title: Kinetic analysis of superparamagnetic iron oxide nanoparticles in the liver of body-temperature-controlled mice using dynamic susceptibility contrast magnetic resonance imaging and an empirical mathematical model.
abstract: The purpose of this study was to develop a method for analyzing the kinetic behavior of superparamagnetic iron oxide nanoparticles (SPIONs) in the murine liver under control of body temperature using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and an empirical mathematical model (EMM). First, we investigated the influence of body temperature on the kinetic behavior of SPIONs in the liver by controlling body temperature using our temperature-control system. Second, we investigated the kinetic behavior of SPIONs in the liver when mice were injected with various doses of GdCl3, while keeping the body temperature at 36°C. Finally, we investigated it when mice were injected with various doses of zymosan, while keeping the body temperature at 36°C. We also investigated the effect of these substances on the number of Kupffer cells by immunohistochemical analysis using the specific surface antigen of Kupffer cells (CD68). To quantify the kinetic behavior of SPIONs in the liver, we calculated the upper limit of the relative enhancement (A), the rates of early contrast uptake (α) and washout or late contrast uptake (β), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum change of transverse relaxation rate (ΔR2) (ΔR2(max)), the time to ΔR2(max) (Tmax), and ΔR2 at the last time point (ΔR2(last)) from the time courses of ΔR2 using the EMM. The β and Tmax values significantly decreased and increased, respectively, with decreasing body temperature, suggesting that the phagocytic activity of Kupffer cells is significantly affected by body temperature. The AUC, ΔR2(max), and ΔR2(last) values decreased significantly with increasing dose of GdCl3, which was consistent with the change in the number of CD68-positive cells. They increased with increasing dose of zymosan, which was also consistent with the change in the number of CD68-positive cells. These results suggest that AUC, ΔR2(max), and ΔR2(last) reflect the number of Kupffer cells. In conclusion, we presented a method for analyzing the kinetic behavior of SPIONs in the liver using DSC-MRI and EMM, and investigated the influence of body temperature, GdCl3, and zymosan using body-temperature-controlled mice. The present study suggests that control of body temperature is essential for investigating the kinetic behavior of SPIONs in the liver and that our method will be applicable and useful for quantifying the responses of Kupffer cells to various drugs under control of body temperature.
authors: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: murase@sahs.med.osaka-u.ac.jp.
authors: Kenya
authors: K
authors: Murase
authors: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Purapan
authors: P
authors: Assanai
authors: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Hiroshige
authors: H
authors: Takata
authors: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Nozomi
authors: N
authors: Matsumoto
authors: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Shigeyoshi
authors: S
authors: Saito
authors: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Motoko
authors: M
authors: Nishiura
mesh_terms: D000818:Animals; D001831:Body Temperature; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans / Q000493:pharmacokinetics*; D007089:Image Enhancement; D008099:Liver / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008962:Models, Theoretical; D053758:Nanoparticles
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides
keywords: Body temperature; GdCl(3); Kupffer cells; Phagocytic activity; Superparamagnetic iron oxide nanoparticles; Zymosan