Metabolic Imaging in Carotid Atherosclerosis

Hardening of the arteries (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 narrowed a particular blood vessel. This method only tells part of the story; he investigators now know that frequently the 'culprit area' of atherosclerosis that causes the heart attack or stroke does not necessarily result in narrowing of the blood vessel - i.e. if the investigators only measure narrowness the investigators will miss lots of 'bad' atherosclerosis. As such, there is a pressing need to identify more sophisticated techniques of assessing the 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 USPIO (a kind of tracer) 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 caused by a narrowing in the neck artery. If a patient with mini-stroke or stroke has a narrowing (atherosclerosis) in their carotid artery they are normally offered an operation to remove the atherosclerosis (endarterectomy), the piece of atherosclerosis is then normally discarded. This scenario affords a perfect opportunity to explore new scanning techniques.

The investigators propose to explore the feasibility and value of using PET/CT (using 18F-FDG and 18F-NaF - two tracers known to highlight inflammation and calcification) and USPIO enhanced MRI to assess atherosclerosis. The investigators will do this by scanning patients who have just had a mini-stroke or minor stroke and are due to undergo endarterectomy. The investigators will then be able to define what is going on at the level of the genes and the cells that causes 'hot spots' on CT/PET and MRI.

Inclusion criteria

• Patients with carotid stenosis due to undergo carotid endarterectomy.

Exclusion criteria

• Patients with new stroke and a modified Rankin score >3
• Chronic Kidney Disease with eGFR of <30 mL/min/1.73m2
• Pregnant women
• Poorly controlled diabetes mellitus (HbA1c > 8.5%) or diabetes mellitus requiring insulin
• Prior ipsilateral carotid intervention
• Prior neck irradiation
• Inability to tolerate the supine position
• Participation in the study would result in delay to surgery
• Psychiatric illness/social situations that would limit compliance with study requirements
• Specific contraindications to MRI (e.g. pacemaker)
• History of allergic reaction attributed to ferumoxytol or similar
• Known or suspected iron overload (genetic haemochromatosis or history of multiple transfusions)
• History of allergic reaction attributed to 18F-FDG or 18F-NaF or similar
• History of allergic reaction to iodine or iodine-based contrast media