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Page 2 of 10 Mueller et al. Vessel Plus 2018;2:13 I http://dx.doi.org/10.20517/2574-1209.2018.19

plasmatic levels of chemokine RANTES (P = 0.03) and higher levels of ICAM-1 in MES+ patients (P = 0.03). Interestingly
MMP-2 levels were more important in patients with lower TBR values (P = 0.02) and MMP-3 and P-selectin in those
who were MES- (respectively P = 0.001 and P = 0.009).

Conclusion: In the present study, ICAM-1 was associated with the presence of thrombotically active atherosclerotic
plaques, while RANTES mainly correlated with the inflammatory process. MMP-2, MMP-3 and P-selectin levels were
more important in patients with stable plaques.

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Keywords: Carotid plaque, biomarkers of inflammation, microemboli detection, transcranial Doppler, FDG-PET-CT

INTRODUCTION
Inflamed carotid plaques play a key role in the occurrence of distal embolic cerebral infarcts . Intensive
[1-3]
research has been performed in the last few decades aimed at optimizing different imaging modalities with
adequate spatial resolution to precisely analyse the arterial wall morphology, plaque composition, and degree
of local inflammation . Among them, positron emission tomography (PET) using the glucose analogue
[4-6]
18
18 fluoro-2-deoxy-D-glucose ( FDG) as a radiotracer reflecting glycolytic activity has shown promise
for non-invasive functional detection of local inflammation in atherosclerotic plaques and is considered
as an emergent marker of plaque vulnerability . Furthermore, ultrasound-based imaging modalities
[7-9]
demonstrated that the presence of microembolic signals (MES) detected by means of transcranial Doppler
downstream the stenosis is associated with an increased risk of embolic stroke [10-12] .

In the present study we investigated in patients with symptomatic or asymptomatic carotid stenosis the
relationship between FDG-PET-computed tomography (CT), MES and plasmatic biomarkers of inflammation
18
including adhesion molecules, interleukins (ILs), chemokines, cytokines, matrix-metalloproteases (MMP)
and lipoprotein-associated phospholipase A2 (lp-PLA2).

METHODS
We included patients with unilateral symptomatic or asymptomatic carotid disease with 50% to 99% degree
of stenosis according to the ECST criteria. Symptomatic stenosis was defined as any recent (< 6 months)
neurological or retinal deficit, persisting or transient ischemic attack (TIA), which could be plausibly
attributed to the ipsilateral carotid artery. Assessment of clinical parameters was performed upon study
inclusion. Symptomatic patients had a complementary work up including cardiac ultrasound examination
and long duration electrocardiogram for 7 days in order to exclude a cardio-embolic origin of stroke.
Asymptomatic stenosis was defined as no history of recent (within the last 6 months) neurological or retinal
deficit and/or presence of ipsilateral ischemic magnetic resonance imaging (MRI) lesions. All patients gave
their written consent.

18 FDG-PET/CT angiography
All patients underwent FDG-PET-CT with contrast angiography within 2-3 days after admission when
18
symptomatic, and within 10 days after assessment of the diagnosis of carotid stenosis when asymptomatic.
We used a standard protocol as described previously . Analysis of PET-CT was done by two experienced
[13]
investigators (JPW, HM) blinded to the clinical and biological data. The target to background ratio (TBR)
was assessed by dividing the SUVmax of the carotid plaque wherever highest by the average SUVmean of
the jugular veins.

Ultrasound analysis
Standard examination included duplex ultrasound of the carotid arteries (SIEMENS) with assessment of
degree of stenosis according to the ECST criteria , plaque surface morphology and plaque echogenicity.
[14]