Predictive value of Magnetic Resonance Imaging (MRI), positron emission tomography (PET), and microemboli detection for stroke

Patients with a moderate to severe carotid atherosclerotic plaque are at risk
for stroke and this risk increases with increasing degree of stenosis.
Subsequently, clinical trials showed that carotid endarterectomy in symptomatic
patients with a carotid artery stenosis of 70-99% is highly beneficial, whereas
the beneficial effect of surgery in patients with a 50-69% stenosis is not yet
clear. The risk of a major stroke in the latter group is about 10% in the first
year after symptoms, while the risk of a major stroke or surgical death within
30 days of surgery is about 7% (ECST trial). A clear beneficial effect of
surgery in the 30-69% stenosis group might be found in a sub-group of patients
whom are at greater risk for stroke after a TIA or minor stroke. Definition of
this sub-group might be achieved by plaque characterization, since rupture of a
vulnerable plaque is the main cause of stroke due to carotid artery stenosis.
Important aspects of vulnerable plaques are a large lipid/necrotic core,
inflammation, and embolization. Recently, we have shown that we can quantify
these different aspects of plaque vulnerability in vivo: the size of the
lipid/necrotic core with high-resolution MRI, the presence of inflammation with
18F-FDG PET, and the amount of microembolization with transcranial doppler
ultrasound. The novel approach of the present project is to investigate whether
one or a combination of the above mentioned imaging techniques enable to define
patients in the 30-69% stenosis group with an increased risk to develop stroke.
Future studies could then investigate whether these patients will profit from
carotid endarterectomy or stenting.
To achieve this objective, we aim to image 263 symptomatic patients with a
30-69% carotid stenosis with high-resolution MRI, 18F-FDG PET, and microemboli
detection with transcranial Doppler ultrasound. The patients will be followed
up for a period of at least one year. The imaging findings will be correlated
with clinical end-points (TIAs, minor/major stroke, silent infarct as detected
as a change on FLAIR MRI after one year).
In summary, we expect that this project will provide an unique dataset which
will show that high-resolution MRI, 18F-FDG PET, and microembolic detection, or
a combination of these techniques, enable the definition of a sub-group of
patients in the symptomatic 30-69% stenosis group with an increased stroke
risk. Future studies will then be warranted to investigate whether these
patients will profit from carotid endarterectomy or stenting.

Primary:
To investigate whether high-resolution MRI, 18F-FDG PET, and microemboli
detection, or a combination of these techniques, enable to identify patients in
the 30-69% stenosis group with an increased stroke risk.
Secondary:
To compare the capabilities of high-resolution MRI, 18F-FDG PET, and
microemboli detection concerning its abilities to define patients in the 30-69%
stenosis group at increased risk for stroke. To assess the influence of patient
positioning in the MRI scanner on results of plaque morphology and composition
analyses (assessment of scan reproducibility). Assessment of scan
reproducibility will be executed in 15 patients with an asymptomatic carotid
artery stenosis.

Prospective study

Patients need to come to the hospital at inclusion, and will then undergo
clinical assessment, an MRI examination (one hour), an 18F-FDG PET examination
(1.5 hours) and microemboli detection with transcranial Doppler ultrasound (one
hour).
After three months, after one year, and then yearly until the end of the study
in 2011, the patients will come back to the hospital for clinical assessment.
Patients will also undergo an MRI examination after one-year follow-up.
Patients will undergo emboli detection with transcranial Doppler ultrasound at
time of inclusion.
To assess the influence of patient positioning in the MRI scanner on results of
plaque morphology and composition analyses, 15 patients with an asymptomatic
carotid artery stenosis will undergo two MRI scans of the carotid artery. The
second MRI scan will be obtained on a different day than the first MRI scan.
Patients with contra-indications for MRI, such as pace-makers, metal implants,
vessel clips, or metal splinters in the eye will be excluded from the study.
The side-effects of the MRI contrast agent (Gd-DTPA) are rare and are amongst
others, headache, nausea, itching, and the appearance of rash. In severe cases
an allergic reaction and shock could occur. In most cases side-effects occur
immediately after contrast injection, and therefore patients will remain in the
hospital for 30 minutes after injection. The administration of the contrast
agents is relatively safe and side-effects are rare.
Patients need to be sober at least six hours before PET scanning. Drinking of
water and use
of medication is allowed.
Diabetic patients using oral medication:
-PET scanning before 14.00 pm: no breakfast, no medication
-PET scanning after 14.00 pm: breakfast before 8.00 am and normal use of
medication.
Subsequently no more eating before scanning.
Insulin-dependent diabetic patients:
-PET scanning before 11.00 pm: no breakfast, no insulin injections
-PET scanning after 11.30: no breakfast, half of the normal insulin dose
-PET scanning after 14.00 m: breakfast before 8.00 am and normal morning
insulin injection. Subsequently no more eating and no more insulin injections
before scanning.
A PET/CT examination exposes a patient to an effective dose of approximately
8.5 mSv. The administration of 18F-FDG does not cause any adverse affects.