High-performance Magnetic Resonance Imaging Contrast Research Articles

Gadolinium-Coated Mesoporous Silica Nanoparticle for Magnetic Resonance Imaging.

Magnetic resonance molecular imaging can provide anatomic, functional and molecular information. However, because of the intrinsically low sensitivity of magnetic resonance imaging (MRI), high-performance MRI contrast agents are required to generate powerful image information for image diagnosis. Herein, we describe a novel T 1 contrast agent with magnetic-imaging properties facilitated by the gadolinium oxide (Gd2O3) doping of mesoporous silica nanoparticles (MSN). The size, morphology, composition, MRI relaxivity (r 1 ), surface area and pore size of these nanoparticles were evaluated following their conjugation with Gd2O3 to produce Gd2O3@MSN. This unique structure led to a significant enhancement in T 1 contrast with longitudinal relaxivity (r 1 ) as high as 51.85 ± 1.38 mM−1s−1. Gd2O3@MSN has a larger T 1 relaxivity than commercial gadolinium diethylene triamine pentaacetate (Gd-DTPA), likely due to the geometrical confinement effect of silica nanoparticles. These results suggest that we could successfully prepare a novel high-performance T 1 contrast agent, which may be a potential candidate for in-vivo MRI.

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.

Development of Gd3N@C80 encapsulated redox nanoparticles for high-performance magnetic resonance imaging

As novel magnetic resonance imaging (MRI) contrast agent, gadofullerene encapsulated redox nanoparticles (Gd3NPs) were prepared by encapsulation of Gd3N@C80 in the core of core-shell-type polymer micelles composed of original polyamine with a reactive oxygen species (ROS)-scavenging ability. Because Gd3NPs possess biocompatible PEG shell with a smaller size (ca. 50 nm), they had high colloidal stability in a physiological environment, and showed low cytotoxicity. Specific accumulation of Gd3NPs in a tumor was confirmed in tumor-bearing mice after systemic administration. The tumor/muscle (T/M) ratio of the Gd ion reached five at 7.5 h after the administration. T1-weighted MRI signal enhancement of the T/M ratio increased by 8% at 6 h postinjection of Gd3NPs (Gd dose:14.35 μmol/kg). Although Gd3NPs showed a tendency for extended blood circulation, they did not have severe adverse effects, probably due to the confinement of Gd in a hydrophobic fullerene in addition to the ROS-scavenging capacity of these nanoparticles. In sharp contrast, systemic administration of Gd-chelate nanoparticles (GdCNPs) to mice disrupts liver function, increases leukocyte counts, and destroys spleen and skin tissues. Leaking of Gd ions from GdCNPs may cause such adverse effects. Based on these results, we expect that Gd3NPs is high-performance MRI contrast agents for tumor diagnosis.

Shape-Dependent Relaxivity of Nanoparticle-Based T1 Magnetic Resonance Imaging Contrast Agents.

Gold nanostars functionalized with Gd(III) have shown significant promise as contrast agents for magnetic resonance imaging (MRI) because of their anisotropic, branched shape. However, the size and shape polydispersity of as-synthesized gold nanostars have precluded efforts to develop a rigorous relationship between the gold nanostar structure (e.g., number of branches) and relaxivity of surface-bound Gd(III). This paper describes the use of a centrifugal separation method that can produce structurally refined populations of gold nanostars and is compatible with Gd(III) functionalization. Combined transmission electron microscopy and relaxivity analyses revealed that the increased number of nanostar branches was correlated with enhanced relaxivity. By identifying the underlying relaxivity mechanisms for Gd(III)-functionalized gold nanostars, we can inform the design of high-performance MRI contrast agents.

Iron oxide nanorods as high-performance magnetic resonance imaging contrast agents.

An efficient magnetic resonance imaging (MRI) contrast agent with a high R2 relaxivity value is achieved by controlling the shape of iron oxide to rod like morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of 70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity value of 608 mM(-1) s(-1). The enhanced MRI contrast of nanorods is attributed to their higher surface area and anisotropic morphology. The higher surface area induces a stronger magnetic field perturbation over a larger volume more effectively for the outer sphere protons. The shape anisotropy contribution is understood by calculating the local magnetic field of nanorods and spherical nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical geometry, the induced magnetic field of a rod is stronger and hence the stronger magnetic field over a large volume leads to a higher R2 relaxivity of nanorods.

Interplay between longitudinal and transverse contrasts in Fe3O4 nanoplates with (111) exposed surfaces.

