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Keiko Tsuchiya1, Norihisa Nitta1, Akinaga Sonoda1, Ayumi Nitta-Seko1, Shinichi Ohta1, Masashi Takahashi1, Kiyoshi Murata1, Kenichi Mukaisho2, Masashi Shiomi3, Yasuhiko Tabata4, Satoshi Nohara51Department 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, JapanAbstract: 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

The concentration of total neopterin in serum and cerebrospinal fluid (CSF) was measured in cases of febrile convulsion, aseptic meningitis and influenza encephalopathy. In febrile convulsion except for exanthem subitum, the concentrations of CSF neopterin (26± 11, Mean±SD, n=6) were all within normal range while those of serum neopterin (66± 20, n=8) were significantly higher (p < 0.05). In aseptic meningitis, on the other hand, the concentrations of CSF neopterin (194± 130, n=13) were significantly higher than those of serum (33±23, n=11, p < 0.05). In influenza encephalopathy, both concentrations of serum neopterin (329±478, n=13) and CSF neopterin(179±131, n=11) were much higher than the control range. Our results indicate that the primary immunoreacting site is the central nervous system (CNS) for aseptic meningitis, the periphery for febrile convulsion except for exanthem subitum and both the periphery and the CNS for influenza encephalopathy. Measurements of neopterin concentrations in CSF as well as in serum may thus constitute an immediate aid for early differentiation of CNS infection from peripheral infection as well as for early detection of viral encephalopathy caused by viruses such as the influenza virus or the human herpes virus 6.