Abstract Most magnetic materials studied as negative contrast agents for magnetic resonance imaging (MRI) enter the superparamagnetic state with decreasing size of their particles, which is distinguished by thermal fluctuations of particle magnetic moment. In the present study, a novel type of contrast agents based on non-superparamagnetic nanoparticles (nanomagnets) of aluminum-doped epsilon polymorph of Fe2O3 is suggested and used as a model system to elucidate the role of magnetic blocking and other factors in the transverse relaxation of water. Specifically, the dependence of the transverse relaxivity r2 on the magnetic field (0.47–11.75 T), temperature (278−348 K), magnetization, surface modification (silica or citrate) and thickness of silica coating (6−21 nm) is analyzed for the e-AlxFe2-xO3 nanoparticles with x = 0.23 and the median size of 21 nm. These nanoparticles evinced higher magnetization than the undoped material and were in the blocked state in the temperature range under study. Further, irreversible magnetization processes were revealed by SQUID magnetometry in aqueous suspension of coated clusters of magnetic crystallites that resulted in the field dependence of r2. The temperature dependence of r2 was interpreted by the combination of two different regimes – motional averaging and static dephasing regimes. Slow diffusion of water molecules inside the silica shells was suggested to explain only moderate decrease of r2 with increasing the coating thickness. Moreover, the performance of the contrast agent was demonstrated not only in ultra-high-field MRI at 11.75 T but also by imaging in vivo on a mouse model at 1 T. Finally, preliminary evaluation of cytotoxicity on rat mesenchymal stem cells did not reveal any significant effects. Due to their low toxicity and high relaxivity, e-AlxFe2-xO3 nanoparticles present a promising starting material for further biomedical applications involving MRI, multimodal contrast agents and theranostic carriers.

中文翻译：

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ε-AlxFe2-xO3 纳米磁体作为 MRI 造影剂：影响横向弛豫的因素

摘要 作为磁共振成像（MRI）的负造影剂研究的大多数磁性材料随着其颗粒尺寸的减小而进入超顺磁性状态，其特征在于颗粒磁矩的热波动。在本研究中，提出了一种基于 Fe2O3 铝掺杂 epsilon 多晶型的非超顺磁性纳米粒子（纳米磁体）的新型造影剂，并将其用作模型系统，以阐明磁性阻塞和其他因素在横向弛豫中的作用的水。具体而言，分析了横向弛豫率 r2 对磁场（0.47-11.75 T）、温度（278-348 K）、磁化强度、表面改性（二氧化硅或柠檬酸盐）和二氧化硅涂层厚度（6-21 nm）的依赖性对于 x = 0 的 e-AlxFe2-xO3 纳米颗粒。23 和 21 nm 的中值大小。这些纳米颗粒表现出比未掺杂材料更高的磁化强度，并且在所研究的温度范围内处于封闭状态。此外，不可逆的磁化过程通过 SQUID 磁力测定法在磁性微晶涂层簇的水悬浮液中揭示，导致 r2 的场依赖性。r2 的温度依赖性通过两种不同机制的组合来解释 - 运动平均和静态移相机制。水分子在二氧化硅壳内的缓慢扩散被认为只能解释 r2 随着涂层厚度的增加而适度降低。此外，造影剂的性能不仅在 11.75 T 的超高场 MRI 中得到证实，而且在 1 T 小鼠模型上的体内成像也得到了证明。最后，对大鼠间充质干细胞的细胞毒性的初步评估未显示任何显着影响。由于它们的低毒性和高弛豫性，e-AlxFe2-xO3 纳米粒子为进一步的生物医学应用提供了一种有前途的起始材料，包括 MRI、多模态造影剂和治疗诊断载体。