IN-VIVO MAGNETIC-RESONANCE-IMAGING AND SPECTROSCOPY IN PHARMACOLOGICAL RESEARCH - ASSESSMENT OF MORPHOLOGICAL, PHYSIOLOGICAL AND METABOLIC EFFECTS OF DRUGS

Nuclear magnetic resonance methods are becoming recognized tools not o nly in medicine but also in experimental pharmacological research. The most widely used modality, magnetic resonance imaging (MRI), gives in sight into the morphology and is applied to determine non-invasively t he size and location of pathological structures such as tumors and inf arcts. The excellent soft tissue contrasting abilities of MRI make it for many indications superior to other imaging modalities, e.g. X-ray computerized tomography. In recent years so-called functional imaging methods have been developed, which allow the mapping of physiological parameters. Typical examples are hemodynamic measurements such as bloo d flow in large vessels and at the capillary level (tissue perfusion). These imaging methods are complemented by magnetic resonance spectros copy (MRS), which provides information e.g. on the levels of various m etabolites. The potential of MRI and MRS techniques in drug developmen t is discussed on the basis of some practical examples. In order to be come routinely established in the drug development, MRI and MRS must o bviously have some advantages over alternative techniques. Potential a dvantages, such as uniqueness of information, reduction of the number of animals required, and better cost-effectiveness, are discussed in s ome detail on the basis of selected drug studies involving MRI/MRS. Ba sed on the present status of MRI/MRS and in view of novel developments , such as brain activation mapping without the need of exogenous contr ast agents, it is foreseeable that these methods will become indispens able tools in both preclinical and clinical drug development. It is th e purpose of the present article to give an overview about in vivo NMR applications in the drug development process.