Iron oxide has been developed as either T1 or T2 magnetic resonance imaging (MRI) contrast agents by controlling the size and composition; however, the underlying mechanism of T1 and T2 contrasts in one iron oxide entity is still not well understood. Herein, we report that freestanding superparamagnetic magnetite nanoplates with (111) exposed facets have significant but interactional T1 and T2 contrast effects. We demonstrate that the main contribution of the T1 contrast of magnetic nanoplates is the chemical exchange on the iron-rich Fe3O4(111) surfaces, whereas the T2 relaxation is dominated by the intrinsic superparamagnetism of the nanoplates with an enhanced perturbation effect. We are able to regulate the balance of T1 and T2 contrasts by controlling structure and surface features, including morphology, exposed facets, and surface coating. This study provides an insightful understanding on the T1 and T2 contrast mechanisms, which is urgently needed to allow more sophisticated design of high-performance MRI contrast agents.

Tunable T1 and T2 contrast abilities of manganese-engineered iron oxide nanoparticles through size control.

In this paper, we demonstrate the tunable T1 and T2 contrast abilities of engineered iron oxide nanoparticles with high performance for liver contrast-enhanced magnetic resonance imaging (MRI) in mice. To enhance the diagnostic accuracy of MRI, large numbers of contrast agents with T1 or T2 contrast ability have been widely explored. The comprehensive investigation of high-performance MRI contrast agents with controllable T1 and T2 contrast abilities is of high importance in the field of molecular imaging. In this study, we synthesized uniform manganese-doped iron oxide (MnIO) nanoparticles with controllable size from 5 to 12 nm and comprehensively investigated their MRI contrast abilities. We revealed that the MRI contrast effects of MnIO nanoparticles are highly size-dependent. By controlling the size of MnIO nanoparticles, we can achieve T1-dominated, T2-dominated, and T1-T2 dual-mode MRI contrast agents with much higher contrast enhancement than the corresponding conventional iron oxide nanoparticles.

Facile Solvothermal Synthesis of Mesostructured Fe3O4/Chitosan Nanoparticles as Delivery Vehicles for pH‐Responsive Drug Delivery and Magnetic Resonance Imaging Contrast Agents

We report a facile fabrication of a host-metal-guest coordination-bonding system in a mesostructured Fe3O4/chitosan nanoparticle that can act as a pH-responsive drug-delivery system. The mesostructured Fe3O4/chitosan was synthesized by a solvothermal approach with iron(III) chloride hexahydrate as a precursor, ethylene glycol as a reducing agent, ammonium acetate as a porogen, and chitosan as a surface-modification agent. Subsequently, doxorubicin (DOX), acting as a model drug (guest), was loaded onto the mesostructured Fe3O4/chitosan nanoparticles, with chitosan acting as a host molecule to form the NH2-Zn(II)-DOX coordination architecture. The release of DOX can be achieved through the cleavage of coordination bonds that are sensitive to variations in external pH under weakly acidic conditions. The pH-responsive nature of the nanoparticles was confirmed by in vitro releases and cell assay tests. Furthermore, the relaxation efficiency of the nanoparticles as high-performance magnetic resonance imaging contrast agents was also investigated. Experimental results confirm that the synthesized mesostructured Fe3O4/chitosan is a smart nanovehicle for drug delivery owing to both its pH-responsive nature and relaxation efficiency.

Physicochemical Characterization, and Relaxometry Studies of Micro-Graphite Oxide, Graphene Nanoplatelets, and Nanoribbons

The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn2+ ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents.

Facile solvothermal synthesis of monodisperse Fe3O4 nanocrystals with precise size control of one nanometre as potential MRI contrast agents

A facile solvothermal approach was used to synthesize ultrasmall monodisperse magnetite (Fe3O4) nanoparticles with precise size control of one nanometre, in which iron acetylacetonate [Fe(acac)3] acted as the iron source, n-octylamine as the reductant, and n-octanol as the solvent. By varying the volume ratios of n-octylamine to n-octanol, 4 nm, 5 nm and 6 nm Fe3O4 nanoparticles were obtained. Compared with the popular thermal decomposition methods to Fe3O4 nanoparticles, this solvothermal process, without the need for a N2 atmosphere and reflux conditions, was more convenient. The intrinsic crystallography of the obtained magnetite nanoparticles was characterized by XRD and HRTEM, the particle size, shape, superlattice and self-assembly were observed by TEM, and the surface of nanoparticles was studied by FT-IR and XPS. The magnetic properties of the different particle sizes were measured at room temperature. Furthermore, the relaxation efficiency of three samples as high-performance magnetic resonance imaging contrast agents depending on the particle size was investigated in cetyltrimethyl ammonium bromide (CTAB) aqueous solution.

Superparamagnetic gadonanotubes are high-performance MRI contrast agents

We report the nanoscale loading and confinement of aquated Gd3+n-ion clusters within ultra-short single-walled carbon nanotubes (US-tubes); these Gd3+n@US-tube species are linear superparamagnetic molecular magnets with Magnetic Resonance Imaging (MRI) efficacies 40 to 90 times larger than any Gd3+-based contrast agent (CA) in current clinical use.