
PURPOSE Through their contractile and synthetic capacity, vascular smooth muscle cells (VSMCs) can regulate the stiffness and resistance of the circulation. To model the contraction of blood vessels, an active stress component can be added to the (passive) Cauchy stress tensor. Different constitutive formulations have been proposed to describe this active stress component. Notably, however, measuring biomechanical behaviour of contracted blood vessels ex vivo presents several experimental challenges, which complicate the acquisition of comprehensive datasets to inform complex active stress models. In this work, we examine formulations for use with limited experimental contraction data as well as those developed to capture more comprehensive datasets. METHODS First, we prove analytically that a subset of constitutive active stress formulations exhibits unstable behaviours (i.e., a non-unique diameter solution for a given pressure) in certain parameter ranges, particularly for large contractile deformations. Second, using experimental literature data, we present two case studies where these formulations are used to capture the contractile response of VSMCs in the presence of (1) limited and (2) extensive contraction data. RESULTS We show how limited contraction data complicates selecting an appropriate active stress model for vascular applications, potentially resulting in unrealistic modelled behaviours. CONCLUSION Our data provide a useful reference for selecting an active stress model which balances the trade-off between accuracy and available biomechanical information. Whilst complex physiologically motivated models' superior accuracy is recommended whenever active biomechanics can be extensively characterised experimentally, a constant 2nd Piola-Kirchhoff active stress model balances well accuracy and applicability with sparse contractile data.
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Affiliation(s)
- Alessandro Giudici
- Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 40, Room C5.578A, Maastricht, 6229 ER, The Netherlands
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
| | - Jason M Szafron
- Department of Pediatrics, Stanford University, Stanford, CA, USA
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | | | - Bart Spronck
- Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 40, Room C5.578A, Maastricht, 6229 ER, The Netherlands.
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
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Irqsusi M, Dong LA, Rodepeter FR, Ramzan R, Talipov I, Ghazy T, Günther M, Vogt S, Rastan AJ. The Role of Matrix Metalloproteinases in Thoracic Aortic Disease: Are They Indicators for the Pathogenesis of Dissections? Biomedicines 2024; 12:619. [PMID: 38540232 PMCID: PMC10967891 DOI: 10.3390/biomedicines12030619] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/26/2024] [Accepted: 03/06/2024] [Indexed: 04/16/2025] Open
Abstract
The pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients who had coronary heart disease served as "healthy controls". All patients underwent the necessary surgical procedure according to the diagnosed aortic disease in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1 and MMP9 and TIMP1 and TIMP2 as well. Vascularization was monitored by a CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found the smallest changes in the intima area at all. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In the case of arteriosclerotic changes, intima had a capillarization, but not in the media. An opposite pattern was found in the dissected aortas. There are differences in the vascularization between the aneurysm and dissection and the different layers, respectively. A different remodeling process of the ECM in comparison to the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, disturbed nutrition, and dysfunctional vasa vasorum remodeling must be assumed as causes of dissection.
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Geronzi L, Bel-Brunon A, Martinez A, Rochette M, Sensale M, Bouchot O, Lalande A, Lin S, Valentini PP, Biancolini ME. Calibration of the Mechanical Boundary Conditions for a Patient-Specific Thoracic Aorta Model Including the Heart Motion Effect. IEEE Trans Biomed Eng 2023; 70:3248-3259. [PMID: 37390004 DOI: 10.1109/tbme.2023.3287680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2023]
Abstract
OBJECTIVE We propose a procedure for calibrating 4 parameters governing the mechanical boundary conditions (BCs) of a thoracic aorta (TA) model derived from one patient with ascending aortic aneurysm. The BCs reproduce the visco-elastic structural support provided by the soft tissue and the spine and allow for the inclusion of the heart motion effect. METHODS We first segment the TA from magnetic resonance imaging (MRI) angiography and derive the heart motion by tracking the aortic annulus from cine-MRI. A rigid-wall fluid-dynamic simulation is performed to derive the time-varying wall pressure field. We build the finite element model considering patient-specific material properties and imposing the derived pressure field and the motion at the annulus boundary. The calibration, which involves the zero-pressure state computation, is based on purely structural simulations. After obtaining the vessel boundaries from the cine-MRI sequences, an iterative procedure is performed to minimize the distance between them and the corresponding boundaries derived from the deformed structural model. A strongly-coupled fluid-structure interaction (FSI) analysis is finally performed with the tuned parameters and compared to the purely structural simulation. RESULTS AND CONCLUSION The calibration with structural simulations allows to reduce maximum and mean distances between image-derived and simulation-derived boundaries from 8.64 mm to 6.37 mm and from 2.24 mm to 1.83 mm, respectively. The maximum root mean square error between the deformed structural and FSI surface meshes is 0.19 mm. This procedure may prove crucial for increasing the model fidelity in replicating the real aortic root kinematics.
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Hegner A, Cebull HL, Gámez AJ, Blase C, Goergen CJ, Wittek A. Biomechanical characterization of tissue types in murine dissecting aneurysms based on histology and 4D ultrasound-derived strain. Biomech Model Mechanobiol 2023; 22:1773-1788. [PMID: 37707685 PMCID: PMC10511389 DOI: 10.1007/s10237-023-01759-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 07/26/2023] [Indexed: 09/15/2023]
Abstract
Abdominal aortic aneurysm disease is the local enlargement of the aorta, typically in the infrarenal section, causing up to 200,000 deaths/year. In vivo information to characterize the individual elastic properties of the aneurysm wall in terms of rupture risk is lacking. We used a method that combines 4D ultrasound and direct deformation estimation to compute in vivo 3D Green-Lagrange strain in murine angiotensin II-induced dissecting aortic aneurysms, a commonly used mouse model. After euthanasia, histological staining of cross-sectional sections along the aorta was performed in areas where in vivo strains had previously been measured. The histological sections were segmented into intact and fragmented elastin, thrombus with and without red blood cells, and outer vessel wall including the adventitia. Meshes were then created from the individual contours based on the histological segmentations. The isolated contours of the outer wall and lumen from both imaging modalities were registered individually using a coherent point drift algorithm. 2D finite element models were generated from the meshes, and the displacements from the registration were used as displacement boundaries of the lumen and wall contours. Based on the resulting deformed contours, the strains recorded were grouped according to segmented tissue regions. Strains were highest in areas containing intact elastin without thrombus attachment. Strains in areas with intact elastin and thrombus attachment, as well as areas with disrupted elastin, were significantly lower. Strains in thrombus regions with red blood cells were significantly higher compared to thrombus regions without. We then compared this analysis to statistical distribution indices and found that the results of each aligned, elucidating the relationship between vessel strain and structural changes. This work demonstrates the possibility of advancing in vivo assessments to a microstructural level ultimately improving patient outcomes.
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Affiliation(s)
- Achim Hegner
- Personalized Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am Main, Germany
- Department of Mechanical Engineering and Industrial Design, School of Engineering, University of Cadiz, Cadiz, Spain
| | - Hannah L. Cebull
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, USA
- Department of Radiology and Imaging Sciences, Emory University, Atlanta, USA
| | - Antonio J. Gámez
- Department of Mechanical Engineering and Industrial Design, School of Engineering, University of Cadiz, Cadiz, Spain
| | - Christopher Blase
- Personalized Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am Main, Germany
- Cell and Vascular Mechanics, Goethe University, Frankfurt am Main, Germany
| | - Craig J. Goergen
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, USA
| | - Andreas Wittek
- Personalized Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am Main, Germany
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Aggarwal A, Mortensen P, Hao J, Kaczmarczyk Ł, Cheung AT, Al Ghofaily L, Gorman RC, Desai ND, Bavaria JE, Pouch AM. Strain estimation in aortic roots from 4D echocardiographic images using medial modeling and deformable registration. Med Image Anal 2023; 87:102804. [PMID: 37060701 PMCID: PMC10358753 DOI: 10.1016/j.media.2023.102804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 01/30/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023]
Abstract
Even though the central role of mechanics in the cardiovascular system is widely recognized, estimating mechanical deformation and strains in-vivo remains an ongoing practical challenge. Herein, we present a semi-automated framework to estimate strains from four-dimensional (4D) echocardiographic images and apply it to the aortic roots of patients with normal trileaflet aortic valves (TAV) and congenital bicuspid aortic valves (BAV). The method is based on fully nonlinear shell-based kinematics, which divides the strains into in-plane (shear and dilatational) and out-of-plane components. The results indicate that, even for size-matched non-aneurysmal aortic roots, BAV patients experience larger regional shear strains in their aortic roots. This elevated strains might be a contributing factor to the higher risk of aneurysm development in BAV patients. The proposed framework is openly available and applicable to any tubular structures.
