Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide for abdominal aortic aneurysm: a risk prediction study
Authors: Forsythe Rachael , McBride Olivia , Robson Jennifer , Graham Catriona , Conlisk Noel , Hoskins Peter , Wee Fiona , Newby David 
Published: October 2018

Background
Abdominal aortic aneurysm (AAA) rupture is a common cause of sudden death. Pre-emptive elective surgical repair can prevent aneurysm rupture and be life-saving. Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation using magnetic resonance imaging (MRI) in patients with AAAs. For this reason, USPIO-enhanced MRI represents a promising new technique that could improve risk prediction and better guide surgical intervention.

Objectives
To assess whether or not USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes in patients with AAAs.

Design
A prospective multicentre open-label observational cohort study.

Setting
Three secondary and tertiary care hospitals in Scotland.

Participants
Patients (n = 342) aged > 40 years with a maximum anteroposterior AAA diameter of ≥ 40 mm confirmed by abdominal ultrasonography, and under ultrasonographic surveillance as part of routine clinical care.

Interventions
USPIO-enhanced MRI of AAA.

Main outcome measures
The primary end point was the composite of aneurysm rupture or repair. Secondary outcomes included rate of aneurysm growth, all-cause mortality and aneurysm-related mortality.

Results
Participants (85% male, aged 73.1 ± 7.2 years) had a baseline aneurysm diameter of 49.6 ± 7.7 mm, and USPIO enhancement was identified in 146 participants (42.7%), absent in 191 participants (55.8%) and indeterminate in 5 participants (1.5%). During follow-up (1005 ± 280 days), there were 17 AAA ruptures (5.0%), 126 AAA repairs (36.8%) and 48 deaths (14.0%). Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1 ± 2.5 vs. 2.5 ± 2.4 mm/year; p = 0.0424), although this was not independent of current smoking habits (p = 0.1993). The primary end point (aneurysm rupture or repair) occurred more frequently in participants with USPIO enhancement [69/146 (47.3%) vs. 68/191 (35.6%), difference 11.7%, 95% confidence interval 1.1% to 22.2%; p = 0.0308]: this was similar for each component of rupture (6.8% vs. 3.7%; p = 0.1857) or repair (41.8% vs. 32.5%; p = 0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (p = 0.0275). Baseline AAA diameter (p < 0.0001) and current smoking habits (p = 0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic 0.7935 to 0.7936).

Conclusions
USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with AAAs, and predicts the rate of aneurysm growth and clinical outcome. USPIO-enhanced MRI does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. Larger trials are now needed to explore the prediction of emergent aneurysm events to establish the added benefit of USPIO-enhanced MRI. Comparative outcome studies should determine whether or not using other imaging biomarkers that track alternative disease processes have better predictive capability than USPIO-enhanced MRI.

Trial registration
Current Controlled Trials ISRCTN76413758.

Funding
This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.