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