Imaging and quantification of inflammation in atherosclerotic plaques using positron emission tomography

The work presented in this thesis addresses some of the unresolved issues surrounding the use of PET for identifying and quantifying inflammation in atherosclerotic plaques. Six main questions were posed at the beginning the thesis. Firstly, does plaque FDG truly correlate with the degree of inflammation? Secondly can in-vivo FDG-PET imaging distinguish between inflamed and non-inflamed lesions in a small animal model of atherosclerosis? Thirdly, can the combination of FDG-PET and magnetic resonance (MR) imaging help in the assessment of “culprit” lesions in the carotid circulation in patients who have suffered a stroke? Fourthly, does the limited spatial resolution of PET lead to significant error (a phenomenon called partial volume error) when quantifying plaque FDG uptake in human carotid arteries? Fifthly, how reproducible is FDG-PET when it comes to quantifying FDG uptake in plaques. And finally, does PK11195, a novel synthetic receptor ligand, bind to macrophages and if so can it be used as an alternative to FDG for identifying highly inflamed plaques. The results presented in this thesis confirm a strong correlation between FDG uptake and the degree of macrophage infiltration in atherosclerotic plaques, thus supporting the use of FDG-PET as a technique for quantifying plaque inflammation. In-vivo quantification of plaque FDG uptake was found to be feasible in humans, is highly reproducible, and in combination with MR imaging could potentially be used to help assess and manage patients with atherosclerosis affecting large vessels such as the carotid artery. However, the partial volume effect can lead to significant quantification error, and needs to be taken into account when using this technique. Finally, although encouraging ex-vivo results were seen, there is currently no evidence to suggest that radiolabelled PK11195 is taken up into atherosclerotic plaques in-vivo. However further investigation is needed before ruling out the use of PK11195 for in-vivo imaging of plaque inflammation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo