The work proposed will continue to explore and demonstrate the range of applications of the effects of non-diamagnetic agents on the two strongest tissue NMR signals: those of 1H2O and 23Na-aq. The adjective non-diamagnetic is used here to indicate any magnetic behavior (ex. paramagnetic, super-paramagnetic, ferromagnetic, etc.) exhibited in addition to simple diamagnetism. Specific projects in the first general category (1H2O) are proposed. The genesis of some of these ideas derived from early work with 23Na-aq. However, now priority must be given to the former, over analogous studies of the latter. It will be demonstrated that one can make 1H2O MR images of contrast reagent (CR) distribution volumes directly, as well as cytolemmal water permeability coefficient maps, cytoplasmic; volume images, and extracellular volume maps. The latter two represent the editing of quantitative (spin density) 1H2O images for the fundamental compartmentalization of biology, which can be radically altered in pathologies such as edemas and tumors. The advance making these development possible is the new technique of combined relaxography and imaging (CRI) recently introduced by this laboratory. The CRI technique is explained in this proposal, and is totally general and applicable to longitudinal, transverse, or rotating-frame NMR relaxation. It can be used to study any CR, whether employing the hyperfine or the bulk magnetic susceptibility mechanisms (or both). Longitudinal relaxation and hyperfine CRs are emphasized in this proposal. This program has recently moved to a new institution and a significantly higher level of effort. Thus, in addition to rat experiments, studies of canine (beagle) and primate (baboon) models are proposed. These involve the programmed, stepped IV infusions of CRs approved for humans, and a quite precedented levels. The ability to study the larger animals provides the opportunity to address important issues of the scaling of the pharmacokinetics and attainable image resolution. The types of images itemized above will be examined for any tissue present in any selected field-of-view, including various muscle groups, the liver, a tumor model implanted in rat thigh muscle, the brain, and a tumor model implanted in the rat brain. The latter two require direct intracerebroventricular injection of the CR since it does not cross the blood-brain-barrier in normal tissue and this approach will be applied only to rats and dogs. The tumor models allow assessment of much greater tissue heterogeneity, and the fundamental bases of their study by the increasingly popular dynamic CR-enhanced method, which involves bolus IV injections. This work involves aspects of physics, physical chemistry, biophysics, and physiology and has ramifications in the study of a number of pathological conditions including neurological and cardiovascular disorders.
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