Abstract 592: Atherosclerotic Plaques in the Mouse Aortic Arch as Detected by Lipid-based MR Contrast Agents
Introduction: Atherosclerosis is the main cause of morbidity and mortality in Western societies. It is challenging to determine plaque burden in moving areas like the aortic arch. We quantified atherosclerotic plaques and determined the optimum time curve for in vivo visualization of plaques in the aortic arch of ApoE−/− mice, using lipid-based MR CA compared to a conventional Gd-containing CA using retrospectively gated cine MRI.
Methods: Dotarem®, gadolinium (Gd)-containing NIR664-conjugated micelles and liposomes were applied in 3 groups (n=5) of 10 to 14 months old male ApoE−/− mice. Mice were imaged using a vertical Bruker MRI system (9.4T). The aortic arch was imaged before and after 6 –12 hour intervals for up to 6 days following intravenous injection of Dotarem, micelles or liposomes, using equivalent doses of Gd (50 μmol/kg). Confocal microscopy and immunohistochemistry correlated CA with atherosclerotic plaques.
Results: Heterogeneous contrast enhancement (CE) in the aortic wall was observed within 6 hrs after Dotarem injection. Both micelle- and liposome-injected mice, on the other hand, showed a bi-phasic CE, with a first peak in contrast-to-noise-ratio (CNR) about 12 hours. A 2nd wave was observed with peak CNR (60 –72 hrs). Plasma relaxivity demonstrated was inversely related to aortic CE, suggestive for organ retention of micelles and liposomes, and release ~1.5 days post injection. The lipid-based CAs were found both extra- and intracellular in the plaques. MR signal intensity in the 2nd CE wave after injection was predictive for plaque volume, although not with Dotarem. Organ retention (liver and spleen) is determined to study the biodistribution of Gd to explain the 2nd wave.
Conclusions: Lipid-based CA have a complex biodistribution involving multiple organ systems. Passive uptake of CA shows retention in several plaque components. The optimal imaging window varies between animal models and contrast agents. As the standardly used 24h interval was not nearly optimal we propose to optimize the time course of experiments separately when using new models and CA.
Acknowledgement: supported by the Netherlands Heart Foundation (NHS2006-T106) and DiMi (LSHB-CT-2005–512146).