Non-Specific Zn2+ Ion Sensing Using Ultrasmall Gadolinium Oxide Nanoparticle as a Magnetic Resonance Imaging Contrast Agent.

The gadolinium oxide (Gd2O3) nanoparticles are well-known potential candidates for a positive magnetic resonance imaging (MRI) contrast agent owing to their large longitudinal water proton relaxivity (r1) value with r2/r1 ratio close to one (r2 = transverse water proton relaxivity). In addition they may be used to sense metal ions because their r1 and r2 values can be altered in the presence of metal ions. This may allow us to study metabolic processes involving metal ions and to diagnose disease related to abnormal concentrations of metal ions in the body in a non-invasive way. In this study ultrasmall Gd2O3 nanoparticles were for the first time applied to non-specifically sense Zn2+ ions in aqueous solution. We explored this by measuring r1 and r2 values in the presence of Zn2+ ions in solution.

Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application.

A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd(3+) ((8)S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy(3+) ((6)H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd(3+) and Dy(3+) and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.

Potential dual imaging nanoparticle: Gd2O3 nanoparticle.

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26-38 s(-1) mM(-1) and r2/r1 = 1.4-1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

Synthesis of nanoparticle CT contrast agents: in vitro and in vivo studies.

Water-soluble and biocompatible D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles were synthesized for the first time to be used as x-ray computed tomography (CT) contrast agents. Their average particle diameters were 3.2 ± 0.1 and 2.8 ± 0.1 nm for D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray attenuation. In vivo CT images were obtained after intravenous injection of an aqueous sample suspension of D-glucuronic acid coated Na2WO4 nanoparticles, and positive contrast enhancements in the kidney were clearly shown. These findings indicate that the nanoparticles reported in this study may be promising CT contrast agents.

Ligand-size dependent water proton relaxivities in ultrasmall gadolinium oxide nanoparticles and in vivo T1 MR images in a 1.5 T MR field.

The dependence of longitudinal (r1) and transverse (r2) water proton relaxivities of ultrasmall gadolinium oxide (Gd2O3) nanoparticles on the surface coating ligand-size was investigated. Both r1 and r2 values decreased with increasing ligand-size. We attributed this to the ligand-size effect. In addition the effectiveness of d-glucuronic acid-coated ultrasmall Gd2O3 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents was confirmed by measuring the in vitro cytotoxicity and using in vivo T1 MR images in a mouse in a 1.5 T MR field.

Water-soluble d-glucuronic acid coated ultrasmall mixed Ln/Mn (Ln = Gd and Dy) oxide nanoparticles and their application to magnetic resonance imaging.

Ultrasmall lanthanide oxide nanoparticles are promising materials as new magnetic resonance imaging (MRI) contrast agents because of their appreciable longitudinal (r1) or transverse (r2) water proton relaxivities at ultrasmall particle diameters. Two systems of d-glucuronic acid coated ultrasmall Ln/Mn (Ln = Gd and Dy) oxide nanoparticles with an average particle diameter of 2.0 nm were explored. The d-glucuronic acid coated ultrasmall Gd/Mn oxide nanoparticles showed strong positive contrast enhancements in 1.5 tesla T1 MR images while the d-glucuronic acid coated ultrasmall Dy/Mn oxide nanoparticles showed appreciable negative contrast enhancements in 1.5 tesla T2 MR images, proving their potential as T1 and T2 MRI contrast agents, respectively.

Mixed lanthanide oxide nanoparticles as dual imaging agent in biomedicine.

There is no doubt that the molecular imaging is an extremely important technique in diagnosing diseases. Dual imaging is emerging as a step forward in molecular imaging technique because it can provide us with more information useful for diagnosing diseases than single imaging. Therefore, diverse dual imaging modalities should be developed. Molecular imaging generally relies on imaging agents. Mixed lanthanide oxide nanoparticles could be valuable materials for dual magnetic resonance imaging (MRI)-fluorescent imaging (FI) because they have both excellent and diverse magnetic and fluorescent properties useful for dual MRI-FI, depending on lanthanide ions used. Since they are mixed nanoparticles, they are compact, robust, and stable, which is extremely useful for biomedical applications. They can be also easily synthesized with facile composition control. In this study, we explored three systems of ultrasmall mixed lanthanide (Dy/Eu, Ho/Eu, and Ho/Tb) oxide nanoparticles to demonstrate their usefulness as dual T2 MRI-FI agents.

Surface coated Eu(OH)3 nanorods: a facile synthesis, characterization, MR relaxivities and in vitro cytotoxicity.

