Abdominal aortic aneurysms (AAA) are common and can be life-threatening if they progress to rupture. They have been reported in 5% of older men and account for over 15,000 deaths per year. Basic vessel dimensions are currently the primary imaging measurement used clinically to risk-stratify patients. But there is more to the story than dimensions. Wall stress estimated with computational modeling may better predict growth and rupture than diameters. Growth is often not continuous, and instead marked by periods of rapid growth followed by quiescence. Small series report that unrelated surgical procedures can precipitate AAA rupture. These findings suggest that episodic and heterogeneous inflammatory processes in concert with adverse hemodynamics are important for the progression of AAA disease. The complexity of aortic disease is more fully revealed with new functional imaging techniques than with conventional anatomic analysis alone. While AAA has been extensively studied, the mechanisms of disease progression have not been fully elucidated. If better understood, the management of patients with small AAAs (< 5.5cm) could be significantly improved. Many of these aneurysms can be followed safely with a long screening interval of 2-3 years, but some may progress to rupture. Identifying this subset would greatly streamline the surveillance imaging of the millions of patients with AAA. On the other hand, the majority of AAAs never rupture, and identifying low risk patients could help better manage resources and subject only those patients at truly elevated risk to intervention. Aortic wall inflammation can be evaluated with the MRI contrast agent ferumoxytol, which has macrophage- selective properties on delayed imaging. MRI also offers a unique and comprehensive assessment of aortic hemodynamics. Blood flow imaging with time-resolved, 3D phase-contrast MRI (4D Flow) allows quantification of key secondary vascular parameters including turbulence and wall shear stress (WSS). Cine Displacement Encoding with Stimulated Echos (DENSE) can quantify regional stretch differences experienced by the vessel wall. Computational modeling based on MRI volumetric data can be used to calculate wall stress. The goal of our study is to uncover important inflammatory changes and adverse hemodynamics that are not addressed with current imaging, and use them to predict disease progression. We seek to meaningfully advance the assessment of risk in patients who do not meet current intervention thresholds and improve outcomes by refining surveillance imaging regimens and decisions regarding early intervention for AAAs.

Public Health Relevance

Abnormal blood flow patterns and inflammation have been shown to cause disease of blood vessels, but are not currently studied in the routine evaluation of patients. With innovative new imaging techniques, we aim to study how aberrant flow patterns and transient inflammation may place patients at substantial risk for potentially life-threatening vascular disease. We will target a very common vascular abnormality, abdominal aortic aneurysm or the pathologic dilation of the central artery in the belly, which effects 5% of the population over 55 years old.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL123759-01A1
Application #
8836341
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Danthi, Narasimhan
Project Start
2015-01-01
Project End
2018-12-31
Budget Start
2015-01-01
Budget End
2015-12-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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Zhu, Chengcheng; Haraldsson, Henrik; Kallianos, Kimberly et al. (2018) Gated thoracic magnetic resonance angiography at 3T: noncontrast versus blood pool contrast. Int J Cardiovasc Imaging 34:475-483
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Zhu, Chengcheng; Tian, Bing; Leach, Joseph R et al. (2017) Non-contrast 3D black blood MRI for abdominal aortic aneurysm surveillance: comparison with CT angiography. Eur Radiol 27:1787-1794
Vasanawala, Shreyas S; Nguyen, Kim-Lien; Hope, Michael D et al. (2016) Safety and technique of ferumoxytol administration for MRI. Magn Reson Med 75:2107-11
Zhu, Chengcheng; Haraldsson, Henrik; Faraji, Farshid et al. (2016) Isotropic 3D black blood MRI of abdominal aortic aneurysm wall and intraluminal thrombus. Magn Reson Imaging 34:18-25
Ordovas, Karen Gomes; Keedy, Alexander; Naeger, David M et al. (2016) Dilatation of the ascending aorta is associated with presence of aortic regurgitation in patients after repair of tetralogy of Fallot. Int J Cardiovasc Imaging 32:1265-72
Krishnan, Kapil; Ge, Liang; Haraldsson, Henrik et al. (2015) Ascending thoracic aortic aneurysm wall stress analysis using patient-specific finite element modeling of in vivo magnetic resonance imaging. Interact Cardiovasc Thorac Surg 21:471-80

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