Magnetic resonance imaging (MRI) was employed to study the rat brain in conjunction with intracerebral (ic) injection of three contrast agents: GdHAM, GdDPTA, and MnCl2. The results demonstrate several advantages of ic administration of MRI contrast agents over the other routes of injection in examining CSF dynamics and brain ventricular structure. Apparent affinity of the luminal ventricular wall of the brain for positively charged GdHAM and Mn2+ ions is observed, presumably reflecting the presence of negatively charged wall components. Respiratory distress caused by (intravenous) injection of GdHAM was found to be minimized in the case of ic injections. Time-dependent changes in observed contrast indicate that diffusive processes rather than flow of CSF play a dominant role in distributing the contrast agents. Possible applications of this approach in brain research are discussed.

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Previous studies of MRI contrast resulting from the intracerebral administration of several contrast agents have suggested that the distribution of these agents may be dependent on the net charge. In order to further evaluate the significance of this parameter, the distribution of both aquo and CDTA-chelated lanthanide and transition metal ions in the cerebral ventricles of rats has been evaluated based on their enhancement of MRI contrast. The agents were injected directly into the lateral ventricles of Sprague-Dawley rats. Each of five different positively charged paramagnetic metal ions tested selectively enhanced the inner cellular layers of ventricular luminal wall of the rat brain, while such enhancement was absent using the corresponding negatively charged metal-CDTA complexes. The abundance of negatively charged residues on the cell surface of the inner luminal layers is suggested to be the source of the observed charge affinity. Differences in the distribution of Mn2+ ions administered intracerebrally compared with intraperitoneal (ip) injection suggest that while the first treatment may result primarily in uncomplexed aquo ions which then interact with the luminal surface, manganese ions administered ip behave more like chelated ions and are most probably complexed to transferrin.