Metabolic Imaging in Carotid Atherosclerosis "MICA"

Recruiting

Phase N/A Results N/A

Trial Description

Hardening of the arteries (atherosclerosis) is a common disorder that causes heart attacks and strokes. PET CT and contrast-enhanced MRI scans are two new ways of assessing atherosclerosis. The investigators propose to perform PET CT and MRI scans on patients with hardening of the neck arteries due to undergo surgery to remove the hardened areas. The investigators will then be able to compare the hot spots found on these scans with what the investigators can see in the removed specimens under the microscope in the laboratory. This will give investigators insight into the value of PET CT and MRI as tools for assessing atherosclerosis. It will also provide the investigators with new information relating to the underlying processes that give rise to atherosclerosis and will pave the way for the future development of new treatments.

Detailed Description

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.

Conditions

Interventions

  • USPIO (ferumoxytol)-enhanced MRI scan Other
    Intervention Desc: Two separate MRI scans will form this intervention. A baseline scan followed by an infusion of USPIO (ferumoxytol), followed by another MRI scan.
    ARM 1: Kind: Experimental
    Label: Carotid Endarterectomy
    Description: Patients due to undergo carotid endarterectomy for symptomatic carotid artery stenosis will undergo an 18F-Fluoride PET/CT, an 18F-Flurodeoxyglucose PET/CT and a USPIO (ferumoxytol)-enhanced MRI scan (2 MRI scans).
  • 18f-Fluoride PET/CT scan Radiation
    ARM 1: Kind: Experimental
    Label: Carotid Endarterectomy
    Description: Patients due to undergo carotid endarterectomy for symptomatic carotid artery stenosis will undergo an 18F-Fluoride PET/CT, an 18F-Flurodeoxyglucose PET/CT and a USPIO (ferumoxytol)-enhanced MRI scan (2 MRI scans).
  • 18F-Flurodeoxyglucose PET/CT scan Radiation
    ARM 1: Kind: Experimental
    Label: Carotid Endarterectomy
    Description: Patients due to undergo carotid endarterectomy for symptomatic carotid artery stenosis will undergo an 18F-Fluoride PET/CT, an 18F-Flurodeoxyglucose PET/CT and a USPIO (ferumoxytol)-enhanced MRI scan (2 MRI scans).

Trial Design

  • Observation: Cohort
  • Perspective: Prospective
  • Sampling: Non-Probability Sample

Trial Population

Patients referred for carotid endarterectomy for symptomatic carotid artery stenosis.

Outcomes

Type Measure Time Frame Safety Issue
Primary The Standardized Uptake Value (SUV) for 18F-Fluoride of the ipsilateral carotid artery 1-2 days after PET/CT scan No
Secondary The SUV of 18F-Flurodeoxyglucose on PET/CT of the ipsilateral carotid artery 1-2 days after PET/CT scan No
Secondary A correlation between the ipsilateral carotid SUV of 18F-Flurodeoxyglucose and tissue markers of inflammation and apoptosis. Approximately 1 month after PET/CT scan No
Secondary A correlation between ipsilateral carotid SUV of 18F-Fluoride and the gene expression characteristics of excised plaque. Approximately 1 month after the PET/CT scan No
Secondary A correlation between the ipsilateral carotid SUV of 18F-Fluoride and tissue markers of apoptosis and calcification. Approximately 1 month after the PET/CT scan No
Secondary 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. 1-2 days after MRI scan No
Secondary A correlation between the ipsilateral carotid USPIO uptake and tissue markers of inflammation and apoptosis. 1 month after MRI scan No
Secondary A correlation between the ipsilateral carotid USPIO uptake and gene expression characteristics of excised atheroma. 1 month after the MRI scan No
Secondary Define a model describing the kinetics of 18F-NaF uptake in carotid atheroma. 1 week after the 18F-Fluoride PET/CT scan No
Secondary The ipsilateral carotid radioactivity, arterial blood radioactivity and whole blood fluoride concentration measured over time During the 18F PET/CT scan No

Biospecimen Retention:Samples With DNA - Blood and excised carotid atheroma

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