Tore Bach-Gansmo

Oral Superparamagnetic Particles for Magnetic Resonance Imaging Effect in Plain and Viscous Aqueous Suspensions

As a potential gastrointestinal MR contrast medium magnetic particles have been evaluated in preclinical studies as well as in healthy volunteers. The main problem was to achieve an even distribution of the aqueous suspension of magnetic particles in the entire intestine. To improve the distribution of the contrast medium, a viscosity-increasing agent was added to the preparation. In the plain aqueous suspension the magnetic particles sedimented rapidly and caused artifacts, whereas no such sedimentation occurred in the viscous preparation. The contrast effect, as well as the presence of artifacts, increased with particle concentration. The general contrast effect was good in all 5 volunteers, and the contrast medium was well distributed in the small intestine, including the duodenum. There were no artifacts observed, and the contrast medium was well tolerated. The viscosity-increasing agent will thus be introduced in further clinical studies.

Combination of Gadolinium and Dysprosium Chelates as a Cellular Integrity Marker in MR Imaging

A combination of gadolinium (Gd) and dysprosium (Dy) chelates was investigated as a potential marker of cell-membrane integrity by means of a double-contrast effect in MR imaging. Blood samples with varying hematocrit (Hct) levels containing intact or lysed cells were used as model systems. With intact cells, the agents were assumed to be distributed solely extracellularly and the highest Hct studied (69%) was assumed to mimic the ratio of extracellular to intracellular water in tissue. The combined effect on image intensity of Gd (in a concentration corresponding to 0.2 mmol/kg b.w. in humans) and Dy (0.6 mmol/kg b.w.) applied simultaneously was a marked difference in signal intensity between samples with intact and lysed cells in both the T1- and T2-weighted spin-echo images with a corresponding increase in the contrast-to-noise ratio. This was the result of a T1 reduction caused by Gd with a negligible Dy susceptibility effect in areas with lysed cells. On the other hand, the Dy susceptibility effect (i.e. reduced apparent T2) dominated in areas with intact cells. Thus, the combination of Gd and Dy may serve as a marker of cell-membrane integrity in MR examinations.

Superparamagnetic iron oxide for liver imaging. Comparison among three different preparations.

OBJECTIVES.The effects of differently sized superparamagnetic iron oxide (SPIO) particles as liver contrast agents were evaluated by relaxation analysis and magnetic resonance imaging in normal rabbits. METHODS.We performed relaxivity measurements in agarose gels; Tl was measured by saturation recovery. Rabbits were injected with SPIO particles to evaluate hepatocellular localization and magnetic resonance appearance. RESULTS.Small (30 nm), medium (300 nm) and large SPIO particles (3,500 nm) reduced the T2 of liver by 50%, 40% and 15%, respectively, and the T2 of spleen by approximately 60%, 65%, and 25%, respectively, at 1 mg Fe/kg intravenous injection. Both small and medium SPIO particles decreased the Tl of spleen by approximately 35%, with no effect on liver Tl. Magnetic resonance imaging showed decreased signal intensity ratios (SHiver/SImuscle) by approximately 80% and 60% for small and medium SPIO particles, respectively. Iron oxide (positive Perls blue staining) was observed in Kupffer cells after injection of medium and large SPIO particles, and also in hepatocytes after injection of small SPIO particles. CONCLUSION.The liver contrast effect seemed to be related to cellular distribution; the widely distributed small SPIO particles were most effective.

Oral magnetic particles. Results from clinical phase II trials in 216 patients.

Oral magnetic particles (OMP) have been evaluated in a clinical phase II trial program comprising 216 patients in 7 European centers. Adult patients referred for MR imaging for various abdominal pathologies were examined. The patients received OMP at a concentration of 0.1 g/l (ultralow field) or 0.5 g/l (mid/high field) and OMP was diluted in water or in a more viscous liquid formulation. Depending on the area of interest, OMP was ingested in a volume of 300 to 800 ml. OMP was well tolerated with no serious adverse events and the patient acceptability was good. OMP had a good contrast effect on all applied pulse sequences. The viscous formulation of OMP was homogeneously distributed through the entire gastrointestinal tract without inducing disturbing susceptibility artifacts. The postcontrast diagnostic information was improved in 70% of the cases. Based on the encouraging results in phase II, OMP has been advanced to phase III clinical trials.

Oral Magnetic Particles

Oral magnetic particles (OMP) have been evaluated in a clinical phase II trial program comprising 216 patients in 7 European centers. Adult patients referred for MR imaging for various abdominal pathologies were examined. the patients received OMP at a concentration of 0.1 g/l (ultralow field) or 0.5 g/l (mid/high field) and OMP was diluted in water or in a more viscous liquid formulation. Depending on the area of interest, OMP was ingested in a volume of 300 to 800 ml. OMP was well tolerated with no serious adverse events and the patient acceptability was good. OMP had a good contrast effect on all applied pulse sequences. the viscous formulation of OMP was homogeneously distributed through the entire gastrointestinal tract without inducing disturbing susceptibility artifacts. the postcontrast diagnostic information was improved in 70% of the cases. Based on the encouraging results in phase II, OMP has been advanced to phase III clinical trials.