Contrast-enhanced ultrasound and magnetic resonance imaging for the evaluation of neovascularisation in carotid artery plaques

The process of atherosclerosis usually starts at young age. Gradually, in blood
vessels lesion with lesions with composed of fat, smooth muscle cells and
connective tissue arise. Eventually, these so-called plaques can cause a
decrease of the lumen of a blood vessel. Mostly this does not cause any
clinical symptoms, as long as the blood vessel is not completely obliterated.
However, the layer of connective tissue separating the plaque from the lumen
can rupture, so that the fatty content of the plaque will come in contact with
the blood. This will cause the formation of a thrombus at the place of the
rupture, which can obliterate the lumen. It can also occur that (part) of the
thrombus will propagate and obliterate a smaller vessel. In both cases, the
tissue behind the obliteration will be deprived from blood and oxygen, which
can lead to tissue damage or cell death (infarction). In atherosclerosis of the
carotid arteries, it will cause a TIA, or even worse, a stroke.
Patients who have had a TIA (transient ischemic attack of the brain) or stroke
will undergo a standard ultrasound examination to assess the presence of
atherosclerosis of the carotid arteries. At this examination, the degree of
stenosis will be measured using acoustic waves. If the degree of stenosis is
more than 70%, the vascular surgeon will decide (in consultance with the
patient and the neurologist) to surgically remove the plaque , because of the
high risk of (recurrent) stroke.
However, research has shown that the composition of the plaque may be even more
important than the degree of stenosis which is caused by it; a plaque which
causes only little stenosis may still be very vulnerable. Besides the
accumulation of fat, smooth muscle cells and connective tissue, growth of new
small blood vessels (neovascularisation) often occurs in a plaque.
Neovascularisation may be an important factor contributing to plaque
vulnerability. A standard ultrasound examination cannot depict
neovascularisation in a plaque. An ultrasound examination using a contrast
agent (contrast-enhanced ultrasound), however, may be able to do so. Magnetic
resonance imaging (MRI) has shown to be able to make detailed pictures of the
carotid artery. However, it is still unknown whether both contrast-enhanced
ultrasound and MRI are able to depict neovascularisation in a plaque.

The purpose of this study is to investigate whether contrast-enhanced
ultrasound and/or MRI are able to depict neovascularisation in atherosclerotic
lesions (plaques) of the carotid artery. If contrast-enhannced ultrasound
and/or MRI are able to do so, subsequent studies can investigate whether
patients in whom neovascularisation has been diagnosed (by these imaging
modalities), indeed are at higher risk of developing a stroke. These patients
would then be eligible for extra and/or earlier therapy to prevent a
(recurrent) stroke.

This is a diagnostic study.
Findings of pre-operative contrast-enhanced ultrasound and MRI will be compared
to the results of histopathological analysis of (resected) plaques of the
carotid artery.

Burden
-The length of contrast-enhanced ultrasound is approximately 45 minutes, and
patients will lay on a bed during this examination. The patient will not feel
anything of the imaging procedure.
-During the MRI examination, patients way lay on their back for approximately
45 minutes. This may be inconvenient for patients with back problems. The
patient will not feel anything of the imaging procedure. The MRI scanner will
make a lot of noise during the examination, which can be inconvenient. To
overcome this, patients will use earplugs or earphones. The MRI scanner is a
kind of tube, which is open at he front and at the rear end. Still, some people
may find it inconvenient to lay is such a *tube*.
It will be attempted to plan both examinations (contrast-enhanced ultrasound
and MRI) at the same day. If this is not possible, each of the examinations
will take place on separate days (in consultance with the patient).

Risks
-Contrast-enhanced ultrasound uses acoustic waves which are harmless. Adverse
effects of the contrast agent used (SonoVue) are uncommon, among which headache
and nausea. A rare adverse effect is the occurrence of an allergic reaction and
shock. Therefore, participating patients should remain in the hospital (under
observation) up to half an hour after administration of the contrast agent. At
the site of the injection of the contrast agent, a temporarily sensitive area
may occur, along with some swelling the occurrence of a blue bruise. Very
seldom, an infection occurs at this site.
-MRI does not use ionising radiation and is not dangerous. However, patients
with pacemakers, metallic implants, vascular clips or metallic eye fragments
may not participate in this study. The adverse effects of the MRI contrast
agent (Magnevist) 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 adverse 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. At the site of the injection of the contrast agent,
a temporarily sensitive area may occur, along with some swelling the occurrence
of a blue bruise. Very seldom, an infection occurs at this site.