Metabolic Imaging in Carotid Atherosclerosis (MICA)

• The Standardized Uptake Value (SUV) for 18F-Fluoride of the ipsilateral carotid artery [ Time Frame: 1-2 days after PET/CT scan ] [ Designated as safety issue: No ]
  The mean and maximum SUV (using 18F-NaF) of the ipsilateral carotid artery will be calculated and compared to its contra lateral partner. The SUV is a validated quantitative assessment of PET radiotracer uptake.
  
  

• The SUV of 18F-Flurodeoxyglucose on PET/CT of the ipsilateral carotid artery [ Time Frame: 1-2 days after PET/CT scan ] [ Designated as safety issue: No ]
  The mean and maximum SUV (using 18F-Flurodeoxyglucose) of the ipsilateral carotid artery will be calculated and compared to its contra lateral partner.
  
  
• A correlation between the ipsilateral carotid SUV of 18F-Flurodeoxyglucose and tissue markers of inflammation and apoptosis. [ Time Frame: Approximately 1 month after PET/CT scan ] [ Designated as safety issue: No ]
  Sections of excised atheroma that demonstrate uptake of 18F-Flurodeoxyglucose will be subjected to histological examination. A variety of immunohistochemical markers of inflammation and apoptosis will be quantitatively assessed for correlation with the degree of radioligand uptake. Tissue showing no radioligand uptake will be used as control.
  
  
• A correlation between ipsilateral carotid SUV of 18F-Fluoride and the gene expression characteristics of excised plaque. [ Time Frame: Approximately 1 month after the PET/CT scan ] [ Designated as safety issue: No ]
  Sections of excised atheroma that demonstrate uptake of 18F-Fluoride will be subjected to gene expression profiling. Sections of plaque that do not show uptake will be used as controls. The resulting data will be analyzed to explore the variation in gene expression between subjects and between areas of differing radioligand uptake. Genes of particular interest (either identified during expression profiling or selected beforehand) will be further studied using quantitative PCR.
  
  
• A correlation between the ipsilateral carotid SUV of 18F-Fluoride and tissue markers of apoptosis and calcification. [ Time Frame: Approximately 1 month after the PET/CT scan ] [ Designated as safety issue: No ]
  Sections of excised atheroma that demonstrate uptake of 18F-Fluoride will be subjected to histological examination. A variety of immunohistochemical markers of calcification and apoptosis will be quantitatively assessed for correlation with the degree of radioligand uptake. Tissue showing no radioligand uptake will be used as control.
  
  
• The presence or absence of USPIO (ultra-small superparamagnetic particles of iron oxide) uptake on MRI (magnetic resonance image) within the ipsilateral carotid artery compared to its contralateral partner. [ Time Frame: 1-2 days after MRI scan ] [ Designated as safety issue: No ]
  USPIOs are known to accumulate within activated macrophages in inflamed atheroma. This causes a demonstrable drop in T2* signal on MR.
  
  
• A correlation between the ipsilateral carotid USPIO uptake and tissue markers of inflammation and apoptosis. [ Time Frame: 1 month after MRI scan ] [ Designated as safety issue: No ]
  Sections of excised atheroma will be co-stained for USPIO and a variety of immunohistochemical markers of inflammation and apoptosis.
  
  
• A correlation between the ipsilateral carotid USPIO uptake and gene expression characteristics of excised atheroma. [ Time Frame: 1 month after the MRI scan ] [ Designated as safety issue: No ]
  Sections of excised atheroma that demonstrate uptake of USPIO will be subjected to gene expression profiling. Sections of plaque that do not show uptake will be used as controls. The resulting data will be analyzed to explore the variation in gene expression between subjects and between areas of differing USPIO uptake. Genes of particular interest (either identified during expression profiling or selected beforehand) will be further studied using quantitative PCR.
  
  
• The ipsilateral carotid radioactivity, arterial blood radioactivity and whole blood fluoride concentration measured over time [ Time Frame: During the 18F PET/CT scan ] [ Designated as safety issue: No ]
  The kinetics of 18F-Fluoride in atherosclerosis have not yet been defined. Using data from the PET scanner in list mode and regular arterial and venous blood sampling in 20 patients (a subset of the total) we will define a model describing the radiopharmacokinetics of 18F-Fluoride in carotid atheroma.
  
  

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.