Nuclear Magnetic Resonance Contrast Agents Research Articles

Study of folate receptor-targeted macromolecular gadolinium complex tumor contrast agent

Targeted drug delivery can improve efficacy and reduce dose, so targeted drug delivery is a very ideal diagnostic imaging approach, and it is necessary to develop magnetic resonance imaging contrast agents with targeted effects. In this study, nuclear magnetic resonance contrast agent folic acid-chitosan/chitosan-diethylenetriaminepentaacetic acid-gadolinium nanoparticles (FA-CS/CS-DTPA-Gd NPs) was combined with folic acid (FA) group modified chitosan (CS) and diethylenetriaminepentaacetic acid-gadolinium complex (DTPA-Gd) modified chitosan. FA-CS/CS-DTPA-Gd NPs were characterized by fourier transform spectroscopy (FT-IR), nuclear magnetic resonance (1H NMR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro magnetic properties, cytotoxicity, and targeting to HeLa tumor cells of the nanoparticles were al so evaluated. The results showed that the prepared FA-CS/CS-DTPA-Gd NPs had uniform spheroid shape with particle size of 120.12 ± 1.29 nm; they had good magnetic properties with relaxation rate of 7.5 mM−1·s−1, which was 2.5 times that of DTPA-Gd; they had good in vitro cellular MR imaging and cell safety and could specifically target folic acid-overexpressing tumor cells. The results showed that nanoparticles could be used as targeted magnetic resonance imaging contrast agents in medical diagnostic imaging pathways.

Paramagnetic nanoparticles as nuclear magnetic resonance contrast agents in sandstone: Importance of nanofluid-rock interactions

Nuclear magnetic resonance has been applied in well logging to investigate pore size distribution with high resolution and accuracy based on the relaxation time distribution. However, due to the heterogeneity of natural rock, pore surface relaxivity, which links relaxation time and pore size, varies within the pore system. To analyze and alter pore surface relaxivity, we saturated Boise sandstone cores with positively charged zirconia nanoparticle dispersions in which nanoparticles can be adsorbed onto the sandstone pore wall, while negatively charged zirconia nanoparticles dispersions were used as a control group to provide the baseline of nanoparticle retention due to nonelectrostatic attraction. We have performed core flushing with deionized water, pure acid, and alkali with different pH values; compared properties of zirconia nanoparticles before and after exposure to Boise sandstone; analyzed the portion of zirconia nanoparticles retained in the rock; altered pore surface relaxivity; and linked the adsorbed nanoparticle concentration on the pore surface to the modified surface relaxivity. Our work has indicated that after two pore volumes of core flooding, there was approximately 1% of negatively charged nanoparticles trapped in the Boise sandstone core, whereas approximately 8%–11% of positively charged nanoparticles was retained in the Boise sandstone cores. Our results indicated that besides van der Waals attraction, electrostatic attraction was the driving force for retention of nanoparticles with a positive surface charge in sandstone cores. The attachment of nanoparticles onto sandstone surfaces changed the mineral surface relaxivity. Exposure to acidic or strong alkaline conditions increased the Boise sandstone surface relaxivity. After contact with Boise sandstone, the nanoparticles themselves exhibited increased relaxivity due to interactions between nanoparticles dispersion and mineral surface under different pH conditions.

Miniaturized, biopsy-implantable chemical sensor with wireless, magnetic resonance readout.

Biopsy is an important diagnostic tool for a broad range of conditions. Cancer diagnoses, for example, are confirmed using tissue explanted with biopsy. Here we demonstrate a miniaturized wireless sensor that can be implanted during a biopsy procedure and return chemical information from within the body. Power and readout are wireless via weak magnetic resonant coupling to an external reader. The sensor is filled with responsive nuclear magnetic resonance (NMR) contrast agents for chemical sensitivity, and on-board circuitry constrains the NMR measurement to the contents. This sensor enables longitudinal monitoring of the same location, and its simple readout mechanism is ideal for applications not requiring the spatial information available through imaging techniques. We demonstrated the operation of this sensor by measuring two metabolic markers, both in vitro and in vivo: pH in flowing fluid for over 25 days and in a xenograft tumor model in mice, and oxygen in flowing gas and in a rat hind-limb constriction experiment. The results suggest that this in vivo sensing platform is generalizable to other available NMR contrast agents. These sensors have potential for use in biomedicine, environmental monitoring and quality control applications.

Characterizing Transport and Sorption in Ion-Specific Resin Columns Using Nuclear Magnetic Resonance (NMR) Imaging

The goal of this work is to assess the physical transport properties of Gd through an ion exchange column while determining the sorption properties of the resin. By coupling the physical transport with the chemical sorption, further insight into the behavior of the ion exchange resin can be gained. NMR imaging provides a powerful, non-destructive, means to extract spatial information from complex systems on a near real-time basis. An important example is liquid flow through granular media. With the use of a chemically reactive NMR contrast agent, the chemical speciation can be traced along the physical flow path of the granular media. In this study, trivalent gadolinium (Gd 3+ ) was selected based on its chemical similarity to typical high-level waste components, 241 Am and 244 Cm, and for its paramagnetic contrasting abilities in NMR experiments. NMR imaging results of flow experiments are provided showing a characteristic flow phenomena and resin column loading profiles. ICP-AES data are provided to show resin ion exchange capacities (IECs) and breakthrough curves. The use of NMR imaging with a Gd 3+ tracer will lead to a better understanding of the transport and sorption properties of these ion-specific resins. This technique can be applied to other complex flow systems such as environmental transport.

