Magnetic Resonance Imaging Using Ultrasmall Superparamagnetic Particles of Iron Oxide to Predict Clinical Outcome in Patients Under Surveillance for Abdominal Aortic Aneurysms

Background: Ruptured aortic aneurysms are the thirteenth commonest cause of death in the United Kingdom. Surgical intervention to prevent rupture is considered when the risk of rupture outweighs the risk of procedural complications. There is a major unmet clinical need to develop a better method of identifying patients at risk of rupture and death that goes beyond simple ultrasound measurement of aneurysm. In a preliminary proof-of-concept study, we have recently demonstrated that magnetic resonance detection of mural uptake of ultrasmall superparamagnetic particles of iron oxide (USPIOs) identifies abdominal aortic aneurysms with a 3-fold higher growth rate. Research Design: Prospective observational cohort study. Study Population: Patients with abdominal aortic aneurysms with anteroposterior diameter >40 mm. Planned Interventions: 3T magnetic resonance scan before and after administration of 4.0 mg/kg of USPIOs. Outcome Measures: The abdominal aortic aneurysm of each subject will be imaged with an ultrasound scanner and a 320-multidetector computed tomography scanner with contrast enhancement. Subjects will be followed up every 6 months with clinical and ultrasound scanning as part of the clinical surveillance programme. At 2 years, a repeat computed tomography scan will be performed to assess three-dimensional growth of the aneurysm. Biomechanical stresses of the aneurysm will be assessed by finite element analysis and computational modeling. Assessment and Follow-up: The primary end-point of the study will be the composite of aneurysm rupture or need for surgical repair. Secondary end-points will include aneurysm growth rate as well as the individual rates of aneurysm rupture, aortic aneurysm repair and aneurysm-related mortality. Growth rate will be assessed by both ultrasound and computed tomography. Reproducibility will be assessed in a subgroup of randomly selected patients (n=40). Sample Size: At 80% power and 2-sided P<0.05, 228 patients with abdominal aortic aneurysms will be needed to detect a 20% absolute difference in the primary end-point assuming a 2-year event rate of 50% in those with mural USPIO uptake and 30% in those without. Statistical Analysis: Differences in event rates will be assessed using a binomial test for proportions. Growth rates will be compared using 2-sample t-test or non-parametric equivalent as appropriate. Using an appropriate regression model, we will investigate whether mural uptake of USPIOs is an independent predictor of aneurysm growth. Project Timetables: Following the initial 6-month set up phase, patients will be recruited from our ongoing surveillance programme (>500 suitable patients) over an 18-month period and followed up for up to 36 months. Data analysis, presentation and publication will be undertaken in the final 6 months.