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Affiliation(s)
- Ankush Aggarwal
- Glasgow Computational Engineering Centre, James Watt School of Engineering, University of Glasgow, Glasgow, G12 8LT, Scotland, United Kingdom
| | - Peter Mortensen
- Glasgow Computational Engineering Centre, James Watt School of Engineering, University of Glasgow, Glasgow, G12 8LT, Scotland, United Kingdom
| | - Jilei Hao
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Łukasz Kaczmarczyk
- Glasgow Computational Engineering Centre, James Watt School of Engineering, University of Glasgow, Glasgow, G12 8LT, Scotland, United Kingdom
| | - Albert T Cheung
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA
| | - Lourdes Al Ghofaily
- Department of Anesthesiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Robert C Gorman
- Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Nimesh D Desai
- Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Joseph E Bavaria
- Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Alison M Pouch
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
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Giudici A, Spronck B, Wilkinson IB, Khir AW. Tri-layered constitutive modelling unveils functional differences between the pig ascending and lower thoracic aorta. J Mech Behav Biomed Mater 2023; 141:105752. [PMID: 36893688 DOI: 10.1016/j.jmbbm.2023.105752] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 02/22/2023] [Accepted: 03/01/2023] [Indexed: 03/05/2023]
Abstract
The arterial wall's tri-layered macroscopic and layer-specific microscopic structure determine its mechanical properties, which vary at different arterial locations. Combining layer-specific mechanical data and tri-layered modelling, this study aimed to characterise functional differences between the pig ascending (AA) and lower thoracic aorta (LTA). AA and LTA segments were obtained for n=9 pigs. For each location, circumferentially and axially oriented intact wall and isolated layer strips were tested uniaxially and the layer-specific mechanical response modelled using a hyperelastic strain energy function. Then, layer-specific constitutive relations and intact wall mechanical data were combined to develop a tri-layered model of an AA and LTA cylindrical vessel, accounting for the layer-specific residual stresses. AA and LTA behaviours were then characterised for in vivo pressure ranges while stretched axially to in vivo length. The media dominated the AA response, bearing>2/3 of the circumferential load both at physiological (100 mmHg) and hypertensive pressures (160 mmHg). The LTA media bore most of the circumferential load at physiological pressure only (57±7% at 100 mmHg), while adventitia and media load bearings were comparable at 160 mmHg. Furthermore, increased axial elongation affected the media/adventitia load-bearing only at the LTA. The pig AA and LTA presented strong functional differences, likely reflecting their different roles in the circulation. The media-dominated compliant and anisotropic AA stores large amounts of elastic energy in response to both circumferential and axial deformations, which maximises diastolic recoiling function. This function is reduced at the LTA, where the adventitia shields the artery against supra-physiological circumferential and axial loads.
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Affiliation(s)
- A Giudici
- Brunel Institute for Bioengineering, Brunel University London, Kingston Lane, Uxbridge, UB8 3PH, United Kingdom; Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Universiteitssingel 40, Maastricht, 6229 ER, the Netherlands
| | - B Spronck
- Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Universiteitssingel 40, Maastricht, 6229 ER, the Netherlands; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, Sydney, NSW, 2109, Australia
| | - I B Wilkinson
- Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Hills Road, Cambridge, CB2 0QO, United Kingdom
| | - A W Khir
- Brunel Institute for Bioengineering, Brunel University London, Kingston Lane, Uxbridge, UB8 3PH, United Kingdom; Department of Engineering, Durham University, Durham, DH1 3LE, United Kingdom.
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Bracamonte JH, Wilson JS, Soares JS. Quantification of the heterogeneous effect of static and dynamic perivascular structures on patient-specific local aortic wall mechanics using inverse finite element modeling and DENSE MRI. J Biomech 2022; 138:111119. [PMID: 35576631 PMCID: PMC9536506 DOI: 10.1016/j.jbiomech.2022.111119] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 04/28/2022] [Accepted: 04/29/2022] [Indexed: 11/30/2022]
Abstract
Recent studies have highlighted the relevance of perivascular interactions on aortic wall mechanics. Most of the approaches assume static perivascular structures; however, the beating heart dynamically displaces the neighboring aorta. We develop a model to account for the effect of periaortic interactions due to static and dynamic structures by prescribing a moving elastic foundation boundary condition (EFBC) embedded into an inverse finite element algorithm using in vivo displacements from 2D displacement encoding with stimulated echoes (DENSE) MRI as target data. We applied this method at three different locations of interest, the distal aortic arch (DAA), descending thoracic aorta (DTA), and infrarenal abdominal aorta (IAA) for a total of 27 cases in healthy humans. The model reproduces the target diastole-to-systole deformation and bulk displacement of the aortic wall with median displacement errors below 0.5mm. The EFBC showed good agreement with the location of anatomical features and was consistent among individuals of similar characteristics. Results show that an energy source acting on the adventitia is required to reproduce the displacements measured at the vicinity of the heart, but not at the abdomen. The average adventitial load as a percentage of the luminal pulse-pressure was found to increase with age and to decrease along the descending aorta, from 61% at the DAA to 37% at the DTA, and 30% at the IAA. This approach offers a patient-specific method to estimate in vivo adventitial loads and aortic wall stiffness, which can bring a better understanding of normal and pathological in vivo aortic function.
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Affiliation(s)
- Johane H Bracamonte
- Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, Richmond, VA 23284, United States.
| | - John S Wilson
- Department of Biomedical Engineering & Pauley Heart Center, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284, United States.
| | - Joao S Soares
- Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, Richmond, VA 23284, United States.
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Golemati S, Cokkinos DD. Recent advances in vascular ultrasound imaging technology and their clinical implications. ULTRASONICS 2022; 119:106599. [PMID: 34624584 DOI: 10.1016/j.ultras.2021.106599] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 08/26/2021] [Accepted: 09/21/2021] [Indexed: 06/13/2023]
Abstract
In this paper recent advances in vascular ultrasound imaging technology are discussed, including three-dimensional ultrasound (3DUS), contrast-enhanced ultrasound (CEUS) and strain- (SE) and shear-wave-elastography (SWE). 3DUS imaging allows visualisation of the actual 3D anatomy and more recently of flow, and assessment of geometrical, morphological and mechanical features in the carotid artery and the aorta. CEUS involves the use of microbubble contrast agents to estimate sensitive blood flow and neovascularisation (formation of new microvessels). Recent developments include the implementation of computerised tools for automated analysis and quantification of CEUS images, and the possibility to measure blood flow velocity in the aorta. SE, which yields anatomical maps of tissue strain, is increasingly being used to investigate the vulnerability of the carotid plaque, but is also promising for the coronary artery and the aorta. SWE relies on the generation of a shear wave by remote acoustic palpation and its acquisition by ultrafast imaging, and is useful for measuring arterial stiffness. Such advances in vascular ultrasound technology, with appropriate validation in clinical trials, could positively change current management of patients with vascular disease, and improve stratification of cardiovascular risk.
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Affiliation(s)
- Spyretta Golemati
- Medical School, National and Kapodistrian University of Athens, Athens, Greece.
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Li T, Liu X, Sun H, Ning H, Yang J, Ma C. Assessment of the Global and Regional Circumferential Strain of Abdominal Aortic Aneurysm with Different Size by Speckle-Tracking Echocardiography. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:2619-2627. [PMID: 33555036 DOI: 10.1002/jum.15651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/05/2021] [Accepted: 01/20/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVES We aimed to use speckle-tracking echocardiography (STE) to quantify circumferential aortic strain of abdominal aortic aneurysms (AAA) with different size. METHODS A total of 87 AAA patients were included. The morphological variables, including aortic maximum diameter (MD), end systolic area (ESA), end diastolic area (EDA), and thickness and area of intraluminal thrombus (ILT), were measured by ultrasound. STE was applied to calculate circumferential strain (CS) at 6 equally divided segments of the aorta at MD. We evaluated the mean value of peak strain along the 6 segments as global circumferential strain (GCS). RESULTS Large AAA (≥5.5 cm) patients had higher MD, ESA, EDA, AAA length, ILT thickness, and area, but lower fractional area change, GCS, and segmental CSs than small AAA (<5.5 cm) subjects (all P < .05). Compared with AAA <4.5 cm group, AAA patients ≥4.5 cm possessed increased MD, ESA, EDA, AAA length, ILT thickness, and area, which results were also reflected in the comparison between AAA <6.5 and ≥6.5 cm group. In small AAA patients, GCS and regional strains in CS1, CS3, and CS5 segments were lower in AAA subjects ≥4.5 cm than those <4.5 cm (all P<.05). However, no significant differences in the GCS and regional CS between ≥6.5 and <6.5 cm group were found. Correlation analysis revealed a significant negative association of GCS with MD, ESA, and EDA, even after adjusting the potential confounding factors (all P < .05). CONCLUSIONS Our findings may yield insight into the structural strain characteristics of AAA wall with different size, which adds the benefit of using simple echocardiography-derived biomechanics to stratify AAA patients.
