Iron Oxide Magnetic Resonance Imaging for Atherosclerosis Therapeutic Evaluation

Abstract

Multicenter, randomized, placebo-controlled "outcome" trials with long-term follow-up of thousands of patients are currently being used to evaluate new therapies for cardiovascular disease. Owing to improvements in risk factor modifications as well as to the concomitant use of established treatments, such as statins, leading to a drop in clinical event rates, it is projected that the number of patients enrolled in trials may need to be increased to separate the effect of new therapies from those of established ones. Recently, the JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin) study (1) showed the importance of serologic measures of inflammation. These new in-blood See page 2039 markers may, however, be insufficient when used alone as predictive models of mortality and morbidity (2). Several recent cardiovascular trials have opted to use imaging (quantitative coronary angiography, carotid intima media thickness with ultrasonography, coronary intravascular ultrasonography, and so forth) to measure the impact of promising novel therapeutics (3). Validation of these in vivo diagnostic imaging methods may allow for shorter follow-up times and eventually, for smaller patient populations tested.Many imaging technologies focus primarily on changes in luminal size or vessel wall area. New imaging methods that focus on vessel wall composition, and relate to the underlying plaque pathogenesis, may provide useful information not readily available by standard morphometric measurements. For example, noninvasive magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to identify inflammatory changes by monitoring macrophage uptake, a major component of high-risk (vulnerable) plaques.To date, there have been no published studies that show correlations between the dose of prescribed statin and in vivo changes in macrophage distribution. The study by Tang et al. (4) in this issue of the Journal is the first prospective molecular MRI study that tries to correlate the in vivo effects of statin therapy on carotid plaque inflammation, as observed by MRI (5). The study found a significant reduction from baseline in USPIO-enhanced MRI-defined plaque inflammation in the high-dose atorvastatin group at both 6 weeks and at 12 weeks after treatment. Such changes were not observed in the low-dose statin (i.e., atorvastatin 20 mg) group. These findings provide additional in vivo evidence that high-dose statin (i.e., 80 mg) therapy might have a beneficial effect on plaque "stability." Furthermore, these changes in USPIO-defined plaque inflammation could be observed within 6 weeks, a relatively short treatment interval compared to the prolonged periods (years) that are required to observe changes in plaque burden. This study may also indicate that reductions in plaque inflammation may play an important role in the mechanism underlying the early beneficial effects of statins.If adequately validated, USPIO-enhanced MRI met...

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