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

Abstract

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.