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Affiliation(s)
- Tan Li
- Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, China
| | - Xiaozheng Liu
- Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, China
| | - Haiyang Sun
- Department of Ultrasound, Shenyang Women's and Children's Hospital, Shenyang, China
| | - Hongxia Ning
- Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, China
| | - Jun Yang
- Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, China
| | - Chunyan Ma
- Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, China
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Kemper PPN, Mahmoudi S, Apostolakis IZ, Konofagou EE. Feasibility of Bilinear Mechanical Characterization of the Abdominal Aorta in a Hypertensive Mouse Model. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:3480-3490. [PMID: 34507874 PMCID: PMC8693438 DOI: 10.1016/j.ultrasmedbio.2021.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 07/28/2021] [Accepted: 08/01/2021] [Indexed: 05/19/2023]
Abstract
A change in elastin and collagen content is indicative of damage caused by hypertension, which changes the non-linear behavior of the vessel wall. This study was aimed at investigating the feasibility of monitoring the non-linear material behavior in an angiotensin II hypertensive mice model. Aortas from 13 hypertensive mice were imaged with pulse wave imaging (PWI) over 4 wk using a 40-MHz linear array. The pulse wave velocity was estimated using two wave features: (i) the maximum axial acceleration of the foot (PWVdia) and (ii) the maximum axial acceleration of the dicrotic notch (PWVend-sys). The Bramwell-Hill equation was used to derive the compliance at diastolic and end-systolic pressure. This study determined the potential of PWI in a hypertensive mouse model to image and quantify the non-linear material behavior in vivo. End-systolic compliance could differentiate between the sham and angiotensin II groups, whereas diastolic compliance could not, indicating that PWI can detect early collagen-dominated remodeling.
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Affiliation(s)
- Paul P N Kemper
- Ultrasound and Elasticity Imaging Laboratory, Department of Biomedical Engineering, Columbia University, New York, New York, USA.
| | - Salah Mahmoudi
- Ultrasound and Elasticity Imaging Laboratory, Department of Biomedical Engineering, Columbia University, New York, New York, USA
| | - Iason Zacharias Apostolakis
- Ultrasound and Elasticity Imaging Laboratory, Department of Biomedical Engineering, Columbia University, New York, New York, USA
| | - Elisa E Konofagou
- Ultrasound and Elasticity Imaging Laboratory, Department of Biomedical Engineering, Columbia University, New York, New York, USA; Department of Radiology, Columbia University, New York, New York, USA
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13
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Derwich W, Wiedemann A, Wittek A, Filmann N, Blase C, Schmitz-Rixen T. Intra- and Interobserver Variability of 4D Ultrasound Examination of the Infrarenal Aorta. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:2391-2402. [PMID: 33452839 DOI: 10.1002/jum.15622] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 12/01/2020] [Accepted: 12/24/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVES The four-dimensional ultrasound (4D-US) enables imaging of the aortic segment and simultaneous determination of the wall expansion. The method shows a high spatial and temporal resolution, but its in vivo reliability is so far unknown for low-measure values. The present study determines the intraobserver repeatability and interobserver reproducibility of 4D-US in the atherosclerotic and non-atherosclerotic infrarenal aorta. METHODS In all, 22 patients with non-aneurysmal aorta were examined by an experienced examiner and a medical student. After registration of 4D images, both the examiners marked the aortic wall manually before the commercially implemented speckle tracking algorithm was applied. The cyclic changes of the aortic diameter and circumferential strain were determined with the help of custom-made software. The reliability of 4D-US was tested by the intraclass correlation coefficient (ICC). RESULTS The 4D-US measurements showed very good reliability for the maximum aortic diameter and the circumferential strain for all patients and for the non-atherosclerotic aortae (ICC >0.7), but low reliability for circumferential strain in calcified aortae (ICC = 0.29). The observer- and masking-related variances for both maximum diameter and circumferential strain were close to zero. CONCLUSIONS Despite the low-measured values, the high spatial and temporal resolution of the 4D-US enables a reliable evaluation of cyclic diameter changes and circumferential strain in non-aneurysmal aortae independent from the observer experience but with some limitations for calcified aortae. The 4D-US opens up a new perspective with regard to noninvasive, in vivo assessment of kinematic properties of the vessel wall in the abdominal aorta.
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Affiliation(s)
- Wojciech Derwich
- Department of Vascular and Endovascular Surgery, University Hospital Frankfurt Goethe University, Frankfurt am Main, Germany
| | - Antonia Wiedemann
- Department of Vascular and Endovascular Surgery, University Hospital Frankfurt Goethe University, Frankfurt am Main, Germany
| | - Andreas Wittek
- Personalised Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am Main, Germany
- Department of Mechanical Engineering, University of Siegen, Siegen, Germany
| | - Natalie Filmann
- Institute for Biostatistics and Mathematical Modeling, Goethe University, Frankfurt am Main, Germany
| | - Christopher Blase
- Personalised Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am Main, Germany
- Department of Biological Sciences, Goethe University, Frankfurt am Main, Germany
| | - Thomas Schmitz-Rixen
- Department of Vascular and Endovascular Surgery, University Hospital Frankfurt Goethe University, Frankfurt am Main, Germany
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14
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Dessalles CA, Ramón-Lozano C, Babataheri A, Barakat AI. Luminal flow actuation generates coupled shear and strain in a microvessel-on-chip. Biofabrication 2021; 14. [PMID: 34592728 DOI: 10.1088/1758-5090/ac2baa] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 09/30/2021] [Indexed: 12/12/2022]
Abstract
In the microvasculature, blood flow-derived forces are key regulators of vascular structure and function. Consequently, the development of hydrogel-based microvessel-on-chip systems that strive to mimic thein vivocellular organization and mechanical environment has received great attention in recent years. However, despite intensive efforts, current microvessel-on-chip systems suffer from several limitations, most notably failure to produce physiologically relevant wall strain levels. In this study, a novel microvessel-on-chip based on the templating technique and using luminal flow actuation to generate physiologically relevant levels of wall shear stress and circumferential stretch is presented. Normal forces induced by the luminal pressure compress the surrounding soft collagen hydrogel, dilate the channel, and create large circumferential strain. The fluid pressure gradient in the system drives flow forward and generates realistic pulsatile wall shear stresses. Rigorous characterization of the system reveals the crucial role played by the poroelastic behavior of the hydrogel in determining the magnitudes of the wall shear stress and strain. The experimental measurements are combined with an analytical model of flow in both the lumen and the porous hydrogel to provide an exceptionally versatile user manual for an application-based choice of parameters in microvessels-on-chip. This unique strategy of flow actuation adds a dimension to the capabilities of microvessel-on-chip systems and provides a more general framework for improving hydrogel-basedin vitroengineered platforms.
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Affiliation(s)
- Claire A Dessalles
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, 91120 Palaiseau, France
| | - Clara Ramón-Lozano
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, 91120 Palaiseau, France
| | - Avin Babataheri
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, 91120 Palaiseau, France
| | - Abdul I Barakat
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, 91120 Palaiseau, France
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15
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Tang M, Eliathamby D, Ouzounian M, Simmons CA, Chung JCY. Dependency of energy loss on strain rate, strain magnitude and preload: Towards development of a novel biomarker for aortic aneurysm dissection risk. J Mech Behav Biomed Mater 2021; 124:104736. [PMID: 34563811 DOI: 10.1016/j.jmbbm.2021.104736] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 06/12/2021] [Accepted: 07/26/2021] [Indexed: 01/15/2023]
Abstract
Dissection is the most common mode of failure for ascending aortic aneurysms. Currently, failure risk is assessed by measuring aortic diameter, which is insufficient as it misses many dissection patients. This motivated the search for a new biomarker that captures intrinsic tissue material properties related to failure. Energy loss is promising in this regard as it is correlated with microstructure degradation and failure of aneurysms. However, for energy loss to be used clinically, its dependency on in vivo loading conditions, which vary from patient-to-patient, must be determined. In this study, the sensitivity of energy loss to physiological strain rate, magnitude, and preload was examined. Energy loss was found to be relatively insensitive to loading conditions while maintaining a significant correlation with delamination strength as a surrogate for dissection except at low strains. These results can be used for clinical translation of in vivo measurements of energy loss to evaluate aortic dissection risk.
