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PET/CT for detection of vulnerable carotid artery plaques

Martin Græbe



Vulnerable atherosclerotic plaques are characterized by inflammation and an increased risk of thromboembolic events. Considering carotid artery atherosclerosis and intervention, the current risk stratification of patients with a carotid plaque is based solely on the degree of stenosis. Inflammation within the plaque is not included in the risk profile. Positron emission tomography (PET) using the radionuclide tracer FDG has been suggested to reflect the presence of macrophages in atherosclerotic lesions, and this non-invasive molecular imaging method thus may have a role in future patient risk stratification. The aim of this thesis was to investigate the potential use of PET for detection of the vulnerable atherosclerotic carotid artery plaque.


Methods The thesis presents a prospective evaluation of patients referred to ultrasound investigation of the carotid arteries because of a symptomatic stenosis. All patients were PET/CT scanned and different quantification methods of FDG uptake in both symptomatic plaques and contralateral plaques were calculated. Plaque ultrasound images were recorded and echolucency quantitated by gray scale median (GSM) analysis. Twenty-two patients were included for carotid endarterectomy the day after PET, and excised plaques were investigated using quantitative PCR for molecular gene expression analyses of markers of inflammation and vulnerability. All patients were PET scanned 3 hours after injection of FDG and ten patients were additionally scanned 1 hour after injection of FDG. Our major hypotheses were: 1) that plaque FDG uptake was associated with gene expression of inflammatory markers. 2) That plaque FDG uptake was associated with already known risk markers, using both gene-expression analyses and ultrasound morphology as established risk-factors and 3) that a simple approach to conduct the PET of atherosclerotic plaques could be adopted for future clinical implementation of PET.

Results Plaque gene-expression of the macrophage specific marker CD68 correlated with plaque FDG uptake in the PET scans performed the day before endarterectomy (r=0.71, P=0.02, n=10). Plaque mRNA expression of the inflammatory cytokine Interleukin 18 (IL-18), and the two proteinases Cathepsin K and Matrix Metalloproteinase 9 (MMP-9) were also positively correlated with FDG uptake. In the ultrasound studies, there was a negative correlation between GSM and FDG-uptake (r=-0.56, P<0.0001, n=55). The results showed, that echo-rich plaques tended to show low FDG uptake, whereas echolucent plaques ranged from high to low inflammatory activity as depicted with PET.  Comparisons of 1 and 3 hour PET acquisitions revealed, that using the quantification standard SUVmax results were comparable between the to time points. 

Conclusion PET/CT scanning with the tracer FDG can be used for quantification of inflammatory activity in carotid plaques as determined by CD68 gene expression. Plaque FDG uptake also correlates with other markers of vulnerability and inflammation, as well as with ultrasound echogenicity quantitated by gray scale median. Although a higher target to background activity is found on the PET scan 3 hours after FDG injection compared to early scans, we suggest a simple approach using SUVmax with acquisition at 1 hour after FDG injection as a future clinical routine for PET identification of inflamed carotid plaques.