Potential contrast agents for magnetic resonance imaging

The development ofmagneto-pharmaceuticals plays an important role in the extension of nuclear magnetic resonance into diagnostic medicine. That is the reason why fundamental investigations leading to new insights into NMR contrast agents are presently being considered. The synthesis and the proton relaxation rates of some new contrast agents are presented. The high values ofR ₁, andR ₂ relaxivities of the compounds studied by us are promising for various and novel applications.     

Dilute oral iron solutions as gastrointestinal contrast agents for magnetic resonance imaging; initial clinical experience

Delineation of the gastrointestinal tract in magnetic resonance imaging (MRI) remains a problem. Ferric ammonium citrate is paramagnetic, producing a high MRI signal intensity by virtue of its spin-lattice (T1) relaxation rate enhancement properties. Water is diamagnetic, producing a low MRI signal intensity, especially with short TR and TE times. To compare efficacy for gastrointestinal contrast alteration, ferric ammonium citrate was administered to 18 patients and water was given to 10 patients. Spin-echo imaging at 0.35T was performed after administration of these agents. Ferric ammonium citrate produced high signal intensity within the esophagus, stomach, duodenum, and small intestine that aided in the differentiation of the gastrointestinal tract from adjacent tumors, vessels, and viscera. Delineation of the gut wall was superior using ferric ammonium citrate compared to that produced by water. Delineation of the margins of the pancreas, liver, and kidney from adjacent gastrointestinal tract was also better with ferric ammonium citrate. Optimal distinction between bowel and fat was better with water. Longer TE times (75 to 200 ms) may allow improved contrast between gut and intrabdominal fat using ferric ammonium citrate.     

Microbubbles containing gadolinium as contrast agents for both phase contrast and magnetic resonance imaging

Portal vein imaging is an important method for investigating portal venous disorders. However, the diagnostic requirements are not usually satisfied when using single imaging techniques. Diagnostic accuracy can be improved by combining different imaging techniques. Contrast agents that can be used for combined imaging modalities are needed. In this study, the feasibility of using microbubbles containing gadolinium (MCG) as contrast agents for both phase contrast imaging (PCI) and magnetic resonance imaging (MRI) are investigated. MCG were made by encapsulating sulfur hexafluoride (SF₆) gas with gadolinium and lyophilized powder. Absorption contrast imaging (ACI) and PCI of MCG were performed and compared in vitro. MCG were injected into the main portal trunk of living rats. PCI and MRI were performed at 2 min and 10 min after MCG injection, respectively. PCI exploited the differences in the refractive index and visibly showed the MCG, which were not detectable by ACI. PCI could facilitate clear revelation of the MCG‐infused portal veins. The diameter of the portal veins could be determined by the largest MCG in the same portal vein. The minimum diameter of clearly detected portal veins was about 300 µm by MRI. These results indicate that MCG could enhance both PCI and MRI for imaging portal veins. The detection sensitivity of PCI and MRI could compensate for each other when using MCG contrast agents for animals.     

Evaluation of nonionic nitroxyl lipids as potential organ-specific contrast agents for magnetic resonance imaging.

Considering their intrinsic properties of accumulation in the hepatic tissue, we have synthesized nitroxyl-containing lipids as potential organ-specific contrast agents for magnetic resonance imaging (MRI). Their resistance to reduction by ascorbate and in liver homogenates, and their relaxivity in different media were investigated and compared to those of free carboxyl-Proxyl (3-carboxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl) and Tempamaine (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl). With respect to the reduction rates by ascorbate, the lipid derivatives show the same well-known order of reactivity as carboxy-Proxyl and Tempamine, the five-membered nitroxyls being more stable than the six-membered compounds. However the binding of the piperidinoxyl compounds to the fatty acids confers to those lipid derivatives a markedly increased stability. Similarly, in liver homogenates, the nitroxyl lipids remained unchanged more than 20 min, contrarily to carboxy-Proxyl and Tempamine. The measurements of spin-lattice relaxation time (T1) in biological media have demonstrated a higher relaxivity of nitroxyl lipids, which can be related to their interaction with proteins. Tested in vivo, one of the synthesized compounds (0.75 mmol/kg) produced an enhancement of 44 +/- 12% of the hepatic signal 5 min after intraportal injection in T1-weighted images. The potential applicability of the other nitroxyl lipids as contrast agents for MRI was limited in the in vivo studies by an unexpected toxicity. Work is currently in progress to improve the therapeutic index of the present class of nitroxyl lipids.     

