Fellowship for Haggerty: NIH F32 Postdoctoral Fellowship

  • Fornwalt, Brandon (PI)
  • Haggerty, Christopher (CoI)

Grants and Contracts Details


Abdominal aortic aneurysm (AAA) rupture is the 13th leading cause of death in the US. While prophylactic surgical repair is an effective treatment, there are significant mortality risks associated with the procedure. Since most aneurysms do not rupture, these surgical risks may outweigh the benefits of repair in many cases. However, there are currently no means to accurately identify an aneurysm that will rupture to effectively evaluate the relative risk of rupture versus repair. The big-picture goal of this research program is to improve clinical care for patients with AAA by establishing sensitive, non-invasive markers for aneurysm rupture that can be used to better identify patients who should undergo surgical repair. Aneurysm size, as determined by medical imaging, is currently the most common method used to evaluate AAA rupture risk. However, recent advances in magnetic resonance imaging (MRI) allow for more sophisticated, high resolution assessments of the aorta. For example, quantifying the dynamic changes in aortic size and shape with systolic pressure pulses can be used to assess the mechanical properties of the aortic wall, such as its distensibility or stiffness. Since AAA rupture occurs when aneurysm stress exceeds mechanical strength, we hypothesize that non-invasive quantification of these mechanical and structural properties will lead to better rupture predictions. The first step in evaluating our hypothesis is to demonstrate proof of concept for this imaging-based paradigm in an animal disease model. The most widely used model of AAA is the ApoE-/-/angiotensin-II mouse model, which was developed and has been extensively studied our institution over the past 15 years. This expertise, coupled with our cardiovascular imaging abilities in both mice and humans, uniquely qualifies us to successfully carry out this research. To develop mechanical rupture markers, we propose a two-pronged approach. We first seek to relate the macroscopic mechanics measured via MRI to the microscopic function of cells and enzymes, such a matrix metalloproteinases (MMPs), which are important deterministic factors in aneurysm grown and remodeling. Serial assessment of these mechanical measures in mouse AAA will then be related to rupture outcomes to evaluate their predictive value. The long-term objective of this proposal is to take these sensitive imaging markers and translate them to human studies to improve clinical decision-making.
Effective start/end date9/1/144/15/15


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