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Affiliation(s)
- Mingyi Tang
- Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, ON, Canada; Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada
| | - Daniella Eliathamby
- Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
| | - Maral Ouzounian
- Division of Cardiac Surgery, University Health Network, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Craig A Simmons
- Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, ON, Canada; Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
| | - Jennifer C-Y Chung
- Division of Cardiac Surgery, University Health Network, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada.
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16
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Dessalles CA, Leclech C, Castagnino A, Barakat AI. Integration of substrate- and flow-derived stresses in endothelial cell mechanobiology. Commun Biol 2021; 4:764. [PMID: 34155305 PMCID: PMC8217569 DOI: 10.1038/s42003-021-02285-w] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 06/02/2021] [Indexed: 02/05/2023] Open
Abstract
Endothelial cells (ECs) lining all blood vessels are subjected to large mechanical stresses that regulate their structure and function in health and disease. Here, we review EC responses to substrate-derived biophysical cues, namely topography, curvature, and stiffness, as well as to flow-derived stresses, notably shear stress, pressure, and tensile stresses. Because these mechanical cues in vivo are coupled and are exerted simultaneously on ECs, we also review the effects of multiple cues and describe burgeoning in vitro approaches for elucidating how ECs integrate and interpret various mechanical stimuli. We conclude by highlighting key open questions and upcoming challenges in the field of EC mechanobiology.
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Affiliation(s)
- Claire A Dessalles
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, Palaiseau, France
| | - Claire Leclech
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, Palaiseau, France
| | - Alessia Castagnino
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, Palaiseau, France
| | - Abdul I Barakat
- LadHyX, CNRS, Ecole polytechnique, Institut polytechnique de Paris, Palaiseau, France.
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17
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Intra-Operative Video-Based Measurement of Biaxial Strains of the Ascending Thoracic Aorta. Biomedicines 2021; 9:biomedicines9060670. [PMID: 34207976 PMCID: PMC8230589 DOI: 10.3390/biomedicines9060670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/31/2021] [Accepted: 06/08/2021] [Indexed: 11/17/2022] Open
Abstract
Local biaxial deformation measurements are essential for the in-depth investigation of tissue properties and remodeling of the ascending thoracic aorta, particularly in aneurysm formation. Current clinical imaging modalities pose limitations around the resolution and tracking of anatomical markers. We evaluated a new intra-operative video-based method to assess local biaxial strains of the ascending thoracic aorta. In 30 patients undergoing open-chest surgery, we obtained repeated biaxial strain measurements, at low- and high-pressure conditions. Precision was very acceptable, with coefficients of variation for biaxial strains remaining below 20%. With our four-marker arrangement, we were able to detect significant local differences in the longitudinal strain as well as in circumferential strain. Overall, the magnitude of strains we obtained (range: 0.02–0.05) was in line with previous reports using other modalities. The proposed method enables the assessment of local aortic biaxial strains and may enable new, clinically informed mechanistic studies using biomechanical modeling as well as mechanobiological profiling.
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18
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Johnston L, Allen R, Hall Barrientos P, Mason A, Kazakidi A. Hemodynamic Abnormalities in the Aorta of Turner Syndrome Girls. Front Cardiovasc Med 2021; 8:670841. [PMID: 34141729 PMCID: PMC8203817 DOI: 10.3389/fcvm.2021.670841] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/06/2021] [Indexed: 01/15/2023] Open
Abstract
Congenital abnormalities in girls and women with Turner syndrome (TS), alongside an underlying predisposition to obesity and hypertension, contribute to an increased risk of cardiovascular disease and ultimately reduced life expectancy. We observe that children with TS present a greater variance in aortic arch morphology than their healthy counterparts, and hypothesize that their hemodynamics is also different. In this study, computational fluid dynamic (CFD) simulations were performed for four TS girls, and three age-matched healthy girls, using patient-specific inlet boundary conditions, obtained from phase-contrast MRI data. The visualization of multidirectional blood flow revealed an increase in vortical flow in the arch, supra-aortic vessels, and descending aorta, and a correlation between the presence of aortic abnormalities and disturbed flow. Compared to the relatively homogeneous pattern of time-averaged wall shear stress (TAWSS) on the healthy aortae, a highly heterogeneous distribution with elevated TAWSS values was observed in the TS geometries. Visualization of further shear stress parameters, such as oscillatory shear index (OSI), normalized relative residence time (RRTn), and transverse WSS (transWSS), revealed dissimilar heterogeneity in the oscillatory and multidirectional nature of the aortic flow. Taking into account the young age of our TS cohort (average age 13 ± 2 years) and their obesity level (75% were obese or overweight), which is believed to accelerate the initiation and progression of endothelial dysfunction, these findings may be an indication of atherosclerotic disease manifesting earlier in life in TS patients. Age, obesity and aortic morphology may, therefore, play a key role in assessing cardiovascular risk in TS children.
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Affiliation(s)
- Lauren Johnston
- Department of Biomedical Engineering, University of Strathclyde, Glasgow, United Kingdom
| | - Ruth Allen
- Department of Radiology, Royal Hospital for Children, Glasgow, United Kingdom
| | | | - Avril Mason
- Department of Paediatric Endocrinology, Royal Hospital for Children, Queen Elizabeth University Hospital, Glasgow, United Kingdom
| | - Asimina Kazakidi
- Department of Biomedical Engineering, University of Strathclyde, Glasgow, United Kingdom
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19
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The Progress of Advanced Ultrasonography in Assessing Aortic Stiffness and the Application Discrepancy between Humans and Rodents. Diagnostics (Basel) 2021; 11:diagnostics11030454. [PMID: 33800855 PMCID: PMC8001300 DOI: 10.3390/diagnostics11030454] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 02/26/2021] [Accepted: 03/02/2021] [Indexed: 12/26/2022] Open
Abstract
Aortic stiffening is a fundamental pathological alteration of atherosclerosis and other various aging-associated vascular diseases, and it is also an independent risk factor of cardiovascular morbidity and mortality. Ultrasonography is a critical non-invasive method widely used in assessing aortic structure, function, and hemodynamics in humans, playing a crucial role in predicting the pathogenesis and adverse outcomes of vascular diseases. However, its applications in rodent models remain relatively limited, hindering the progress of the research. Here, we summarized the progress of the advanced ultrasonographic techniques applied in evaluating aortic stiffness. With multiple illustrative images, we mainly characterized various ultrasound techniques in assessing aortic stiffness based on the alterations of aortic structure, hemodynamics, and tissue motion. We also discussed the discrepancy of their applications in humans and rodents and explored the potential optimized strategies in the experimental research with animal models. This updated information would help to better understand the nature of ultrasound techniques and provide a valuable prospect for their applications in assessing aortic stiffness in basic science research, particularly with small animals.
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20
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Giudici A, Wilkinson IB, Khir AW. Review of the Techniques Used for Investigating the Role Elastin and Collagen Play in Arterial Wall Mechanics. IEEE Rev Biomed Eng 2021; 14:256-269. [PMID: 32746366 DOI: 10.1109/rbme.2020.3005448] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The arterial wall is characterised by a complex microstructure that impacts the mechanical properties of the vascular tissue. The main components consist of collagen and elastin fibres, proteoglycans, Vascular Smooth Muscle Cells (VSMCs) and ground matrix. While VSMCs play a key role in the active mechanical response of arteries, collagen and elastin determine the passive mechanics. Several experimental methods have been designed to investigate the role of these structural proteins in determining the passive mechanics of the arterial wall. Microscopy imaging of load-free or fixed samples provides useful information on the structure-function coupling of the vascular tissue, and mechanical testing provides information on the mechanical role of collagen and elastin networks. However, when these techniques are used separately, they fail to provide a full picture of the arterial micromechanics. More recently, advances in imaging techniques have allowed combining both methods, thus dynamically imaging the sample while loaded in a pseudo-physiological way, and overcoming the limitation of using either of the two methods separately. The present review aims at describing the techniques currently available to researchers for the investigation of the arterial wall micromechanics. This review also aims to elucidate the current understanding of arterial mechanics and identify some research gaps.
