Atherosclerosis as an inflammatory diseasehas many implications for the radiologist. Firstly, a goodunderstanding of the disease process can improve both the imaging and the identification of the vulnerable plaque. Secondly, research into the basic science of the disease may yield important gains for the endovascular treatment of atherosclerosis.
Imaging of vulnerable plaque
The current 'gold standard' of assessing atherosclerosis, X-ray angiography, has many weaknesses.Unfortunately, X-ray angiography only demonstrates flow in the lumen of a blood vessel and may not be able detect atherosclerosis in an artery which has undergone remodelling. As plaque rupture can occur at any stage of the disease, even inlesions in which luminal size is preserved, X-ray angiography is not the ideal modality for imaging the vulnerable plaque. The imaging of a vulnerable plaque is the subject of much research, and can be subdivided into three broadcategories; (i) direct plaque imaging; (ii) temperature change; and (iii) imaging of metabolites.
Direct Plaque Imaging
The research onplaque imaging is concentrated on ultrasound- and magnetic resonance imaging(MRI). The use of intravascular ultrasound(IVUS) allows that classification of plaques into soft, fibrous, or calcified(5) (Figure 1). The presence of a softplaque appears to be associated with a higher risk of adverse cardiovascular events(5). However, the clinical use of IVUS is limited because of its invasive, time consuming and expensive nature.
MRI allows the non-invasive characterisation of the fibrous cap and lipid core of the atherosclerotic plaque (Figure 2) (6,7). Indeed, there is good correlation between carotid MRI and histological examination findings. In addition, the finding of intraplaque lipid can be related to high levels of the pro-inflammatory cytokine CD40L, a molecule which has been linked to plaque instability and cardiovascular risk(7).
Temperature Change
A endovascular-catheter mounted thermistor has been developed to detect subtle changes of temperature in an atherosclerotic artery(8). The premise behind this modality is that an inflamed plaque would have a greater temperature than the surrounding normal vessel. Indeed, a higher temperature difference in the atherosclerotic artery appears to be related to the clinical severity of the disease.
Imaging of metabolites
This rapidly progressing field provides the most promise for the imaging of the vulnerable plaque and is almost exclusively based on the use of radiolabelled molecules which bind to- or are taken up by the atherosclerotic plaque. Obviously, these molecules should have rapid clearance from the bloodstream in order to achieve a high signal-to-noise ratio. An example ofone of these moleculesis [18-F]-fluorodeoxyglucose(18-FDG)(9). 18-FDG is a positron-emitting glucoseanalogue which is taken up but not metabolised by cells. Rudd et al have shown that 18-FDG uptake is higher in symptomatic carotid atheromas than asymptomatic lesions and that the 18-FDG uptake could be localised to the macrophages in the plaque(Figure 3).
Treatment of Atherosclerosis: From Bedside to Bench and Back Again
The realisation that atherosclerosis is an inflammatory disease has already yielded great clinical benefits(e.g. in the prevention of post-stenting coronary artery stenosis). The deployment of coronary artery stents and consequent vessel wall injury is associated with thrombotic and inflammatory responses(10). The inflammatory response results in the infiltration of the vessel wall by leukocytes. The release of various cytokines by leukocytes and platelets results in the proliferation and migration of SMCs into the neointima, with consequent in-stent restenosis. Indeed, there is a correlation between the degree of the initial inflammatory response post-coronary angioplasty, as measuredby CRP andmonocyte chemoattractant protein-1,and the propensity towards stent restenosis(10).
The subsequent laboratory observation that sirolimus ('Rapamycin'), a potent anti-inflammatory drug initially developed as an anti-rejection drug for kidney transplantation, is capable of inhibiting SMC migration stimulated research into sirolimus-eluting stents(10). Recent clinical trials have shown that the use of sirolimus-eluting stents can virtually eliminate in-stent restenosis.
More recently, it has been shown that angioplasty of lower limb blood vessels is associated with a large increase in plasma CD40L levels (Figure 4) (11). Apart from its effects on arterial restenosis, the rise in CD40L may have implications for the progression of atheroma elsewhere in the vascular tree. Therefore, there may bea rolefor theuse of anti-inflammatory agents inperipheralarterial angioplasty.Indeed,preliminary results from the SIROCCO trial show that theremay be some promise in the use of sirolimus-eluting stents for peripheral artery angioplasty(12).