Monitoring plaque composition: is it worthwile?

In the current issue of the International Journal of Cardiovascular Imaging, Worthley et al. performed a study in New Zealand White rabbits that were fed a 0.2% cholesterol-containing diet for 9 months [1]. At the end of this period a group of rabbits continued having this diet (progression group) for 6 months and a group of rabbits received a normal rabbit diet for 6 months (regression group). At the start of the experiment all rabbits underwent aortic denudation from the aortic arch to the iliac bifurcation by a Fogarty embolectomy catheter passing four times through the lumen from the aortic arch to the iliac bifurcation while inflated.

Using ¹⁸fluoro-deoxyglucose positron emission tomography (¹⁸FDG-PET) the authors imaged the macrophages in the aortic plaques at two moments i.e. at the end of the common 9 months period of 0.2% cholesterol-containing diet, and 6 months later at the end of the progression or regression period. Immediately prior to ¹⁸FDG-PET imaging, aortic localization was defined by cardiovascular magnetic resonance imaging (CMR). Thirty minutes after intravenous administration of ¹⁸FDG, a 30 minute emission scan was obtained. Uptake of ¹⁸FDG by the aortic wall was expressed as the ratio of aortic uptake/blood pool activity. Per aorta a total of 25 consecutive slices were obtained which were pair-wise analyzed using the images taken at the start and at the end of the period under study. The results demonstrated a progressive increase in aortic ¹⁸FDG uptake in the progression group (from 0.57 to 0.68, P = 0.001) and a decrease of aortic ¹⁸FDG uptake in the regression group (from 0.67 to 0.53, P = 0.0001).

Although these results provide highly significant results despite the low number of rabbits per group (n = 4 in progression and regression groups), the data representing the aortic uptake/blood pool activity obtained before and after the period under study show a broad overlap. Unfortunately, the graphs lack lines between the two values from the same rabbit. Secondly, it is regrettable that the initial values of aortic uptake/blood pool activity of the rabbits in the progression and the regression groups differ from each other, while both groups had the same atherogenic diet for 9 months.

Nevertheless, this study is important for several reasons: first—as a proof of concept -, in vivo ¹⁸FDG-PET imaging of large vascular structures that are subject to an atherogenic stimulus or relieved from an atherogenic stimulus appears feasible; second, since macrophages are primarily responsible for the ¹⁸FDG uptake in the atherosclerotic aortic wall [2, 3], in vivo ¹⁸FDG-PET imaging of a large artery provides information about a major determinant of an unstable plaque i.e. the intra-plaque density of inflammatory cells such as macrophages [4, 5]; and third, the PET technique allows the noninvasive monitoring of relative changes in vascular inflammatory lesions in vivo over longer periods of time.

At an earlier stage, Rudd and coworkers had already reported that in patients with symptomatic carotid atherosclerosis uptake of ¹⁸FDG uptake in symptomatic lesions in the carotid wall was higher by 27% than in contra-lateral asymptomatic lesions [6]. Normal carotid arteries had no measurable ¹⁸FDG uptake at all. In 43 patients who underwent ¹⁸FDG-PET for cancer screening the ¹⁸FDG uptake of the thoracic aorta and/or the carotid arteries were imaged as well. After randomization to either simvastatin or dietary management for 3 months, the simvastatin group—but not the diet group - had less ¹⁸FDG uptake in the aorta and/or carotid arteries compared to the initial uptake data [7]. Thus the well-known anti-inflammatory effect of simvastatin [8, 9] can be monitored by ¹⁸FDG-PET in a non-invasive way in vivo. The technique has to be combined with an imaging technique to visualize the anatomical structures such as CMR or multi-slice computed tomography (CT). As a stand-alone image modality, multi-slice CT is able to characterize lesion size and composition in coronary arteries [10–17], but the inflammatory component of the lesion is not yet identified specifically by this technique. The combination of ¹⁸FDG-PET with CMR or with multi-slice CT would allow imaging lesion size and lesion composition [18–38], particularly with respect to inflammatory cells that determine the vulnerability of the plaque [39–41]. Worthley and co-authors [1] are to be complimented for showing in a low number of relatively small animals changes in macrophage content of plaques in the aortic wall in response to continued cholesterol-containing diet (progression group) and in response to normal diet after 9 months of cholesterol-containing diet (regression group). Research aimed to stabilize plaques would have great benefit from vascular imaging using ¹⁸FDG-PET.