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21
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Liu M, Liang L, Sun W. A generic physics-informed neural network-based constitutive model for soft biological tissues. COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING 2020; 372:113402. [PMID: 34012180 PMCID: PMC8130895 DOI: 10.1016/j.cma.2020.113402] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
Constitutive modeling is a cornerstone for stress analysis of mechanical behaviors of biological soft tissues. Recently, it has been shown that machine learning (ML) techniques, trained by supervised learning, are powerful in building a direct linkage between input and output, which can be the strain and stress relation in constitutive modeling. In this study, we developed a novel generic physics-informed neural network material (NNMat) model which employs a hierarchical learning strategy by following the steps: (1) establishing constitutive laws to describe general characteristic behaviors of a class of materials; (2) determining constitutive parameters for an individual subject. A novel neural network structure was proposed which has two sets of parameters: (1) a class parameter set for characterizing the general elastic properties; and (2) a subject parameter set (three parameters) for describing individual material response. The trained NNMat model may be directly adopted for a different subject without re-training the class parameters, and only the subject parameters are considered as constitutive parameters. Skip connections are utilized in the neural network to facilitate hierarchical learning. A convexity constraint was imposed to the NNMat model to ensure that the constitutive model is physically relevant. The NNMat model was trained, cross-validated and tested using biaxial testing data of 63 ascending thoracic aortic aneurysm tissue samples, which was compared to expert-constructed models (Holzapfel-Gasser-Ogden, Gasser-Ogden-Holzapfel, and four-fiber families) using the same fitting and testing procedure. Our results demonstrated that the NNMat model has a significantly better performance in both fitting (R2 value of 0.9632 vs 0.9019, p=0.0053) and testing (R2 value of 0.9471 vs 0.8556, p=0.0203) than the Holzapfel-Gasser-Ogden model. The proposed NNMat model provides a convenient and general methodology for constitutive modeling.
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Affiliation(s)
- Minliang Liu
- Tissue Mechanics Laboratory, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States of America
| | - Liang Liang
- Department of Computer Science, University of Miami, Coral Gables, FL, United States of America
| | - Wei Sun
- Tissue Mechanics Laboratory, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States of America
- Correspondence to: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Technology Enterprise Park, Room 206 387 Technology Circle, Atlanta GA 30313-2412, United States of America. (W. Sun)
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22
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Deciphering ascending thoracic aortic aneurysm hemodynamics in relation to biomechanical properties. Med Eng Phys 2020; 82:119-129. [DOI: 10.1016/j.medengphy.2020.07.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 06/19/2020] [Accepted: 07/09/2020] [Indexed: 12/20/2022]
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Gode S, Akinci O, Ustunısık CT, Sen O, Kadirogulları E, Aksu T, Ersoy B, Gurbak I, Duman ZM, Erentug V. The role of the angle of the ascending aortic curvature on the development of type A aortic dissection: ascending aortic angulation and dissection. Interact Cardiovasc Thorac Surg 2020; 29:615-620. [PMID: 31203369 DOI: 10.1093/icvts/ivz144] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 04/29/2019] [Accepted: 05/14/2019] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES Type A aortic dissection (TAD), which consists of an intimal tear in the aorta, necessitates emergency surgery. Various risk factors related to aortic dissection have been defined in the literature. According to our hypothesis, a narrower angle of ascending aortic curvature (AAAC) may be an additional risk factor in relation to aortic dissection due to the increased force applied to the aortic wall. METHODS Patients undergoing ascending aortic surgery due to an ascending aortic aneurysm (AsAA) (n = 105) and patients undergoing such surgery because of the occurrence of TAD (n = 101) were enrolled in this study. The AAAC was measured using Cobb's method; the measurements were made on all patients by just 1 cardiovascular radiologist using 3-dimensional computerized tomographic imaging. This measurement was made indirectly by using the aortic valve and brachiocephalic artery to avoid obtaining misleading data as a result of distortions due to dissection. A statistical comparison was also performed relating the traditional risk factors for TAD to other clinical and echocardiographic parameters: the diameter of the ascending aorta and the AAAC. RESULTS The AAAC was found to be narrower statistically in the TAD group (α = 76.2° ± 17.5°) than it was in the AsAA group (α = 92.9° ± 13°) (P < 0.001). Furthermore, mean ascending aortic diameter (P = 0.019), the presence of a bicuspid aorta (P = 0.007) and aortic valve stenosis (P = 0.005) were higher in the AsAA group. According to multivariable analyses, a narrower AAAC is a significant predictor for the development of TAD (odds ratio 0.93, 95% confidence interval 0.91-0.95; P < 0.001). Overall hospital mortality from various causes including stroke, myocardial infarction, bleeding or renal failure was 13% in the TAD group and 7% in the AsAA group. CONCLUSIONS According to this study, the AAAC was significantly smaller in aortic dissection patients than in aortic aneurysm patients. This may be related to higher shear stress and elevated pressure on the ascending aorta in patients with a narrower AAAC. Thus, a narrower AAAC may be an additional risk factor in the development of TAD. Therefore, we may need to be more careful in terms of looking for the development of aortic dissection in patients with narrower AAAC.
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Affiliation(s)
- Safa Gode
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Okan Akinci
- Department of Radiology, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Cigdem Tel Ustunısık
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Onur Sen
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Ersin Kadirogulları
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Timucin Aksu
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Burak Ersoy
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Ismail Gurbak
- Department of Cardiology, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Zihni Mert Duman
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
| | - Vedat Erentug
- Department of Cardiovascular Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
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24
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Wilson JS, Taylor WR, Oshinski J. Assessment of the regional distribution of normalized circumferential strain in the thoracic and abdominal aorta using DENSE cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2019; 21:59. [PMID: 31522679 PMCID: PMC6745772 DOI: 10.1186/s12968-019-0565-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 07/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Displacement Encoding with Stimulated Echoes (DENSE) cardiovascular magnetic resonance (CMR) of the aortic wall offers the potential to improve patient-specific diagnostics and prognostics of diverse aortopathies by quantifying regionally heterogeneous aortic wall strain in vivo. However, before regional mapping of strain can be used to clinically assess aortic pathology, an evaluation of the natural variation of normal regional aortic kinematics is required. METHOD Aortic spiral cine DENSE CMR was performed at 3 T in 30 healthy adult subjects (range 18 to 65 years) at one or more axial locations that are at high risk for aortic aneurysm or dissection: the infrarenal abdominal aorta (IAA, n = 11), mid-descending thoracic aorta (DTA, n = 17), and/or distal aortic arch (DAA, n = 11). After implementing custom noise-reduction techniques, regional circumferential Green strain of the aortic wall was calculated across 16 sectors around the aortic circumference at each location and normalized by the mean circumferential strain for comparison between individuals. RESULTS The distribution of normalized circumferential strain (NCS) was heterogeneous for all locations evaluated. Despite large differences in mean strain between subjects, comparisons of NCS revealed consistent patterns of strain distribution for similar groupings of patients by axial location, age, and/or mean displacement angle. NCS at local systole was greatest in the lateral/posterolateral walls in the IAAs (1.47 ± 0.27), medial wall in anteriorly displacing DTAs (1.28 ± 0.20), lateral wall in posteriorly displacing DTAs (1.29 ± 0.29), superior curvature in DAAs < 50 years-old (1.93 ± 0.22), and medial wall in DAAs > 50 years (2.29 ± 0.58). The distribution of strain was strongly influenced by the location of the vertebra and other surrounding structures unique to each location. CONCLUSIONS Regional in vivo circumferential strain in the adult aorta is unique to each axial location and heterogeneous around its circumference, but can be grouped into consistent patterns defined by basic patient-specific metrics following normalization. The heterogeneous strain distributions unique to each group may be due to local peri-aortic constraints (particularly at the aorto-vertebral interface), heterogeneous material properties, and/or heterogeneous flow patterns. These results must be carefully considered in future studies seeking to clinically interpret or computationally model patient-specific aortic kinematics.
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Affiliation(s)
- John S. Wilson
- Department of Biomedical Engineering and Pauley Heart Center, Virginia Commonwealth University, P.O. Box 980335, Richmond, VA USA
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA USA
| | - W. Robert Taylor
- Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA USA
- Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA USA
- Division of Cardiology, Department of Medicine, Atlanta VA Medical Center, Decatur, GA USA
| | - John Oshinski
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA USA
- Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA USA
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Liu M, Liang L, Sulejmani F, Lou X, Iannucci G, Chen E, Leshnower B, Sun W. Identification of in vivo nonlinear anisotropic mechanical properties of ascending thoracic aortic aneurysm from patient-specific CT scans. Sci Rep 2019; 9:12983. [PMID: 31506507 PMCID: PMC6737100 DOI: 10.1038/s41598-019-49438-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 08/24/2019] [Indexed: 12/15/2022] Open
Abstract
Accurate identification of in vivo nonlinear, anisotropic mechanical properties of the aortic wall of individual patients remains to be one of the critical challenges in the field of cardiovascular biomechanics. Since only the physiologically loaded states of the aorta are given from in vivo clinical images, inverse approaches, which take into account of the unloaded configuration, are needed for in vivo material parameter identification. Existing inverse methods are computationally expensive, which take days to weeks to complete for a single patient, inhibiting fast feedback for clinicians. Moreover, the current inverse methods have only been evaluated using synthetic data. In this study, we improved our recently developed multi-resolution direct search (MRDS) approach and the computation time cost was reduced to 1~2 hours. Using the improved MRDS approach, we estimated in vivo aortic tissue elastic properties of two ascending thoracic aortic aneurysm (ATAA) patients from pre-operative gated CT scans. For comparison, corresponding surgically-resected aortic wall tissue samples were obtained and subjected to planar biaxial tests. Relatively close matches were achieved for the in vivo-identified and ex vivo-fitted stress-stretch responses. It is hoped that further development of this inverse approach can enable an accurate identification of the in vivo material parameters from in vivo image data.
