Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS.

Citrate-coated USPIO particles VSOP-C125 appear to have more favorable properties for magnetic labeling of macrophages than the carboxydextran-coated USPIO preparation DDM 43/34/103.

The enkephalins are derived from a common precursor protein known as preproenkephalin (ppENK). Enkephalins appear to be one of the endogenous ligands for the opiate receptors. In the rat the ventricular myocardium contains more ppENK mRNA than any other tissue. To gain further insight into the role of cardiac enkephalins, the regional and developmental distribution of ppENK mRNA was studied by Northern blotting and in situ hybridization. In the early postnatal period, ppENK mRNA is low in atrial and ventricular myocardium. With maturation, ppENK expression increases threefold in left and right ventricular tissue, but not in the atria or cardiac conductive system. Interestingly, ppENK mRNA levels are four times higher in the left than in the right chamber. Thus, to our knowledge, ppENK is the only gene exhibiting marked differences in expression between the adult right and left ventricle. Given the left-side preference of ppENK expression, the possibility is raised that the left ventricle is an endocrine organ that supplies the body with enkephalins.

Basic medicobiological research in recent years has made rapid advances in the functional understanding of normal and pathological processes down to the molecular level. At the same time, various imaging modalities have developed from the depiction of organs to approaching the depiction of the cellular level and are about to make the visualization of molecular processes an established procedure. Besides other modalities like PET and near-infrared fluorescence, MR imaging offers some promising options for molecular imaging as well as some applications that have already been tested such as the visualization of enzyme activity, the depiction of the expression of certain genes, the visualization of surface receptors, or the specific demonstration of cells involved in the body's immune response. A major advantage of molecular magnetic resonance imaging (mMRI) over other more sensitive modalities is its high spatial resolution. However, the establishment of mMRI crucially relies on further improvements in resolution and the development of molecular markers for improving its sensitivity and specificity. The state of the art of mMRI is presented by giving a survey of the literature on experimental studies and reporting the results our study group obtained during investigation on gliomas.