Relaxivities of different superparamagnetic particles for application in NMR tomography

The development of nuclear magnetic resonance (NMR) imaging technique as a clinical diagnostic modality has prompted the need for a new class of pharmaceuticals, so-called magneto-pharmaceuticals. These drugs must be administered to a patient in order to (1) enhance the image contrast between normal and diseased tissue and/or (2) indicate the status of organ functions or blood flow. A number of different agents have been suggested as potential NMR contrast agents, most of which is highly paramagnetic. Superparamagnetic particles represent an alternative class of NMR contrast agents that usually referred to as T2 or T∗2 contrast agents, opposed to T1 agents such as paramagnetic chelates. Because of their large permanent dipole moments these agents are able to relax neighbouring nuclei faster than paramagnetic ions. The synthesis and measurements of the transverse R2 and longitudinal R1 relaxivities of some ferro-, ferri- and superparamagnetic particles’ suspensions are presented.

Gadolinium labeled pharmaceuticals as potential mri contrast agents for liver and biliary tract

AbstractThree gadolinium‐labeled compounds, potential nuclear magnetic resonance (NMR) imaging contrast agents for liver and biliary tract, were studied: 1 Gd‐DISIDA, 2( Gd‐DTPA‐Liposomes, and 3) Gd‐DTPA dihexadecylamide (Gd‐diamide). In each case, “Carrier Added” Gd‐153 with specific activity of about 5uCi/mg was used. Each labeled compound was evaluated in experimental animals. Gd‐DISIDA proved unsatisfactory because of in vivo instability. Gd‐DTPA‐Liposomes demonstrated strong toxic effects probably due to pulmonary embolism when large amounts of this compound was administered intravenously. Gd‐diamide showed good uptake in the hepatocytes with subsequent excretion into the biliary tract. Several rabbits were imaged in a 0.6T NMR imaging system before and after injection of Gd‐diamide. Pulse sequences were chosen that would yield T1‐weighted images and permit calculation of T1 relaxation times. This compound produced significant shortening of the T1 relaxation times of the liver and observable increase in intensity on the T1‐weighted images. Gd‐diamide shows promise as potential NMR contrast agent for liver and biliary tract imaging.

Effects of the operating magnetic field on potential NMR contrast agents

Paramagnetic metal ions have shown promise as contrast agents for nuclear magnetic resonance (NMR) imaging. Their ability depends upon modification of the relaxation times ( T 1 and T 2) through dipolar interactions. These interactions cause the effectiveness of the agents to be sensitive to the operating magnetic field. Studies are presented of the operating field dependence (frequency dispersion) of two metal-chelate complexes, Gd +3-ethylenediamine-tetraacetate (EDTA) and Mn +2-EDTA, in a physiologically balanced electrolyte solution. Inversion recovery experiments were performed on two concentrations of each metal-chelate complex at five resonant frequencies. The frequency dispersion curves were similar in appearance for those of the corresponding aqueous solutions. The Mn +2 complex showed no unusual concentration effects. The Gd +3 complex showed an unexpected concentration dependence in the dispersion behavior. This is attributed to a difference in the dipolar correlation time between the two solutions. With its unique correlation time in electrolyte solutions, predictions of relaxation rate changes in studies in vivo may be easier for the Mn +2-EDTA complex.

Nuclear magnetic resonance contrast agents for proton imaging

Nuclear magnetic resonance contrast agents for proton imaging

Cardiovascular toxicity and tissue proton T1 response to manganese injection in the dog and rabbit

Paramagnetic substances that shorten proton T1 relaxation time have promise as nuclear magnetic resonance (NMR) contrast agents. The cardiovascular toxicity and tissue T1 response to 0.01-0.1 mM/kg intravenous doses of MnCl2 in rabbits and dogs were studied. There were dose-dependent changes in cardiac electrophysiology and arterial blood pressure consistent with the calcium-blocking properties of manganous ion. There were also dose-dependent and organ-specific changes in tissue proton T1. The sensitivity of organ T1 was expressed as the dose of manganese required to shorten the normal T1 by 50%. Liver, kidney, and heart were most sensitive, while skeletal muscle and adipose tissue were insensitive. MnCl2 is an effective NMR contrast agent, but its toxicity may be excessive for clinical use.

Work in progress: potential oral and intravenous paramagnetic NMR contrast agents.

The potential use of paramagnetic compounds as nuclear magnetic resonance (NMR) contrast agents was examined in vitro. The T1 relaxation times for serial dilutions of Cu2+, Cr3+, Fe3+, and Mn2+ ions in saline, gadolinium oxalate (a potential oral contrast agent) in suspension, and chromium EDTA (a potential intravenous contrast agent) in solution were determined. The effect on T1 of increasing the concentration of oxygen in solution was also examined. The relative magnitude of the decrease in T1 was, as expected, proportional to both the concentration of the paramagnetic substance and its effective magnetic moment. Thus NMR has the potential to detect differences in tissue oxygenation. By incorporating paramagnetic metal ions into insoluble compounds or stable complexes, toxicity can be dramatically reduced while maintaining a significant paramagnetic effect. Highly insoluble paramagnetic compounds or stable paramagnetic ion complexes can thus be utilized as effective NMR contrast agents with significantly diminished toxicity.