Alex Vesey

Project Title

Molecular Imaging in Carotid Atherosclerosis

Funding

The PhD is funded by a British Heart Foundation Project Grant (£251,525) and a Chest Heart and Stroke Projecy Grant (£50,722)

Supervisor

Professor David E Newby and Dr Marc R Dweck

Project Summary

Atherosclerosis is a very common health problem that can lead to fatal or disabling heart attacks and strokes. On many levels, it remains an incompletely understood illness.

Until relatively recently, the only way of assessing the severity of, or risk posed by, atherosclerosis was to measure the degree to which it stenosed a particular blood vessel. This method only tells part of the story; we now know that frequently the 'culprit area' of atherosclerosis that causes the heart attack or stroke isn't necessarily stenotic ¬ i.e. stenosis is a poor biomarker of plaque risk or major adverse cardiovascular event prediction. As such, there is a pressing need to identify more sophisticated techniques of assessing disease in order that people who are at higher risk of heart attack or stroke can be identified early and offered appropriate preventative treatment.

Techniques that provide this extra information could also significantly shorten the time it takes to get new treatments and drugs to market by providing a faster and more cost¬-effective way of assessing these treatments early in their development. Furthermore, in exploring new techniques that reflect more accurately what is going on within atherosclerosis in the body, deeper insight into the condition will be gained. This will in turn lead to the development of new treatments.

PET/CT scans and iron nanoparticle (USPIO) enhanced MRI scans are two such techniques that demonstrate particular promise. These scanning methods not only provide more information about the composition and architecture of the atherosclerosis but can provide data about the processes (at the chemical and cellular level) that underlie the disease.

Inflammation and calcification (deposits of calcium) are two biological processes that are known to be very important in the genesis of atherosclerosis. PET/CT and USPIO enhanced MRI can detect these processes.

Most strokes and mini¬strokes are associated with a carotid artery stenosis. If a patient with transient ischaemic attack, retinal ischaemia or stroke has a carotid stenosis they are normally offered an endarterectomy. This scenario affords a ideal opportunity to explore and validate new scanning techniques.

I propose to explore the feasibility and value of using PET/CT (using 18F-¬Fluorodeoxyglucose and 18F-¬Fluoride;¬ two radio tracers tracers known to highlight inflammation and calcification) and USPIO enhanced MRI to assess atherosclerosis. We will do this by scanning patients who are due to undergo endarterectomy. We will then be able to define what these imaging modalities are revealing at the genetic and the cellular level by performing gene expression and immunohistochemical analysis.