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Shigeyoshi Saito,1 Mana Tsugeno,1 Daichi Koto,1 Yuki Mori,2 Yoshichika Yoshioka,2 Satoshi Nohara,3 Kenya Murase11Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, 2Biofunctional Imaging Lab, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan; 3The Nagoya Research Laboratory, Meito Sangyo Co, Ltd, Kiyosu, Aichi, JapanPurpose: Magnetic resonance imaging (MRI) using contrast agents like superparamagnetic iron oxide (SPIO) is an extremely versatile technique to diagnose diseases and to monitor treatment. This study tested the relative importance of particle size and surface coating for the optimization of MRI contrast and labeling efficiency of macrophages migrating to remote inflammation sites.Materials and methods: We tested four SPIO and ultrasmall superparamagnetic iron oxide (USPIO), alkali-treated dextran magnetite (ATDM) with particle sizes of 28 and 74 nm, and carboxymethyl dextran magnetite (CMDM) with particle sizes of 28 and 72 nm. Mouse macrophage RAW264 cells were incubated with SPIOs and USPIOs, and the labeling efficiency of the cells was determined by the percentage of Berlin blue-stained cells and by measuring T2 relaxation times with 11.7-T MRI. We used trypan blue staining to measure cell viability.Results: Analysis of the properties of the nanoparticles revealed that ATDM-coated 74 nm particles have a lower T2 relaxation time than the others, translating into a higher ability of MRI negative contrast agent. Among the other three candidates, CMDM-coated particles showed the highest T2 relaxation time once internalized by macrophages. Regarding labeling efficiency, ATDM coating resulted in a cellular uptake higher than CMDM coating, independent of nanoparticle size. None of these particle formulations affected macrophage viability.Conclusion: This study suggests that coating is more critical than size to optimize the SPIO labeling of macrophages. Among the formulations tested in this study, the best MRI contrast and labeling efficiency are expected with ATDM-coated 74 nm nanoparticles.Keywords: ultrasmall superparamagnetic iron oxide, cultured mouse macrophage cells, surface coating, particle size, MRI

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

Keiko Tsuchiya1, Norihisa Nitta1, Akinaga Sonoda1, Ayumi Nitta-Seko1, Shinichi Ohta1, Hideji Otani1, Masashi Takahashi1, Kiyoshi Murata1, Katsutoshi Murase2, Satoshi Nohara2, Kenichi Mukaisho31Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, 2The Nagoya Research Laboratory, Meito Sangyo Co, Ltd, Kiyosu, Aichi, 3Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, JapanAbstract: The biodynamics of ultrasmall and small superparamagnetic iron oxide (USPIO and SPIO, respectively) particles that were injected intraperitoneally into 36 C57BL/6 mice were investigated chronologically. Their distribution was studied histologically at six time points by measuring iron-positive areas (µm2) in organ sections stained with Prussian blue. The uptake of the differently sized particles was also compared by cultured murine macrophages (J774.1). Iron-positive areas in the liver were significantly larger in the mice injected with USPIO than those injected with SPIO at the first three time points (P < 0.05). The amount of USPIO in the lung parenchyma around the airway was larger than that of SPIO at four time points (P < 0.05); distribution to the lymph nodes was not significantly different. The amount of iron was significantly larger in SPIO- than USPIO-treated cultured cells (P < 0.05). In conclusion, it is suggested that intra peritoneally injected USPIO particles could be used more quickly than SPIO to make Kupffer images of the liver and that both agents could help get lymph node images of similar quality.Keywords: USPIO, SPIO, contrast agent, biodistribution, histology

Diversity and community structure of fishes were studied in three neighbouring tributaries of the Mekong River in Thailand, namely the Mun, Songkhram and Gam Rivers. The rivers are located in the same ecoregion but have contrasting levels of both hydrological regulations and mitigation measures; the Mun River has a hydropower dam with a fish ladder and sluice gates that are opened during the wet season each year, the Gam River has several irrigation dams with a fish ladder at each dam site, and the Songkhram River has no dams along its river course. A total of 124 freshwater fish species were sampled in these rivers from August 2009 to June 2010. Overall species richness was highest in the Songkhram River (112), followed by the Mun (97) and Gam (54) Rivers. Average per site species richness was also significantly different among rivers but not among sampling months. Abundance–biomass comparison plots revealed considerably overlapping distributions of these two metrics from the dry to early rainy seasons in the Songkhram River and, to a lesser extent, in the Mun River. Fish assemblage data were classified into six clusters with similar community structure. Fish assemblages in the Gam River constituted a single cluster, while those in the other two rivers formed multiple clusters depending on the sampling season. The results of the cluster analysis are discussed in relation to the dominance of the three migration guilds (white, black, and grey fishes) of the Mekong River fishes. The effectiveness of the mitigation measures was determined to be limited in alleviating adverse impacts of dams in these tributaries of the Mekong River. [ABSTRACT FROM AUTHOR]