The assessment of the Plaque at RISK by non-invasive (molecular) imaging and modelling (ParisK): Validation of imaging techniques with histology

The possibility of the identification of the risk of rupture of a carotid
plaque will have tremendous impact in clinical decision making. Firstly in
symptomatic patients with a 30-69% stenosis, who are currently not operated
upon according to the current guidelines, identification of the risk of rupture
plaque could identify patients who have a high risk of recurrent stroke, and
would, therefore, benefit of carotid intervention, such as endarterectomy or
stent placement. This could potentially prevent a substantial number of
strokes. Secondly, in all symptomatic patients with a 70-99% stenosis carotid
intervention should be considered, according to the guidelines. However, only
one out of six patients with a 70-99% stenosis benefits from a carotid
intervention. Identification of patients with a high risk of a recurrent stroke
would reduce the number of unnecessary interventions substantially. Hence, a
diagnostic imaging test with high accuracy for recurrent stroke prediction has
tremendous clinical impact in patients with carotid artery disease.
A vulnerable plaque is considered to have a large necrotic core, a thin fibrous
cap, the presence of inflammatory cells, intraplaque haemorrhage and/or
neovascularisation (vasa vasorum).
Previous studies have evaluated the use of imaging to assess carotid plaque
vulnerability, mostly showing a good correlation between imaging and histology
and/or clinical characteristics. However, they have focused on single
modalities (magnetic resonance imaging [MRI], mutidetector-row computed
tomography [MDCT], ultrasonography [US] or transcranial Doppler [TCD]), and
have used relatively small cohorts. So far, only 2 studies investigated the
validation of 3.0 Tesla MRI in detection of the characteristics of the
vulnerable plaque. One of these studies is a clinical case report with one
single patient. The other study compared 1.5 Tesla MRI with 3.0 Tesla MRI but
didn*t compare the results with histology.
Regarding, transcranial Doppler, several studies have been performed using
microembolic signals (MES) as a marker of embolic activity and the relation
with different clinical endpoints (stroke, TIA, functioning after surgery).
Mackinnon investigated the relevance of prolonged measurements in symptomatic
and asymptomatic patients. He showed that is worth detecting embolies during
more than one hour.
Given the studies mentioned above, we will perform a validation study in
symptomatic patients with carotidstenosis (n=50), who are scheduled for carotid
endarterectomy (CEA). Participating patients will undergo a 3.0 Tesla MRI of
the carotid atherosclerotic plaque, dual energy CT, ultrasound and TCD
registration for emboli detection in the middle cerebral artery during 4 hours
at least one day prior to the surgery. During surgery, the carotid
endarterectomy specimen will be collected and supervised by members of the
pathology research laboratory. The data obtained from the imaging will be
compared with the histological findings; especially focussing on the
characteristics of the vulnerable plaque.

Primary
- MRI: correlation between neovascularisation in carotid atherosclerotic
plaque characteristics assessed by dynamic 3.0 Tesla MRI and carotid
atherosclerotic plaque at histology.
- CT: correlation between size of lipid-rich-necrotic-core in dual-energy CT
and histology and between neovascularisation in carotid atherosclerotic plaque
characteristics assessed by perfusion CT and carotid atherosclerotic plaque at
histology.
Secondary
- MRI: correlation between volume of LRNC, fibrous cap status, and volume of
calcifications in carotid atherosclerotic plaques visualised by MRI and carotid
atherosclerotic plaques at histology.
- Ultrasound: correlation between deformation pattern and plaque composition
and volume of LRNC at histology.
- TCD: relation between number of recorded MES and fibrous cap status.

Validation study

The side effects of the MRI contrast agent (Gadovist) are rare amongst others
nauseau (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, dyspnoea, flushing, hives, generalized
itching, oral dryness, facial redness, sensation of heat, skin disorder and
aggravated nausea (for each, 0.01%). 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 Gadovist; one patient had a
severe anaphylactoid 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. To minimize the risk of contrast-induced nefropathy,
patients with a renal clearance of less than 30 mL/min/1.73 m2 will not receive
the MR contrast agent.
The radiation dose of an MDCT examination is approximately 9.4 mSv. The CT
contrast agent (Ultravist 300) is associated with a low rate of side effects.
The most reported side effects are heat sensation (1.14%) and nausea (0.52%).
To minimize the risk of contrast-induced nefropathy, patients with a renal
clearance of less than 60 mL/min/1.73 m2 will not undergo the MDCT scan.