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Affiliation(s)
- Minliang Liu
- Tissue Mechanics Laboratory, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
| | - Liang Liang
- Tissue Mechanics Laboratory, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.,Department of Computer Science, University of Miami, Coral Gables, FL, USA
| | - Fatiesa Sulejmani
- Tissue Mechanics Laboratory, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
| | - Xiaoying Lou
- Tissue Mechanics Laboratory, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.,Emory University School of Medicine, Atlanta, GA, USA
| | - Glen Iannucci
- Emory University School of Medicine, Atlanta, GA, USA
| | - Edward Chen
- Emory University School of Medicine, Atlanta, GA, USA
| | | | - Wei Sun
- Tissue Mechanics Laboratory, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
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26
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Loosli C, Rupp S, Thamsen B, Rebholz M, Kress G, Meboldt M, Ermanni P. High-frequency operation of pulsatile ventricular assist devices: A computational study on circular and elliptically shaped pumps. Int J Artif Organs 2019; 42:725-734. [PMID: 31277562 DOI: 10.1177/0391398819857442] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Pulsatile positive displacement pumps as ventricular assist devices were gradually replaced by rotary devices due to their large volume and high adverse event rates. Nevertheless, pulsatile ventricular assist devices might be beneficial with regard to gastrointestinal bleeding and cardiac recovery. Therefore, aim of this study was to investigate the flow field in new pulsatile ventricular assist devices concepts with an increased pump frequency, which would allow lower stroke volumes to reduce the pump size. We developed a novel elliptically shaped pulsatile ventricular assist devices, which we compared to a design based on a circular shape. The pump size was adjusted to deliver similar flow rates at pump frequencies of 80, 160, and 240 bpm. Through a computational fluid dynamics study, we investigated flow patterns, residence times, and wall shear stresses for different frequencies and pump sizes. A pump size reduction by almost 50% is possible when using a threefold pump frequency. We show that flow patterns inside the circular pump are frequency dependent, while they remain similar for the elliptic pump. With slightly increased wall shear stresses for higher frequencies, maximum wall shear stresses on the pump housing are higher for the circular design (42.2 Pa vs 18.4 Pa). The calculated blood residence times within the pump decrease significantly with increasing pump rates. A smaller pump size leads to a slight increase of wall shear stresses and a significant improvement of residence times. Hence, high-frequency operation of pulsatile ventricular assist devices, especially in combination with an elliptical shape, might be a feasible mean to reduce the size, without any expectable disadvantages in terms of hemocompatibility.
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Affiliation(s)
- Christian Loosli
- Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering, ETH Zürich, Zürich, Switzerland
| | - Stephan Rupp
- Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering, ETH Zürich, Zürich, Switzerland
| | - Bente Thamsen
- Product Development Group Zurich, Department of Mechanical and Process Engineering, ETH Zürich, Zürich, Switzerland.,Pediatric Heart Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Mathias Rebholz
- Product Development Group Zurich, Department of Mechanical and Process Engineering, ETH Zürich, Zürich, Switzerland
| | - Gerald Kress
- Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering, ETH Zürich, Zürich, Switzerland
| | - Mirko Meboldt
- Product Development Group Zurich, Department of Mechanical and Process Engineering, ETH Zürich, Zürich, Switzerland
| | - Paolo Ermanni
- Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering, ETH Zürich, Zürich, Switzerland
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27
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Bernardi L, Giampietro C, Marina V, Genta M, Mazza E, Ferrari A. Adaptive reorientation of endothelial collectives in response to strain. Integr Biol (Camb) 2019; 10:527-538. [PMID: 30112523 DOI: 10.1039/c8ib00092a] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Mature epithelial monolayers share the ability to coherently respond to external mechanical stimuli. Tissue remodeling requires cell shape changes and coordinated movements. Human endothelia provide an exquisite example of such emerging collective activities. As part of their function in maintaining body homeostasis under variable hemodynamic loadings, endothelial ensembles must dynamically adapt to wall shear stress and cyclic deformation. While the alignment of several types of cells, including fibroblasts, osteoblasts and epithelial tissues, in response to various flow conditions or wall shear stress levels has been described in detail, less is known about collective endothelial remodeling under pure wall deformation. Here, using a custom-developed bioreactor, we exposed mature human endothelia to two distinct physiological levels of cyclic loading, generating overlapping gradients of strain. Endothelial cells remodeled depending on the level of imposed strain yielding local variations of cell density. In particular, a collective cell orientation orthogonal to the main direction of strain was observed at low levels of wall deformation, while cells reoriented parallel to the main direction of strain at high levels of wall deformation. The tissue adaptation depended on the establishment of mature adherens junctions, which were reinforced by the polarized recruitment of the adaptor protein vinculin. The pivotal role of cell-to-cell junctions was confirmed by the biochemical inhibition of vascular endothelial cadherin homotypic contacts, which impaired the collective remodeling. Together, our data establish wall deformation as an independent determinant of endothelial architecture with direct implications in vascular physiopathology.
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Affiliation(s)
- Laura Bernardi
- ETH Zurich, Institute for Mechanical Systems, 8092 Zürich, Switzerland.
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28
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Cosentino F, Agnese V, Raffa GM, Gentile G, Bellavia D, Zingales M, Pilato M, Pasta S. On the role of material properties in ascending thoracic aortic aneurysms. Comput Biol Med 2019; 109:70-78. [DOI: 10.1016/j.compbiomed.2019.04.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 04/20/2019] [Accepted: 04/20/2019] [Indexed: 12/31/2022]
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29
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Liu M, Liang L, Sun W. Estimation of in vivo constitutive parameters of the aortic wall using a machine learning approach. COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING 2019; 347:201-217. [PMID: 31160830 PMCID: PMC6544444 DOI: 10.1016/j.cma.2018.12.030] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
The patient-specific biomechanical analysis of the aorta requires the quantification of the in vivo mechanical properties of individual patients. Current inverse approaches have attempted to estimate the nonlinear, anisotropic material parameters from in vivo image data using certain optimization schemes. However, since such inverse methods are dependent on iterative nonlinear optimization, these methods are highly computation-intensive. A potential paradigm-changing solution to the bottleneck associated with patient-specific computational modeling is to incorporate machine learning (ML) algorithms to expedite the procedure of in vivo material parameter identification. In this paper, we developed an ML-based approach to estimate the material parameters from three-dimensional aorta geometries obtained at two different blood pressure (i.e., systolic and diastolic) levels. The nonlinear relationship between the two loaded shapes and the constitutive parameters are established by an ML-model, which was trained and tested using finite element (FE) simulation datasets. Cross-validations were used to adjust the ML-model structure on a training/validation dataset. The accuracy of the ML-model was examined using a testing dataset.
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Affiliation(s)
- Minliang Liu
- Tissue Mechanics Laboratory The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA
| | - Liang Liang
- Tissue Mechanics Laboratory The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA
| | - Wei Sun
- Tissue Mechanics Laboratory The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA
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30
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Golemati S, Patelaki E, Nikita KS. Image-Based Motion and Strain Estimation of the Vessel Wall. ACTA ACUST UNITED AC 2019. [DOI: 10.1007/978-981-10-5092-3_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2023]
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31
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Weidenbacher L, Müller E, Guex AG, Zündel M, Schweizer P, Marina V, Adlhart C, Vejsadová L, Pauer R, Spiecker E, Maniura-Weber K, Ferguson SJ, Rossi RM, Rottmar M, Fortunato G. In Vitro Endothelialization of Surface-Integrated Nanofiber Networks for Stretchable Blood Interfaces. ACS APPLIED MATERIALS & INTERFACES 2019; 11:5740-5751. [PMID: 30668107 DOI: 10.1021/acsami.8b18121] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Despite major technological advances within the field of cardiovascular engineering, the risk of thromboembolic events on artificial surfaces in contact with blood remains a major challenge and limits the functionality of ventricular assist devices (VADs) during mid- or long-term therapy. Here, a biomimetic blood-material interface is created via a nanofiber-based approach that promotes the endothelialization capability of elastic silicone surfaces for next-generation VADs under elevated hemodynamic loads. A blend fiber membrane made of elastic polyurethane and low-thrombogenic poly(vinylidene fluoride- co-hexafluoropropylene) was partially embedded into the surface of silicone films. These blend membranes resist fundamental irreversible deformation of the internal structure and are stably attached to the surface, while also exhibiting enhanced antithrombotic properties when compared to bare silicone. The composite material supports the formation of a stable monolayer of endothelial cells within a pulsatile flow bioreactor, resembling the physiological in vivo situation in a VAD. The nanofiber surface modification concept thus presents a promising approach for the future design of advanced elastic composite materials that are particularly interesting for applications in contact with blood.
