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CHARACTERIZATION AND MODELING OF FIBER ARCHITECTURE OF HUMAN AORTA IN HEALTH AND DISEASE

Applicant Tsamis Alkiviadis
Number 145399
Funding scheme Fellowships for advanced researchers
Research institution Department of Bioengineering Swanson School of Engineering University of Pittsburgh
Institution of higher education Institution abroad - IACH
Main discipline Mechanical Engineering
Start/End 01.02.2013 - 31.01.2014
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All Disciplines (6)

Discipline
Mechanical Engineering
Cardiovascular Research
Clinical Cardiovascular Research
Cardiovascular Diseases
Congenital Disorders
Biomedical Engineering

Keywords (13)

Human aorta; Aging; Aneurysm; Dissection; Marfan syndrome; Bicuspid aortic valve; Elastin; Collagen; Microstructure; Architecture; Multiphoton microscopy; Custom image-based analysis; Computational modeling

Lay Summary (French)

Lead
Maladie aortique est une cause importante de décès dans les pays développés. Modifications microstructurales dans l'aorte peut entraîner des changements fonctionnels associés à la maladie aortique. La variation régionale de l'architecture de fibre à la paroi aortique dans le vieillissement et la maladie, et le comportement biomécanique associée de l'aorte, ne sont pas encore entièrement compris. Ce travail va tenter de faire la lumière sur l'interrelation entre ces processus.
Lay summary

Contenu et objectifs du travail de recherche

J'ai conçu les objectifs spécifiques suivants: (i) évaluer la teneur en élastine et de collagène et leurs distributions en 3D dans des endroits précis de l'aorte humaine à des âges différentes, (ii) décrire l'architecture des fibres dans l'anévrisme ou la dissection aortique, (iii) évaluer les associations du syndrome de Marfan et de la valve aortique bicuspide avec les modifications de l'architecture de fibre régionale dans la paroi aortique, et (iv) incorporer la teneur en fibres et les données d'architecture à l'aide de nouvelles techniques afin de simuler le vieillissement et le formation d'un anévrisme ou une dissection à l'aorte humaine.

Les résultats de mes recherches suggèrent que l'ondulation réduite des fibres de collagène et d'élastine dans la moitié médiale-intimale de la paroi anévrisme thoracique ascendante de l'aorte pourrait prédisposer à la formation d'une déchirure intimale ou le déclenchement d'une dissection. En outre, les résultats des simulations informatiques montrent que la densité de nombre et l'énergie de rupture des fibres de collagène radiale contrôlent la résistance à la délamination de l'aorte.

Contexte scientifique et social du projet de recherche

Ce travail permettra d'améliorer notre compréhension de la physiopathologie de la maladie aortique et peut conduire à un outil de simulation des sujets spécifiques, ce qui permettrait à la prédiction précise de remodelage aortique dans le vieillissement et la maladie et pourrait orienter la prise de décision dans le diagnostic clinique et le traitement associé.

