Rachael Forsythe

Biography

Miss Rachael Forsythe graduated MBChB from the University of Edinburgh in 2008 and completed Core Surgical Training in Bristol. Following this, she was accepted to the South West London training programme as a speciality registrar in general surgery in 2012. Her interests lie in vascular surgery and she is hoping to transfer to the vascular curriculum in early 2015. She is completing a PhD in the Centre for Cardiovascular Science under the supervision of Professor David Newby (BHF Professor of Cardiology) and Mrs Jennifer Robson (lecturer in surgery) and will subsequently return to complete her clinical surgical training in London.

Project Title

Molecular Imaging in Abdominal Aortic Aneurysm Disease: MRI and PET-CT to Predict Aneurysm Expansion and Rupture.

Funding

The MA3RS study (MRI in AAA to predict Rupture or Surgery) is funded by an MRC EME grant (£2.2 million) The SoFIA3 study (Sodium Fluoride Imaging in AAA) is funded by the CSO (£205,747).

Supervisors

Professor David Newby and Mrs Jennifer Robson

Project Summary

Ruptured abdominal aortic aneurysms (AAA) have a 90% mortality rate but there are currently no accurate methods of establishing the risk of AAA expansion or rupture for an individual patient. The measurement of AAA diameter using ultrasound imaging has traditionally been used to stratify risk of expansion or rupture, based on data from population studies.

Evaluation of AAA rupture risk is currently based on the maximum anteroposterior aneurysm diameter on ultrasound imaging. Surgical intervention is offered when the risk of rupture exceeds the risks associated with repair and is currently offered to patients with AAA >55mm or expansion rate of >1mm/year. However, up to 1 in 5 of ruptured AAAs has a diameter <55mm, whilst many patients have very large aneurysms that never rupture. We also know that AAA expansion occurs in a non-linear and unpredictable manner, which makes risk prediction even more complex.

Aneurysm disease results from a complex interaction between biomechanical and biological processes, including inflammation. These processes affect the aorta in a focal manner, and such focal biological ‘hotspots’ are thought to represent regions of the aortic wall at further risk of expansion and rupture. In addition, calcification is also widely observed in aneurysm disease and co-localises to areas of necrotic inflammation and apoptosis.

Ultra small supra-paramagnetic particles of iron oxide (USPIO) has been used as a ‘smart’ MRI contrast agent to identify areas of mural inflammation. In a pilot study by Jenny Robson et al, this technique has been shown to help identify patients at increased risk of AAA expansion or rupture. Following on from this data, the MA3RS study (MRI in AAA to predict Rupture or Surgery) was established in 2012 to investigate the use of USPIO-enhanced MRI in an observational cohort study of 350 patients with asymptomatic AAA. MA3RS is funded by an MRC EME award and I have taken over as the principle research fellow working on the study to its completion in 2016.

The SoFIA3 study (Sodium Fluoride Imaging in AAA) is investigating the use of PET-CT in predicting AAA expansion. As a sub-study of MA3RS, SoFIA3 aims to recruit 100 patients from the MA3RS cohort. We will explore the use of the radiotracer 18F-NaF to identify areas of active microcalcification in the aneurysm wall. We will investigate these biologically active areas and whether they correspond with established macrocalcification, areas of necrotic inflammation and whether this technique can help predict AAA expansion.