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

Applicant Tsamis Alkiviadis
Number 139684
Funding scheme Fellowships for advanced researchers
Research institution
Institution of higher education Institution abroad - IACH
Main discipline Mechanical Engineering
Start/End 01.02.2012 - 31.01.2013
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All Disciplines (4)

Discipline
Mechanical Engineering
Cardiovascular Research
Clinical Cardiovascular Research
Cardiovascular Diseases

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 (English)

Lead
Aortic disease is a significant cause of death in developed countries. Microstructural alterations of connective fibers in the aorta can lead to functional changes associated with aortic disease. The regional variation of aortic wall fiber architecture in aging and disease, and the associated biomechanical behavior of the aorta, are still not fully understood. This work will attempt to shed light on the interrelation among these processes.
Lay summary

Research objectives and content

I have designed the following specific aims: (i) assess elastin and collagen content and 3D distributions in specified locations of the human aorta in different ages, (ii) describe fiber architecture in aortic aneurysm or dissection, (iii) assess associations of Marfan syndrome and bicuspid aortic valve with regional changes in aortic wall fiber architecture, and (iv) incorporate fiber content and architecture data using newly developed techniques to simulate aging, aneurysm formation and dissection in the human aorta.

The results of my research suggest that the reduced undulation of collagen and elastin fibers in the medial-intimal half of ascending thoracic aortic aneurysm wall could predispose the formation of an intimal tissue tear, or the initiation of a dissection. Also, computational simulation results show that the number density and failure energy of the radially-running collagen fibers control the delamination strength of the aorta.

Scientific and societal context of the research project

This work will enhance our understanding on the pathophysiology of aortic disease and can lead to a subject-specific simulation tool, which would enable the precise prediction of aortic remodeling in aging and disease and could possibly guide the decision-making in associated clinical diagnosis and treatment.

Direct link to Lay Summary Last update: 04.12.2012

Responsible applicant and co-applicants

Publications

Publication
Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review.
Tsamis Alkiviadis, Krawiec Jeffrey T, Vorp David A (2013), Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review., in Journal of the Royal Society, Interface, 10(83), 20121004-20121004.
Association of Wall Stress of Human Intracranial Saccular Aneurysm With Coil Packing Density After Coil Embolization
Pichamuthu Joseph E., Tsamis Alkiviadis, Jankowitz Brian T., Vorp David A. (2012), Association of Wall Stress of Human Intracranial Saccular Aneurysm With Coil Packing Density After Coil Embolization, in ASME 2012 Summer Bioengineering Conference, Fajardo, Puerto Rico, USAThe American Society of Mechanical Engineers, New York, NY, USA.

Collaboration

Group / person Country
Types of collaboration
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. 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. 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
2013 Life Sciences Switzerland (LS2) Annual Meeting Poster Fiber architecture in the longitudinal-radial and circumferential-radial planes of human ascending thoracic aortic media 31.01.2013 University of Zürich, Campus Irchel, Zürich, Switzerland Tsamis Alkiviadis;
2012 Annual Meeting of the Biomedical Engineering Society (BMES) Talk given at a conference Fiber architecture in the longitudinal-radial and circumferential-radial planes of human ascending thoracic aortic media 24.10.2012 Georgia World Congress Center, Atlanta, Georgia, United States of America Tsamis Alkiviadis;
2012 Annual Meeting of the Biomedical Engineering Society Poster A custom image analysis algorithm for characterization of aortic wall connective fiber architecture from multiphoton microscopy imaging 24.10.2012 Georgia World Congress Center, Atlanta, Georgia, United States of America Tsamis Alkiviadis;
2012 Annual Meeting of the Biomedical Engineering Society (BMES) Talk given at a conference Effect of geometry on wall stresses in a computational model of the Heineke-Mikulicz strictureplasty 24.10.2012 Georgia World Congress Center, Atlanta, Georgia, United States of America Tsamis Alkiviadis;
Translation Science 2012 Poster Custom image-analysis tool for quantifying aortic wall architecture from multiphoton microscopy 03.10.2012 University of Pittsburgh, Alumni Hall, Pittsburgh, Pennsylvania, United States of America Tsamis Alkiviadis;
Translation Science 2012 Poster Development of a "phantom" multiphoton microscopy image of the aortic wall using input microstructural parameters of the connective fiber architecture 03.10.2012 University of Pittsburgh, Alumni Hall, Pittsburgh, Pennsylvania, United States of America Tsamis Alkiviadis;
Wound Healing Research Seminar Series Individual talk Multi-photon interrogation and quantification of fiber architecture in soft, fibrous tissue 13.09.2012 Eye and Ear Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Tsamis Alkiviadis;
13th Biennial Meeting of the International Society for Applied Cardiovascular Biology (ISACB) Poster Collagen fiber architecture in the longitudinal-radial and circumferential-radial planes of ascending aorta is distinctly different among bicuspid aortic valve and tricuspid aortic valve patients with ascending aortic aneurysm 12.09.2012 University College London, Institute of Child Health, London, Great Britain and Northern Ireland Tsamis Alkiviadis;
ASME Summer Bioengineering Conference Talk given at a conference Association of wall stress of human intracranial saccular aneurysm with coil packing density after coil embolization 20.06.2012 El Conquistador Resort, Fajardo, Puerto Rico Tsamis Alkiviadis;
7th Annual Postdoctoral Data & Dine Symposium Poster Effect of geometry on stress distribution in a computational model of the Heineke-Mikulicz strictureplasty 01.05.2012 University of Pittsburgh, William Pitt Union Assembly Room and Ballroom, Pittsburgh, Pennsylvania, United States of America Tsamis Alkiviadis;
McGowan Institute for Regenerative Medicine Annual Scientific Retreat Poster Finite element analysis of a tissue engineered vascular graft 04.03.2012 Nemacolin Woodlands Resort, Farmington, Pennsylvania, United States of America Tsamis Alkiviadis;
McGowan Institute for Regenerative Medicine Annual Scientific Retreat Poster [BEST POSTER AWARD]: Effect of geometry on stress distribution in a computational model of the Heineke-Mikulicz strictureplasty 04.03.2012 Nemacolin Woodlands Resort, Farmington, Pennsylvania, United States of America Tsamis Alkiviadis;


Awards

Title Year
Award for Best Poster. Category: Computational Modeling. McGowan Institute for Regenerative Medicine Scientific Retreat, Nemacolin Woodlands Resort, Farmington, PA, USA. 2012

Associated projects

Number Title Start Funding scheme
145399 CHARACTERIZATION AND MODELING OF FIBER ARCHITECTURE OF HUMAN AORTA IN HEALTH AND DISEASE 01.02.2013 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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