Evaluation of atherosclerotic lesions using dextran- and mannan–dextran-coated USPIO: MRI analysis and pathological findings

Keiko Tsuchiya¹, Norihisa Nitta¹, Akinaga Sonoda¹, Ayumi Nitta-Seko¹, Shinichi Ohta¹, Masashi Takahashi¹, Kiyoshi Murata¹, Kenichi Mukaisho², Masashi Shiomi³, Yasuhiko Tabata⁴, Satoshi Nohara<sup>5

1</sup>Department of Radiology, ²Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, ³Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Hyogo, ⁴Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, ⁵Nagoya Research Laboratory, Meito Sangyo, Kiyosu, Aichi, Japan

Abstract: Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO). Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively) by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5) or D-USPIO (n = 5). Two rabbits were the controls. The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2) (n = 1), or 0.8 (dose 3) (n = 3) mmol iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR) of the aortic wall in the same region of interest (ROI) was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05) for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05). With in vitro MRI scans, SNR was significantly lower in rabbits treated with dose 2 of DM-USPIO compared with D-USPIO treatment (P < 0.05), and it tended to be lower at dose 3 (P < 0.1). In conclusion, we suggest that DM-USPIO is superior to D-USPIO for the study of atherosclerotic lesions in rabbits.

Keywords: atherosclerosis, magnetic resonance imaging, contrast media, plaque, mannan–dextran-coated USPIO