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Affiliation(s)
| | | | | | | | - Peter Schweizer
- Department of Materials Science and Engineering, Institute of Micro- and Nanostructure Research & Center for Nanoanalysis and Electron Microscopy , Friedrich-Alexander-Universität Erlangen-Nürnberg , 91058 Erlangen , Germany
| | | | - Christian Adlhart
- Institute of Chemistry and Biotechnology , Zurich University of Applied Sciences ZHAW , 8820 Wädenswil , Switzerland
| | - Lucie Vejsadová
- Institute of Chemistry and Biotechnology , Zurich University of Applied Sciences ZHAW , 8820 Wädenswil , Switzerland
| | - Robin Pauer
- Electron Microscopy Center , Empa, Swiss Federal Laboratories for Materials Science and Technology , 8600 Dübendorf , Switzerland
| | - Erdmann Spiecker
- Department of Materials Science and Engineering, Institute of Micro- and Nanostructure Research & Center for Nanoanalysis and Electron Microscopy , Friedrich-Alexander-Universität Erlangen-Nürnberg , 91058 Erlangen , Germany
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32
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Farzaneh S, Trabelsi O, Chavent B, Avril S. Identifying Local Arterial Stiffness to Assess the Risk of Rupture of Ascending Thoracic Aortic Aneurysms. Ann Biomed Eng 2019; 47:1038-1050. [DOI: 10.1007/s10439-019-02204-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 01/09/2019] [Indexed: 01/18/2023]
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33
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Iffrig E, Wilson JS, Zhong X, Oshinski JN. Demonstration of circumferential heterogeneity in displacement and strain in the abdominal aortic wall by spiral cine DENSE MRI. J Magn Reson Imaging 2018; 49:731-743. [PMID: 30295345 DOI: 10.1002/jmri.26304] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 07/30/2018] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Knowledge of tissue properties of the abdominal aorta can improve understanding of vascular disease and guide interventional approaches. Existing MRI methods to quantify aortic wall displacement and strain are unable to discern circumferential heterogeneity. PURPOSE To assess regional variation in abdominal aortic wall displacement and strain as a function of circumferential position using spiral cine displacement encoding with stimulated echoes (DENSE). STUDY TYPE Prospective. POPULATION Cardiovascular disease-free men (n = 8) and women (n = 9) ages 30-42. SEQUENCES Prospective electrocardiogram (ECG)-gated and navigator echo-gated spiral, cine 2D DENSE and retrospective ECG-gated phase contrast MR (PCMR) sequences at 3T. ASSESSMENT In-plane displacement values of the aortic wall acquired with DENSE were used to determine radial and circumferential aortic wall motion. A quadrilateral-based 2D strain calculation method was implemented to determine strain from the displacement field. Peak displacement and its radial and circumferential contributions as well as peak circumferential strain were compared among eight circumferential wall segments. Distensibility was calculated using PCMR and compared with homogenized circumferential strain. STATISTICAL TESTS To account for repeated measurements in volunteers, linear mixed models for mean sector values were created for displacement magnitude, circumferential displacement, radial displacement, and circumferential strain. Comparisons were made between sectors. Calculated distensibility and homogenized circumferential strain were compared using Bland-Altman analysis. Statistical significance was defined as P < 0.05. RESULTS Displacement was highest in the anterior wall (1.5 ± 0.7 mm) and was primarily in the radial as compared with circumferential direction (1.04 ± 0.05 mm vs. 0.81 ± 0.42 mm). Circumferential strain was highest in the lateral walls (left 0.16 ± 0.05 and right 0.21 ± 0.12) with homogenized circumferential strain of 0.14 ± 0.05. DATA CONCLUSION DENSE imaging in the abdominal aortic wall demonstrated that the anterior aortic wall exhibits the greatest displacement, while the lateral wall experiences the largest circumferential strain. LEVEL OF EVIDENCE 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:731-743.
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Affiliation(s)
- Elizabeth Iffrig
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA
| | - John S Wilson
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.,Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia
| | - Xiadong Zhong
- Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia
| | - John N Oshinski
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.,Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia
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34
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Farzaneh S, Trabelsi O, Avril S. Inverse identification of local stiffness across ascending thoracic aortic aneurysms. Biomech Model Mechanobiol 2018; 18:137-153. [DOI: 10.1007/s10237-018-1073-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 08/16/2018] [Indexed: 01/06/2023]
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35
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Emmott A, Alzahrani H, Alreshidan M, Therrien J, Leask RL, Lachapelle K. Transesophageal echocardiographic strain imaging predicts aortic biomechanics: Beyond diameter. J Thorac Cardiovasc Surg 2018; 156:503-512.e1. [DOI: 10.1016/j.jtcvs.2018.01.107] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 01/09/2018] [Accepted: 01/16/2018] [Indexed: 02/07/2023]
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36
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Wilson JS, Zhong X, Hair JB, Taylor WR, Oshinski J. In vivo quantification of regional circumferential Green strain in the thoracic and abdominal aorta by 2D spiral cine DENSE MRI. J Biomech Eng 2018; 141:2694731. [PMID: 30029261 DOI: 10.1115/1.4040910] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Indexed: 11/08/2022]
Abstract
INTRODUCTION Regional tissue mechanics play a fundamental role in patient-specific cardiovascular function. Nevertheless, regional assessments of aortic kinematics remain lacking due to the challenge of imaging the thin aortic wall. Herein, we present a novel application of DENSE (Displacement Encoding with Stimulated Echoes) MRI to quantify the circumferential Green strain of the thoracic and abdominal aorta. METHODS 2D spiral cine DENSE and steady-state free procession (SSFP) cine images were acquired at 3T at the infrarenal aorta (IAA), descending thoracic aorta (DTA), or distal aortic arch (DAA) in a pilot study of 6 healthy volunteers. DENSE data was processed with multiple custom noise-reduction techniques to calculate circumferential Green strain across 16 equispaced sectors around the aorta. Each volunteer was scanned twice to evaluate interstudy repeatability. RESULTS Circumferential strain was heterogeneously distributed in all volunteers and locations. Spatial heterogeneity index by location was 0.37 (IAA), 0.28 (DTA), and 0.59 (DAA). Mean peak strain by DENSE for each cross-section was consistent with the homogenized linearized strain estimated from SSFP cine. The mean difference in peak strain across all sectors following repeat imaging was -0.1±2.2%, with a mean absolute difference of 1.7%. CONCLUSIONS Aortic cine DENSE MRI is a viable non-invasive technique for quantifying heterogeneous regional aortic wall strain and has significant potential to improve patient-specific clinical assessments of numerous aortopathies, as well as to provide the lacking spatiotemporal data required to refine computational models of aortic growth and remodeling.
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Affiliation(s)
- John S Wilson
- Department of Radiology & Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Xiaodong Zhong
- Magnetic Resonance R&D Collaborations, Siemens Healthcare, Atlanta, GA, USA; Department of Radiology & Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Jackson B Hair
- Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA
| | - W Robert Taylor
- Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Division of Cardiology, Department of Medicine, Atlanta VA Medical Center, Decatur, GA, USA
| | - John Oshinski
- Department of Radiology & Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA; Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA
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37
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Loosli C, Moy L, Kress G, Mazza E, Ermanni P. Corrugated diaphragm shape design study for hemocompatible pulsatile ventricular assist devices. Comput Methods Biomech Biomed Engin 2018; 21:399-407. [PMID: 29996696 DOI: 10.1080/10255842.2018.1434623] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
We aim to maximize the pumping volume of a pulsatile ventricular assist device, where the diaphragm is covered with an endothelial cell layer. These cells are estimated to survive a cyclic strain up to fifteen percent. To increase the pumping volume under this strain constraint we use an approach based on corrugation of the diaphragm in its reference configuration. The paper explains the parametrization scheme for finding corrugation shapes, addresses modeling and evaluation schemes and reports on the results of a parameter study. The results show that corrugated diaphragm shapes are effective for increasing pumping volumes under a strain constraint.