Direct link to Lay Summary Last update: 18.12.2012

Responsible applicant and co-applicants

Publications

Publication
Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion
Stearns-Reider K.M., D'Amore A., Beezhold K., Rothrauff B., Cavalli L., Wagner W.R., Vorp D.A., Tsamis A., Shinde S., Zhang C., Barchowsky A., Rando T.A., Tuan R.S., Ambrosio F. (2017), Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion, in Aging Cell, 16(3), 518-528.
Constitutive modeling of ascending thoracic aortic aneurysms using microstructural parameters.
Pasta Salvatore, Phillippi Julie A, Tsamis Alkiviadis, D'Amore Antonio, Raffa Giuseppe M, Pilato Michele, Scardulla Cesare, Watkins Simon C, Wagner William R, Gleason Thomas G, Vorp David A (2016), Constitutive modeling of ascending thoracic aortic aneurysms using microstructural parameters., in Medical engineering & physics, 38(2), 121-30.
Extracellular matrix fiber microarchitecture is region-specific in bicuspid aortic valve-associated ascending aortopathy.
Tsamis Alkiviadis, Phillippi Julie A, Koch Ryan G, Chan Patrick G, Krawiec Jeffrey T, D'Amore Antonio, Watkins Simon C, Wagner William R, Vorp David A, Gleason Thomas G (2016), Extracellular matrix fiber microarchitecture is region-specific in bicuspid aortic valve-associated ascending aortopathy., in The Journal of thoracic and cardiovascular surgery, 151(6), 1718-1728.
Correlations between transmural mechanical and morphological properties in porcine thoracic descending aorta.
Hemmasizadeh Ali, Tsamis Alkiviadis, Cheheltani Rabee, Assari Soroush, D'Amore Antonio, Autieri Michael, Kiani Mohammad F, Pleshko Nancy, Wagner William R, Watkins Simon C, Vorp David, Darvish Kurosh (2015), Correlations between transmural mechanical and morphological properties in porcine thoracic descending aorta., in Journal of the mechanical behavior of biomedical materials, 47, 12-20.
A custom image-based analysis tool for quantifying elastin and collagen micro-architecture in the wall of the human aorta from multi-photon microscopy.
Koch Ryan G, Tsamis Alkiviadis, D'Amore Antonio, Wagner William R, Watkins Simon C, Gleason Thomas G, Vorp David A (2014), A custom image-based analysis tool for quantifying elastin and collagen micro-architecture in the wall of the human aorta from multi-photon microscopy., in Journal of biomechanics, 47(5), 935-943.
A mechanistic model on the role of "radially-running" collagen fibers on dissection properties of human ascending thoracic aorta.
Pal Siladitya, Tsamis Alkiviadis, Pasta Salvatore, D'Amore Antonio, Gleason Thomas G, Vorp David A, Maiti Spandan (2014), A mechanistic model on the role of "radially-running" collagen fibers on dissection properties of human ascending thoracic aorta., in Journal of biomechanics, 47(5), 981-988.
Effect of aneurysm on biomechanical properties of "radially-oriented" collagen fibers in human ascending thoracic aortic media.
Tsamis Alkiviadis, Pal Siladitya, Phillippi Julie A, Gleason Thomas G, Maiti Spandan, Vorp David A (2014), Effect of aneurysm on biomechanical properties of "radially-oriented" collagen fibers in human ascending thoracic aortic media., in Journal of biomechanics, 47(16), 3820-4.
Elasticity and geometry: a computational model of the Heineke-Mikulicz strictureplasty.
Tsamis Alkiviadis, Pocivavsek Luka, Vorp David A (2014), Elasticity and geometry: a computational model of the Heineke-Mikulicz strictureplasty., in Biomechanics and modeling in mechanobiology, 13(6), 1185-98.
A Custom Image-Based Analysis Tool for Quantifying Elastin and Collagen Fiber Micro-Architecture in the Wall of the Human Aorta From Multi-Photon Microscopy Images
Koch Ryan G., Tsamis Alkiviadis, D’Amore Antonio, Wagner William R., Vorp David A. (2013), A Custom Image-Based Analysis Tool for Quantifying Elastin and Collagen Fiber Micro-Architecture in the Wall of the Human Aorta From Multi-Photon Microscopy Images, in ASME 2013 Summer Bioengineering Conference, Sunriver, Oregon, USA.
Fiber micro-architecture in the longitudinal-radial and circumferential-radial planes of ascending thoracic aortic aneurysm media.
Tsamis Alkiviadis, Phillippi Julie A, Koch Ryan G, Pasta Salvatore, D'Amore Antonio, Watkins Simon C, Wagner William R, Gleason Thomas G, Vorp David A (2013), Fiber micro-architecture in the longitudinal-radial and circumferential-radial planes of ascending thoracic aortic aneurysm media., in Journal of biomechanics, 46(16), 2787-2794.
Region-Specific Medial Fiber Micro-Architecture in the Longitudinal-Radial and Circumferential-Radial Planes of Ascending Thoracic Aortic Aneurysm Among Bicuspid and Tricuspid Aortic Valve Patients
Tsamis Alkiviadis, Phillippi Julie A., Koch Ryan G., Krawiec Jeffrey T., D’Amore Antonio, Watkins Simon C., Wagner William R., Vorp David A., Gleason Thomas G. (2013), Region-Specific Medial Fiber Micro-Architecture in the Longitudinal-Radial and Circumferential-Radial Planes of Ascending Thoracic Aortic Aneurysm Among Bicuspid and Tricuspid Aortic Valve Patients, in ASME 2013 Summer Bioengineering Conference, Sunriver, Oregon, USA.

