A rapid dynamic imaging sequence has been developed in which only the 32 phase encoding steps that encode low spatial frequencies are collected for each dynamic image. These are substituted into a previously acquired, 128 x 128 raw data set prior to image reconstruction. In this way the dynamic information is retained while the overall appearance is improved in comparison with images obtained by zero filling to 128 x 128, leading to better qualitative evaluation. The limited k-space sampling means that the technique is most effective for large homogeneous areas of signal change since fine changes in contrast are imperfectly recorded.

ISIGNAL INTENSITY on a magnetic resonance (MR) image is mainly determined by proton density and T1 and T2. Image contrast, described as the difference in signal intensity between two tissues, is dependent on a number of physical parameters and can be altered by changing these parameters. Contrast agents are pharmaceuticals that can accentuate the difference in signal intensity between two adjacent tissue compartments by directly interfering with the proton relaxation times in one more than in the other. Such agents are designed with the purpose of improving image contrast between normal and abnormal tissues and may enhance the contrast positively or negatively, depending on their relative T1, T2, or T2* effects. Effec tive MR imaging contrast agents include paramagnetic (metal ions such as gadolinium, manganese, dysprosium, iron; free radicals: nitrous oxides), magnetic (superparamagnetic or ferromagnetic iron oxide particles), or diamagnetic (substances that displace hydrogen nuclei such as gases, deuterated water, perfluorocarbons) materials.The clinical effect of an MR imaging contrast medium is determined not only by the contrast-enhancing properties of the compound but also by its pharmacokinetic properties, which determine where the agent is distributed in the body and the length of time adequate concentrations are maintained in target organs. Furthermore, it is of crucial importance that the drug be well tolerated when given in doses necessary to achieve the clinical effect. Before a new chemical entity is introduced into humans as a drug, it is extensively studied in animals with respect to properties mentioned above. When the re1axivit.y effect of a contrast agent can be measured in vitro, the most important factors to study preclinically in animal experimental models are tolerance, distribution, and elimination in relevant species. The tolerance is riormally assessed during acute and subacute toxicity studies, in addition to more specific safety studies in critical organ systems such as cardiovascular, hepatobiliary, and renal systems. The safety profile is further extended through studies that examine effects on overall reproduction and on specific genetic modifications (mutagenicity), while ADME (absorbtion, distribution, metabolism, excretion) studies are performed to investigate pharmacokinetic properties. In this article, the main principles of the pharmacokinetic and toxicologic properties of the most important classes of contrast media are discussed. We focus on groups of contrast media in clinical use or under investigation; future developments such as immuno-and disease-specific concepts are not included. AGENTS DISTRIBUTED IN THE EXTRACELLULAR FLUID (ECF)Gadolinium: General Aspects the largest number of unpaired electrons and is thus, theoretically, the most efficient T1 relaxation metal that can be used in contrast media for MR imaging. However, when administered as the free gadolinium ion, the metal is not suitable as a contrast medium for three reasons: ( a ) its toxicity, ( b ) its pharmac...

MR contrast media have been used to improve MR angiography (MRA). Their effect has been particularly beneficial for extracranial MRA. This study evaluated the efficacy of a new formulation of ultrasmall superparamagnetic iron oxide particles (USPIO) on three-dimensional (3D) time of flight (TOF) MRA in the pelvis and lower limb circulation. Each of six dogs received 3 mg/kg of USPIO and .2 mmol/kg of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) bis-methylamide (BMA) by intravenous infusion on separate examinations. Precontrast and postcontrast 3D-TOF MRA images of the lower extremities were acquired over the course of 45 minutes postinjection. Signal intensity (SI) was measured on axial views along the external iliac, femoral, and popliteal arteries. USPIO provided clear demarcation of the major primary, secondary, and tertiary vessels and the improved contrast-to-noise ratio (CNR) was maintained for 45 minutes. Gd-DTPA-BMA provided less signal enhancement than USPIO. The increase in CNR with this agent had significantly declined by 15 minutes after injection. The major vessels could no longer be visualized at 30 and 45 minutes after injection of Gd-DTPA-BMA This study demonstrates the efficacy of USPIO as a contrast medium for 3D-TOF MRA. It was concluded that USPIO provided effective and persistent enhancement of the peripheral vessels.

Two phase 2 clinical trials of an oral superparamagnetic contrast agent for enhancement on magnetic resonance images of the intestine were performed. In trial 1, 31 male patients with cancer of the testis underwent follow-up examinations of the abdomen at 0.5 and 1.5 T after oral administration of magnetic particles. In trial 2, 31 female patients with pelvic and lower abdominal disease were examined at 1.5 T after administration of the contrast material. The patients each ingested 800 mL of contrast material over approximately 2 hours. Concentrations of 0.25 and 0.5 g/L did not induce blurring or metallic artifacts. Distribution was homogeneous through the gastrointestinal tract. In all patients, a loss of signal intensity was observed on proton density-, T1-, and T2-weighted images. The diagnostic information from postcontrast images in trial 2 was greater in 16 patients (52%). Contrast enhancement was independent of field strength; no major side effects were observed. Artifacts from moving bowels were less troublesome, and delineation of intraabdominal and pelvic organs was better with the use of oral magnetic particles.

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The DW imaging during early reperfusion showed a protective effect of postocclusion treatment with the free radical scavenger U74389G. The improvement of time delay to maximum effect of the contrast agent observed in the perfusion imaging of the treatment group may reflect an improvement in the collateral flow to the ischemic tissue.

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Non-biodegradable superparamagnetic particles were used as an oral contrast medium in different concentrations, and evaluated in 25 human volunteers. The aim of the study was to determine the most appropriate concentration of the contrast medium, and to evaluate the effect, distribution, safety and tolerance. With the concentration of 1.0 gil a substantial reduction of the signal intensity in the bowel was achieved in both TI and T2 weighted images. The intraabdominal structures were well differentiated from the bowels containing contrast medium. 'Metal' artifacts and blurring of adjacent structures, probably due to an increased local concentration, were observed at higher dosages. The distribution of the preparation in the gastrointestinal tract varied between individuals. As a rule a good contrast effect was achieved in the small bowel with the exception of the duodenum. The contrast medium was well accepted and did not cause any side effects of clinical importance. The results suggest that the preparation is well tolerated by humans and may be a useful contrast medium for abdominal MR imaging.