Validation of CT Angiography and/or Magnetic Resonance Imaging markers for characterization and quantification of atherosclerosis in the carotid arteries by comparison with surgical specimens.

Atherosclerosis is a systemic disease that may silently affect the entire
arterial tree. Frequently the initial clinical manifestation is stroke,
myocardial infarction or sudden death. Stroke is the third most important cause
of death in the Western world and the leading cause of permanent disability.
Atherosclerotic disease in the carotid bifurcation is in 20-30% of the cases
responsible for ischemic stroke. Since the further understanding of the
pathological mechanism of atherosclerosis advances are being made in imaging
this prevalent disease.
Histopathological studies have shown that the majority of myocardial
infarctions and stroke are due to an atherosclerotic plaque that erodes or
ruptures generating a thromboembolic event at the site or downstream of the
disrupted plaque. Interestingly the majority is mildly-to-moderately stenosed.

Cerebrovascular accidents like transient ischemic attack (TIA) and stroke are
related to the size of the stenosis in the internal carotid artery, in
symptomatic and asymptomatic patients (2-4). However in the past decade, it has
been recognized that plaque vulnerability is much more important than plaque
size for the development of acute events (5). The recognition of the role of
the vulnerable plaque in the development of cardiovascular events provides a
novel opportunity for improved risk assessment.

In the carotid vasculature, high risk or symptomatic plaques are those with a
thin-fibrous cap, intraplaque inflammation or hemorrhage, and a lipid-rich
necrotic core (LRNC). Ultrasound (US) and Computed tomography angiography (CTA)
have established themselves as accurate modalities to assess the presence of
atherosclerotic disease in the carotid bifurcation and grade the severity of
stenosis (6). In addition, due to its inherent superior contrast resolution,
multi-sequence MRI has the potential to identify and measure plaque structure
in symptomatic subjects (lipid, haemorrhage, fibrotic tissue and calcium) in
the carotid arteries and to quantify plaque volume and volume of different
components (7-10). LRNC, as assessed with MRI, is related to the presence and
extent of ischemic cerebral lesions 11. Contrast-enhanced plaque imaging
improves the differentiation of the LRNC from fibrous tissue12-13. In addition
MR images obtained during administration of contrast material can be used to
quantify degree of plaque inflammation. Our aim in this study is to prove the
ability of CT and/or MRI to image the vessel lumen, to assess bloodflow
parameters, different plaque components and plaque morphology of an
atherosclerotic plaque in the carotid arteries. In that case CT and/or MRI
could provide information on plaque vulnerability and the risk of future
events. It could influence therapeutic decisions. Moreover, development of
atherosclerosis can be studied by relating blood flow parameters to plaque
morphology and composition.

The study will be embedded in the Erasmus MC, a single center observational
diagnostic study among 150 patients with acute symptomatic stenosis in the
carotid arteries aged 18 years and older. All patients are planned for carotid
endarterectomy (CEA) at the ErasmusMC. This population who will undergo a
surgical operation is chosen for the reason that it will be possible to relate
the CT or MRI scan with the removed carotid atherosclerotic plaque (gold
standard).

CT Angiography and MRI could provide information on lumen, vessel flow and/or
plaque composition and morphology.

1) Validation of CT angiography and/or MRI markers to identify the different
components of the atherosclerotic plaque in the carotid arteries by comparison
with histologic specimens.
2) Evaluation of plaque development by relating MRI derived flow parameters to
plaque composition and morphology on histology, and by relating plaque
composition to plaque morphology

A single center observational diagnostic study.

There are no risks associated with participation in this study. The total
burden of this study is one MRI examination in patients who are hospitalized
for a CEA.

The side effects of the MRI contrast agent (Gadobutrol) are rare and are
amongst others nausea (0.25%), vomiting (0.05%), urticaria (0.04%), feeling of
warmth, tachycardia, wheals (for each 0.03%), dizziness, itching,
vasodilatation, itchy throat (for each 0.02%) and cough, dyspnea, flushing,
hives, generalized itching, oral dryness, facial redness, sensation of heat,
skin disorder and aggravated nausea (for each, 0.01%)1.

Out of 14 299 patients, two serious ADRs occurred (0.01%), which were
considered by the treating physician to be probable associated with the
administration of adobutrol;
One patient had a severe anaphylactic reaction and the other presented with
itching and swelling in the throat.

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 with a renal clearance (eGFR) of less than 30 mL/min will not receive
the MR contrast agent. There are no other test, examinations or questionnaires.