Collaboration

Group / person Country
Types of collaboration
Prof. William R. Wagner, Cardiovascular Engineering Lab, McGowan Institute for Regenerative Medicine United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. David A. Vorp, Vascular Bioengineering Laboratory, University of Pittsburgh United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Simon C. Watkins, Center for Biologic Imaging, University of Pittsburgh United States of America (North America)
- Publication
- Research Infrastructure
Prof. Adam W. Feinberg, Regenerative Biomaterials & Therapeutics Group, Carnegie Mellon University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Thomas G. Gleason, Thoracic Aortic Disease Research Laboratory, University of Pittsburgh United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
XXXII LIAC Meeting on Vascular Research Individual talk Multiscale mechanics and engineering of soft biological tissues 14.09.2016 City Library, Ustica, Italy Tsamis Alkiviadis;
10th World Biomaterials Congress Talk given at a conference [Polymer Solutions Trainee Award]: Fibronectin-based nanomechanical biosensors towards measuring cell-generated strains during tissue morphogenesis 17.05.2016 Montreal Convention Center, Montreal, Quebec, Canada Tsamis Alkiviadis;
Invited job talk Individual talk Mechanics, modelling and engineering of soft biological tissues at multiple time and length scales 27.04.2016 Faculty of Science, Arts Building, University of East Anglia, Norwich, Norfolk, Great Britain and Northern Ireland Tsamis Alkiviadis;
Invited job talk Individual talk Multiscale mechanics, modelling and engineering of soft biological tissues 20.04.2016 College of Engineering, Mathematics and Physical Sciences, Harrison Building, University of Exeter, Great Britain and Northern Ireland Tsamis Alkiviadis;
McGowan Institute for Regenerative Medicine Annual Scientific Retreat Poster ECM-based nanomechanical biosensors for measuring cell-generated 3D mechanical strains during tissue morphogenesis 06.03.2016 Nemacolin Woodlands Resort, Farmington, Pennsylvania, United States of America Tsamis Alkiviadis;
2015 Annual Meeting of the Biomedical Engineering Society Poster Tracking cell-generated compaction strains in 3D tissue using fibronectin-based nanomechanical biosensors 07.10.2015 Tampa Convention Center, Tampa, Florida, United States of America Tsamis Alkiviadis;
2015 Summer Biomechanics, Bioengineering and Biotransport Conference Talk given at a conference Role of aneurysm on failure properties of "radially-oriented" collagen fibers in human ascending thoracic aortic media 17.06.2015 Snowbird Resort and Conference Center, Snowbird, Utah, United States of America Tsamis Alkiviadis;
2014 Annual Meeting of the Biomedical Engineering Society Talk given at a conference Role of aneurysm on biomechanics of radially-oriented fibers in human ascending thoracic aorta 22.10.2014 Henry B. Gonzalez Convention Center, San Antonio, Texas, United States of America Tsamis Alkiviadis;
7th World Congress of Biomechanics Poster A mechanistic model of dissection of human ascending thoracic aorta 06.07.2014 John B. Hynes Veterans Memorial Convention Center, Boston, Massachusetts, United States of America Tsamis Alkiviadis;
7th World Congress of Biomechanics Talk given at a conference Biomechanical and micro-architectural investigation of ascending thoracic aortic aneurysms with different aortic valve phenotypes 06.07.2014 John B. Hynes Veterans Memorial Convention Center, Boston, Massachusetts, United States of America Tsamis Alkiviadis;
Third Annual Symposium on Regenerative Rehabilitation Poster The effect of age on structural and mechanical properties of skeletal muscle extracellular matrix 10.04.2014 Mission Bay Conference Center at University of California, San Francisco, San Francisco, California, United States of America Tsamis Alkiviadis;
14th Biennial Meeting of the International Society for Applied Cardiovascular Biology Poster Aortic valve morphology correlates with circumferentially-distinct arrangement of radially-oriented fibers in aneurysm of ascending thoracic aorta 02.04.2014 Tudor Arms Doubletree Hotel, Cleveland, Ohio, United States of America Tsamis Alkiviadis;
McGowan Institute for Regenerative Medicine Annual Scientific Retreat Poster Aortic valve morphology correlates with circumferentially-distinct arrangement of radially-oriented fibers in aneurysm of ascending thoracic aorta 09.03.2014 Nemacolin Woodlands Resort, Farmington, Pennsylvania, United States of America Tsamis Alkiviadis;
McGowan Institute for Regenerative Medicine Annual Scientific Retreat Individual talk Aortic valve morphology predicts spatially-distinct fiber architecture in ascending aortic aneurysm 09.03.2014 Nemacolin Woodlands Resort, Farmington, Pennsylvania, United States of America Tsamis Alkiviadis;
Invited job talk Individual talk Quantification of fiber architecture in soft, fibrous tissue using multi-photon microscopy image analysis 05.02.2014 School of Dental Medicine, Center for Craniofacial Regeneration, University of Pittsburgh, United States of America Tsamis Alkiviadis;
Invited laboratory seminar Individual talk Multi-photon analysis of the role of fiber micro-architecture on aneurysm and dissection characteristics of human ascending thoracic aorta 16.01.2014 Laboratory for Bio-Inspired Interfaces, Department of Materials Science and Engineering, MIT, United States of America Tsamis Alkiviadis;
Science Convergence 2013 Poster Three-dimensional reconstruction of aortic elastin and collagen fibers from multi-photon micrographs 02.10.2013 University of Pittsburgh, Alumni Hall, Pittsburgh, Pennsylvania, United States of America Tsamis Alkiviadis;
2013 Annual Meeting of the Biomedical Engineering Society Talk given at a conference Aortic valve morphology predicts spatially-distinct fiber architecture in ascending aortic aneurysm 25.09.2013 Washington State Convention Center, Seattle, Washington, United States of America Tsamis Alkiviadis;
2013 Annual Meeting of the Biomedical Engineering Society Talk given at a conference Mechanistic model on role of "radially-running" collagen in dissection properties of ascending aorta 25.09.2013 Washington State Convention Center, Seattle, Washington, United States of America Tsamis Alkiviadis;
19th Congress of the European Society of Biomechanics Talk given at a conference Aortic valve morphology dictates region-specific fiber architecture in human ascending thoracic aortic aneurysms 25.08.2013 Conference and Cultural Centre of the University of Patras, Patras, Greece Tsamis Alkiviadis;
ASME Summer Bioengineering Conference Talk given at a conference Region-specific medial fiber micro-architecture in the longitudinal-radial and circumferential-radial planes of ascending thoracic aortic aneurysm among bicuspid and tricuspid aortic valve patients 26.06.2013 Sunriver Resort, Sunriver, Oregon, United States of America Tsamis Alkiviadis;
ASME Summer Bioengineering Conference Poster [Best poster award]: A custom image-based analysis tool for quantifying elastin and collagen fiber micro-architecture in the wall of the human aorta from multi-photon microscopy images 26.06.2013 Sunriver Resort, Sunriver, Oregon, United States of America Tsamis Alkiviadis;
McGowan Institute for Regenerative Medicine Annual Scientific Retreat Poster Aortic valve morphology dictates region-specific fiber architecture in human ascending thoracic aortic aneurysms 07.03.2013 Nemacolin Woodlands Resort, Farmington, Pennsylvania, United States of America Tsamis Alkiviadis;


