In vivo carotid plaque magnetic resonance imaging using quantitative T2* measurments with USPIO particles: a dose-response study to statin therapy

It is well established that carotid atherosclerotic disease and the resulting plaque tissue composition are associated with thromboembolic complications, namely stroke and transient ischemic attacks [1]. MR studies have sought to identify carotid plaque inflammation using Ultra-small Super-Paramagnetic Iron Oxide (USPIO) contrast agents. Ferumoxtran-10, known commercially as SineremTM (Guerbet, Roissy, France), originally developed to detect metastatic disease in lymph nodes, has since been repeatedly applied to study atherosclerotic carotid plaques [2, 3]. Previous studies that used USPIO contrast-enhancement to measure carotid-plaque inflammation have measured ‘change’ as the relative difference in signal intensity in the plaque normalized to the adjacent sternocleidomastoid muscle. A quadruple inversion recovery (QIR) prepared T2*-weighted spiral sequences has been used to suppress signal from blood over a range of T1 values post-contrast infusion [4]. ‘Change’ appears as a hypo-intensity difference in the post-infusion image relative to the pre-infusion image. A recent phase-I randomized double-blinded dose response trial, known as ATHEROMA [Atorvastatin THeraphy: Effects on Reduction of Macrophage Activity], utilized USPIO-contrast enhancement to investigate the interaction of lowand high-dose statin therapy. The clinical outcomes of this trial have been report separately [5]. The work reports USPIO-inflammation as normalized relative changes in signal intensity using the T2*-weighted spiral sequence. Quantitative issues with this methodology have been discussed [6].