Aortic wall stiffness is a fundamental biomechanical parameter that reflects the structural integrity of normal and aneurysmal aortic tissue. Abdominal aortic aneurysms (AAA) enlarge over time and lead to sudden rupture and death in up to 90% of patients. Surgical or endovascular aneurysm repair (EVAR) is recommended for AAAs > 5.5 cm in diameter. However, smaller AAAs (< 5 cm) progress to rupture, and larger AAAs (> 5 cm) remain stable. It is shown that rate of AAA expansion is a better indicator of AAA rupture than AAA diameter. However, rate of AAA expansion is not able to identify patients who present initially with impending AAA rupture and therefore depend on AAA diameter for initial assessment. Despite the poor prognostic value of aortic diameter, it is still the primary parameter used to time surgical repair. It is known that changes in stiffness of AAA can reveal important information on extra-cellular matrix content; a key factor in the pathophysiological development of AAA and the risk for rupture. Therefore, a non-invasive, spatially resolved estimate of aortic stiffness may provide a superior determinant of the risk for rupture compared to the currently used anatomical measures. The relationship between non-invasively measured wall stiffness (WS) and the structural integrity of the aortic wall must be further elucidated. To date, aortic stiffness has been measured with invasive catheter or non-invasive ultrasound-based methods, such as pulse-wave velocity (PWV) or pulse-wave imaging (PWI), or magnetic resonance imaging (MRI) based PWV to provide only an indirect global estimate of aortic WS. Furthermore, these methods can neither spatially resolve WS (important in understanding AAA formation), nor temporally resolve the aortic WS across the cardiac cycle; this is critical since the loading conditions (i.e., pressure) changes across the cardiac cycle and influences stiffness estimates. Because of these limitations, indirect measurements of global aortic stiffness via catheter, ultrasound, or MRI have not been widely adopted. The PI's lab has developed a novel, non-invasive, 3D spatially and temporally resolved measure of aortic stiffness termed Aortic Magnetic Resonance Elastography (AMRE). We hypothesize that this innovative AMRE-derived stiffness will improve our understanding of AAA pathogenesis and provide superior prognostic information compared to aortic diameter. Therefore, the overall goal of this proposal is to validate in-vivo AMRE against both ex-vivo mechanical testing and histopathology; and to determine the correlation between AAA WS and AAA progression.

Public Health Relevance

Abdominal aortic aneurysms (AAA) enlarge over time and lead to sudden rupture and death in up to 90% of patients. Currently, AAA diameter > 5.5 cm is the criteria for surgical or endovascular aneurysm repair. However, it is a poor predictor of AAA rupture. Aortic wall stiffness (WS) is a fundamental biomechanical parameter that reflects the structural integrity of normal and aneurysmal aortic tissue. Aortic magnetic resonance elastography (AMRE) is a novel non-invasive technique to spatially estimate the stiffness of the aorta. The overall goal of this project is to validate AMRE-derived stiffness against both mechanical testing and histopathology; and that AMRE-derived stiffness will improve our understanding of AAA pathogenesis and provide superior prognostic information compared to aortic diameter.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL124096-02
Application #
8966558
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Danthi, Narasimhan
Project Start
2014-11-14
Project End
2020-04-30
Budget Start
2015-11-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Ohio State University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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