The water-soluble and biocompatible D-glucuronic acid coated Eu(OH)3 nanorods (average thickness x average length = 9.0 x 118.3 nm) have been prepared in one-pot synthesis. The D-glucuronic acid coated Eu(OH)3 nanorods showed a strong fluorescence at approximately 600 nm with a narrow emission band width. A cytotoxicity test by using DU145 cells showed that D-glucuronic acid coated Eu(OH)3 nanorods are not toxic up to 100 microM, making them a promising candidate for biomedical applications such as fluorescent imaging. The minimum Eu concentration needed for a conventional confocal imaging was estimated to be approximately 0.1 mM. Therefore, D-glucuronic acid coated Eu(OH)3 nanorods can be applied to fluorescent imaging. However, a very tiny magnetization of approximately 1.2 emu/g at room temperature and at an applied field of 5 tesla was observed. As a result, very small r1 and r2 water proton relaxivities were estimated, implying that surface coated Eu(OH)3 nanorods are not sufficient for MRI contrast agents.

Brain activation patterns of motor imagery reflect plastic changes associated with intensive shooting training.

Evidence from previous studies has suggested that motor imagery and motor action engage overlapping brain systems. As a result of this observation that motor imagery can activate brain regions associated with actual motor movement, motor imagery is expected to enhance motor skill performance and become an underlying principle for physical training in sports and physical rehabilitation. However, few studies have examined the effects of physical training on motor imagery in beginners. Also, differences in neural networks related to motor imagery before and after training have seldom been studied. In the current study, using functional magnetic resonance imaging (fMRI), we investigated the question of whether motor imagery can reflect plastic changes of neural correlates associated with intensive training. In fact, motor imagery was used in this study as a tool to assess the brain areas involved in shooting and involved in learning of shooting. We discovered that use of motor imagery resulted in recruitment of widely distributed common cortical areas, which were suggested to play a role in generation and maintenance of mental images before and after 90 h of shooting training. In addition to these common areas, brain activation before and after 90 h of shooting practice showed regionally distinct patterns of activity change in subcortical motor areas. That is, basal ganglia showed increased activity after 90 h of shooting practice, suggesting the occurrence of plastic change in association with gains in performance and reinforcement learning. Therefore, our results suggest that, in order to reach a level of expertise, the brain would change through initial reinforcement of preexistent connections during the training period and then use more focused neural correlates through formation of new connections.

Paramagnetic dysprosium oxide nanoparticles and dysprosium hydroxide nanorods as T2 MRI contrast agents.

We report here paramagnetic dysprosium nanomaterial-based T(2) MRI contrast agents. A large r(2) and a negligible r(1) is an ideal condition for T(2) MR imaging. At this condition, protons are strongly and nearly exclusively induced for T(2) MR imaging. The dysprosium nanomaterials fairly satisfy this because they are found to possess a decent r(2) but a negligible r(1) arising from L + S state 4f-electrons in Dy(III) ion ((6)H(15/2)). Their r(2) will also further increase with increasing applied field because of unsaturated magnetization at room temperature. Therefore, MR imaging and various physical properties of the synthesized d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles (d(avg) = 3.2 nm) and dysprosium hydroxide nanorods (20 × 300 nm) are investigated. These include hydrodynamic diameters, magnetic properties, MR relaxivities, cytotoxicities, and 3 tesla in vivo T(2) MR images. Here, MR imaging properties of dysprosium hydroxide nanorods have not been reported so far. These two samples show r(2)s of 65.04 and 181.57 s(-1)mM(-1), respectively, with negligible r(1)s at 1.5 tesla and at room temperature, no in vitro cytotoxicity up to 100 µM Dy, and clear negative contrast enhancements in 3 tesla in vivo T(2) MR images of a mouse liver, which will be even more improved at higher MR fields. Therefore, d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles with renal excretion can be a potential candidate as a sensitive T(2) MRI contrast agent at MR field greater than 3 tesla.

A facile synthesis, in vitro and in vivo MR studies of d-glucuronic acid-coated ultrasmall Ln2O3 (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles as a new potential MRI contrast agent.

A facile one-pot synthesis of d-glucuronic acid-coated ultrasmall Ln(2)O(3) (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles is presented. Their water proton relaxivities were studied to address their possibility as a new potential MRI contrast agent. We focused on the d-glucuronic acid-coated ultrasmall Dy(2)O(3) nanoparticle because it showed the highest r(2) relaxivity among studied nanoparticles. Its performance as a T(2) MRI contrast agent was for the first time proved in vivo through its 3 T T(2) MR images of a mouse, showing that it can be further exploited for the rational design of a new T(2) MRI contrast agent at high MR fields.