High-pressure NMR study of water exchange on magnetic resonance imaging contrast agents

Abstract

The knowledge of water exchange reaction mechanism in aqueous solutions of Gd³⁺ polyaminocarboxylates is important for the understanding of the relatively slow water exchange rates measured for these complexes. Variable ressure measurements show a change of mechanism from associatively activated on [Gd(H₂O)₈]³⁺ and [Gd(PDTA)(H₂O₂)₂]^? to probably limiting dissociative on the MRI contrast agents [Gd(DOTA)(H₂O)]^?, [Gd(DTPA)(H₂O)]^2? and [Gd(DTPA-BMA)(H₂O)].     

Characterisation of magnetic resonance imaging (MRI) contrast agents using NMR relaxometry

ABSTRACT

This contribution describes the use of Fast Field-cycling relaxometry (FFC-NMR) for the characterisation of Gd(III)- and Mn(II)-based contrast agents for MRI. Through a series of selected examples, we analyse the role of different structural and dynamic parameters on ¹H relaxivity and on the shape of the ¹H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles. The amplitude and shape of the profiles is affected by the number of water molecules coordinated to the metal ion, the water exchange rate, the rotational correlation time of the complex and the relaxation of the electron spin. As a result, ¹H NMRD profiles represent a powerful tool for the understanding of the properties of MRI contrast agent candidates at the molecular level.     

Optimizing tissue contrast in magnetic resonance imaging

Magnetic resonance imaging demands that tissue contrast and signal-to-noise advantages be sought in each component of the imaging system. One component of magnetic resonance imaging in which contrast and signal-to-noise ratios are easily manipulated is in the choice of pulse sequences and interpulse delay times. This article provides a general method for determining the best choices of interpulse delay times in pulse sequences and applies that method to saturation recovery, inversion recovery, and spin-echo sequences. Saturation recovery and inversion recovery sequences with rephasing pulses, and tissues with unequal hydrogen densities are considered. Optimization of pulse sequences is carried out for the two distinct cases of (a) a fixed number of sequence repetitions and (b) a fixed total imaging time. Analytic expressions are derived or approximate expressions are provided for the interpulse delay times that optimize contrast-to-noise ratios in each pulse sequence. The acceptable range of interpulse delay times to obtain reasonable contrast using each pulse sequence is discussed.     

Ingested manganese chloride as a contrast agent for magnetic resonance imaging

Solutions of manganese chloride were force-fed to Sprague-Dawley rats. Magnetic resonance (MR) imaging was performed on (a) syringes containing different concentrations of manganese chloride, (b) rats after force feeding and (c) livers excised after sacrifice of the force-fed rats. Imaging was done with a 0.15-T resistive magnet. Multiple pulse sequences were used and T1 values were calculated. The signal intensity and T1 value obtained from a solution depended on the manganese concentration and the pulse sequence employed. At higher concentrations, no signal was produced due to extreme T2 shortening. Absorbed manganese affected the signal intensities and T1 values of the rats' livers. By appropriate selection of manganese concentration and pulse sequence, ingested manganese can serve as a combined gastrointestinal and hepatic MR contrast agent.     

Transport of contrast agents in contrast-enhanced magnetic resonance angiography

Contrast-enhanced magnetic resonance angiography (CEMRA) often appears to display vessels with good resolution, but it does not adequately visualize the throat of a tight stenosis. Image quality in CEMRA is also governed by the timing of contrast injection and data acquisition. We developed a numerical technique to predict the image appearance of a target vessel by taking into account the passage of contrast agent. Experiments were conducted on a phantom with both centric and linear ordering. An effort to prolong the duration in which the contrast passes by employing a double injection technique gives a wider window of opportunity to acquire quality images.