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Affiliation(s)
- C Loosli
- a Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering , ETH Zürich , Tannenstr. 3 , CH-8092 Zürich , Switzerland
| | - L Moy
- a Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering , ETH Zürich , Tannenstr. 3 , CH-8092 Zürich , Switzerland
| | - G Kress
- a Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering , ETH Zürich , Tannenstr. 3 , CH-8092 Zürich , Switzerland
| | - E Mazza
- b Experimental Continuum Mechanics, Department of Mechanical and Process Engineering , ETH Zürich , Leonhardstr. 21 , CH-8092 Zürich , Switzerland
| | - P Ermanni
- a Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering , ETH Zürich , Tannenstr. 3 , CH-8092 Zürich , Switzerland
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38
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Bhave NM, Nienaber CA, Clough RE, Eagle KA. Multimodality Imaging of Thoracic Aortic Diseases in Adults. JACC Cardiovasc Imaging 2018; 11:902-919. [DOI: 10.1016/j.jcmg.2018.03.009] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Revised: 03/16/2018] [Accepted: 03/20/2018] [Indexed: 12/28/2022]
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39
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Satriano A, Guenther Z, White JA, Merchant N, Di Martino ES, Al-Qoofi F, Lydell CP, Fine NM. Three-dimensional thoracic aorta principal strain analysis from routine ECG-gated computerized tomography: feasibility in patients undergoing transcatheter aortic valve replacement. BMC Cardiovasc Disord 2018; 18:76. [PMID: 29720088 PMCID: PMC5932860 DOI: 10.1186/s12872-018-0818-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 04/24/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Functional impairment of the aorta is a recognized complication of aortic and aortic valve disease. Aortic strain measurement provides effective quantification of mechanical aortic function, and 3-dimenional (3D) approaches may be desirable for serial evaluation. Computerized tomographic angiography (CTA) is routinely performed for various clinical indications, and offers the unique potential to study 3D aortic deformation. We sought to investigate the feasibility of performing 3D aortic strain analysis in a candidate population of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS Twenty-one patients with severe aortic valve stenosis (AS) referred for TAVR underwent ECG-gated CTA and echocardiography. CTA images were analyzed using a 3D feature-tracking based technique to construct a dynamic aortic mesh model to perform peak principal strain amplitude (PPSA) analysis. Segmental strain values were correlated against clinical, hemodynamic and echocardiographic variables. Reproducibility analysis was performed. RESULTS The mean patient age was 81±6 years. Mean left ventricular ejection fraction was 52±14%, aortic valve area (AVA) 0.6±0.3 cm2 and mean AS pressure gradient (MG) 44±11 mmHg. CTA-based 3D PPSA analysis was feasible in all subjects. Mean PPSA values for the global thoracic aorta, ascending aorta, aortic arch and descending aorta segments were 6.5±3.0, 10.2±6.0, 6.1±2.9 and 3.3±1.7%, respectively. 3D PSSA values demonstrated significantly more impairment with measures of worsening AS severity, including AVA and MG for the global thoracic aorta and ascending segment (p<0.001 for all). 3D PSSA was independently associated with AVA by multivariable modelling. Coefficients of variation for intra- and inter-observer variability were 5.8 and 7.2%, respectively. CONCLUSIONS Three-dimensional aortic PPSA analysis is clinically feasible from routine ECG-gated CTA. Appropriate reductions in PSSA were identified with increasing AS hemodynamic severity. Expanded study of 3D aortic PSSA for patients with various forms of aortic disease is warranted.
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Affiliation(s)
- Alessandro Satriano
- Stephenson Cardiac Imaging Centre, University of Calgary, Calgary, Alberta, Canada.,Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, South Health Campus, 4448 Front Street SE, Calgary, Alberta, T3M 1M4, Canada
| | - Zachary Guenther
- Stephenson Cardiac Imaging Centre, University of Calgary, Calgary, Alberta, Canada.,Department of Diagnostic Imaging, Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - James A White
- Stephenson Cardiac Imaging Centre, University of Calgary, Calgary, Alberta, Canada.,Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, South Health Campus, 4448 Front Street SE, Calgary, Alberta, T3M 1M4, Canada
| | - Naeem Merchant
- Stephenson Cardiac Imaging Centre, University of Calgary, Calgary, Alberta, Canada.,Department of Diagnostic Imaging, Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Elena S Di Martino
- Department of Civil Engineering and Centre for Bioengineering Research and Education, University of Calgary, Calgary, Alberta, Canada
| | - Faisal Al-Qoofi
- Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, South Health Campus, 4448 Front Street SE, Calgary, Alberta, T3M 1M4, Canada
| | - Carmen P Lydell
- Stephenson Cardiac Imaging Centre, University of Calgary, Calgary, Alberta, Canada.,Department of Diagnostic Imaging, Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Nowell M Fine
- Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, South Health Campus, 4448 Front Street SE, Calgary, Alberta, T3M 1M4, Canada.
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40
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Pasta S, Agnese V, Di Giuseppe M, Gentile G, Raffa GM, Bellavia D, Pilato M. In Vivo Strain Analysis of Dilated Ascending Thoracic Aorta by ECG-Gated CT Angiographic Imaging. Ann Biomed Eng 2017; 45:2911-2920. [DOI: 10.1007/s10439-017-1915-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 08/31/2017] [Indexed: 01/13/2023]
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41
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Bachmann BJ, Bernardi L, Loosli C, Marschewski J, Perrini M, Ehrbar M, Ermanni P, Poulikakos D, Ferrari A, Mazza E. A Novel Bioreactor System for the Assessment of Endothelialization on Deformable Surfaces. Sci Rep 2016; 6:38861. [PMID: 27941901 PMCID: PMC5150819 DOI: 10.1038/srep38861] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 11/15/2016] [Indexed: 12/28/2022] Open
Abstract
The generation of a living protective layer at the luminal surface of cardiovascular devices, composed of an autologous functional endothelium, represents the ideal solution to life-threatening, implant-related complications in cardiovascular patients. The initial evaluation of engineering strategies fostering endothelial cell adhesion and proliferation as well as the long-term tissue homeostasis requires in vitro testing in environmental model systems able to recapitulate the hemodynamic conditions experienced at the blood-to-device interface of implants as well as the substrate deformation. Here, we introduce the design and validation of a novel bioreactor system which enables the long-term conditioning of human endothelial cells interacting with artificial materials under dynamic combinations of flow-generated wall shear stress and wall deformation. The wall shear stress and wall deformation values obtained encompass both the physiological and supraphysiological range. They are determined through separate actuation systems which are controlled based on validated computational models. In addition, we demonstrate the good optical conductivity of the system permitting online monitoring of cell activities through live-cell imaging as well as standard biochemical post-processing. Altogether, the bioreactor system defines an unprecedented testing hub for potential strategies toward the endothelialization or re-endothelialization of target substrates.
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Affiliation(s)
- Björn J. Bachmann
- ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies, Sonneggstrasse 3, 8092 Zurich, Switzerland
| | - Laura Bernardi
- ETH Zurich, Institute for Mechanical Systems, Leonhardstrasse 21, 8092 Zurich, Switzerland
| | - Christian Loosli
- ETH Zurich, Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering, Tannenstrasse 3, CH-8092 Zurich, Switzerland
| | - Julian Marschewski
- ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies, Sonneggstrasse 3, 8092 Zurich, Switzerland
| | - Michela Perrini
- ETH Zurich, Institute for Mechanical Systems, Leonhardstrasse 21, 8092 Zurich, Switzerland
- University Hospital Zurich, Department of Obstetrics, Zurich, Switzerland
| | - Martin Ehrbar
- University Hospital Zurich, Department of Obstetrics, Zurich, Switzerland
| | - Paolo Ermanni
- ETH Zurich, Laboratory of Composite Materials and Adaptive Structures, Department of Mechanical and Process Engineering, Tannenstrasse 3, CH-8092 Zurich, Switzerland
| | - Dimos Poulikakos
- ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies, Sonneggstrasse 3, 8092 Zurich, Switzerland
| | - Aldo Ferrari
- ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies, Sonneggstrasse 3, 8092 Zurich, Switzerland
| | - Edoardo Mazza
- ETH Zurich, Institute for Mechanical Systems, Leonhardstrasse 21, 8092 Zurich, Switzerland
- Empa, Swiss Federal Laboratories for Materials Science & Technology, Überlandstr. 129, 8600 Dübendorf, Switzerland
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