Atherosclerosis is a progressive systemic disease of the wall of large arteries. It is characterized by lipids deposits and accumulation of fibrous elements in the arterial vessel wall, called plaques. Its clinical history can be very diverse, with some individuals experiencing slowly progressive symptoms, while others are asymptomatic for decades and then experience acute dramatic clinical events. Several studies have indicated that plaque pathophysiology is determined not primarily by size and the level of luminal narrowing, but by its composition and inflammatory state. The deeper understanding of the role of inflammation in the pathogenesis of atherosclerosis identifies new important markers for the detection and risk stratification of otherwise asymptomatic atherosclerotic lesions and it opens new possibilities for therapeutic intervention. In this scenario, it becomes relevant to develop non-invasive techniques to quantify plaque inflammation. Dynamic contrast enhanced (DCE) MRI is an imaging technique extensively used to study the vascularity of tumors. It takes advantage of the administration of clinically-available MRI contrast agents (i.e., Gadolinium (Gd)-chelates), to quantify the extent of tissues' neovasculature and its physiological characteristics. Promising preliminary studies have shown that DCE-MRI can characterize plaque neovascularization, a marker of inflammation, in patients with carotid atherosclerosis. In this dissertation we further investigate the potential of DCE-MRI to be a surrogate imaging marker of plaque inflammation. We explore the correlation between plaque neovascularization and DCE-MRI, the technique’s reproducibility, as well as its performance as a read-out for novel anti-inflammatory therapies in atherosclerotic rabbits. Following, we compare DCE-MRI with other imaging techniques targeting plaque inflammation and we test its use in clinical studies in patients with carotid atherosclerosis.
|Advisor:||Fayad, Zahi A.|
|Commitee:||Axel, Leon, Greengard, Leslie, Kaplan, Ehud, Peskin, Charles, Sanchez, Roberto|
|School:||Mount Sinai School of Medicine of New York University|
|Department:||Biophysics, Structural Biology, and Biomathematics|
|School Location:||United States -- New York|
|Source:||DAI-B 71/05, Dissertation Abstracts International|
|Subjects:||Biomedical engineering, Medical imaging, Computer science|
|Keywords:||Atherosclerosis, Dynamic contrast enhanced, Inflammation, MRI, Neovascularization|
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