MAGNETIC RESONANCE IMAGING STUDIES OF HEAVY METAL DISTRIBUTION

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It has recently become possible to obtain spatially resolved "images" of the nuclear spins of biological and chemical materials. Magnetic resonance imaging (MRI) is rapidly evolving into an important tool for the clinical diagnosis of a wide range of human pathologies. Such imaging studies have been almost exclusively limited to the detection of protons, which provide images of the abundant protonated molecules in biological tissues: fat and water. Since image intensity is dependent on the density of protons in a given sample volume, as well as on the nuclear relaxation properties of these protons, it becomes possible to study the distribution of species which can alter these nuclear relaxation parameters. This dependence is the basis for the use of so called 'contrast agents', most typically chelated paramagnetic ions, which enhance the contrast of regions into which they are transported as a result of their effects on relaxation parameters. In general , the use of such agents may be associated with additional toxicity. We have carried out studies of the distribution of several of these compounds, including a relatively new, experimental agent: GdHam, which is somewhat unusual in that it carries a net positive charge. In contrast to previous studies in which the agents are introduced via intraperitoneal or intravenous injection, these agents were administered to rats intracerebrally via the lateral ventricle. This route of administration allowed us to study the dynamics of the cerebrospinal fluid. One interesting result of this study is that the distribution of the agents tested appears to depend on the net charge, with positively charged molecules such as GdHam tending to associate with the ventricular surfaces. In addition, intracerebral administration of GdHam minimized the respiratory distress which we have noted to be associated with intravenous intraperitoneal administration of this agent. MRI studies using intracerebrally administered nitroxides as contrast agents have also been carried out during the past year.