Awards

Title Year
Polymer Solutions Trainee Award. 10th World Biomaterials Congress, Montreal Convention Center, Montreal, Quebec, Canada. 2016
Award for Best Poster in the ASME Bioengineering Division Bachelor’s student paper competition for Bioengineering undergraduate student Mr. Ryan G. Koch, for whom I acted as primary mentor during my postdoc at the University of Pittsburgh. Award Category: Fluid Mechanics, Biotransport, Cellular and Tissue Engineering. 2013 Summer Bioengineering Conference, Sunriver Resort, Sunriver, Oregon, USA. 2013

Associated projects

Number Title Start Funding scheme
139684 CHARACTERIZATION AND MODELING OF FIBER ARCHITECTURE OF HUMAN AORTA IN HEALTH AND DISEASE 01.02.2012 Fellowships for advanced researchers

Abstract

Aortic disease is a significant cause of death in developed countries. The most common forms of aortic disease are aneurysm, dissection, atherosclerotic occlusion and a general stiffening of the normally-elastic aorta that is thought to be a natural consequence of aging. There are many co-morbid conditions that can lead to one or more of these diseases, including hypertension, genetic mutations (such as Marfan syndrome), and developmental defects (such as bicuspid aortic valve). The aorta is elastic and this design aids in the propulsion of blood downstream to the systemic vasculature. Connective fibers within the aortic wall impart these elastic properties, and it is often alteration of the quantity and/or architecture of these fibers that lead to mechanical and hence functional changes associated with aortic disease. The aorta also has distinct regions or segments that are more susceptible to certain types of disease than others. At present, the regional variation in aortic wall fiber content and architecture in aging and disease - including co-morbid conditions such as Marfan syndrome and bicuspid aortic valve - and the associated biomechanical behavior of the aorta over the lifespan are still not fully understood. This work will attempt to shed light on the interrelation among the aforementioned processes. That is, I will: (1) Assess the regional variation in elastin and collagen content and fiber distributions in 6 specified segments of the human aorta obtained from subjects within a wide age range; (2) Correlate the nature of the fiber architecture and content with the formation of ascending and descending thoracic aortic aneurysm or dissection; (3) Seek associations of Marfan syndrome and bicuspid aortic valve with regional alterations in the fiber architecture and mechanical properties of the aortic wall; and (4) Synthesize these observations into a consistent computational model to simulate aging, aneurysm formation and dissection in the human aorta. An expected long-term outcome of such work would be a subject-specific simulation tool that would enable the precise prediction of aortic remodeling in health and disease, and could possibly guide the decision-making in clinical diagnosis and treatment.
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