NMR Spectroscopy and Imaging of Biological Systems. Biochemistry and Toxicology of the Liver.
My group is using nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) to elucidate the mechanisms of altered energy metabolism in the livers of intact, living animals non-invasively. MRI can provide information, in spectacular detail, about the anatomy of an organ within the body. Localized in vivo NMR spectroscopy can, at the same time, provide valuable biochemical information from any defined region determined from the magnetic resonance image (see figure). We are using these techniques to study the effects of classical hepatotoxicants such as bromobenzene, the halocarbons and chronic ethanol administration on rat liver in situ. We are investigating how these toxic compounds alter hepatic water, lipid and electrolyte distribution, bioenergetic status, and the liver's ability to metabolize test compounds. We also use high resolution multinuclear one- and two-dimensional NMR spectroscopy of in vitro tissue extracts to complement the in vivo studies, and as an independent analytical technique.
An exciting extension of these studies is functional MRI based on altered deoxyhemoglobin (paramagnetic) / oxyhemoglobin (diamagnetic) ratios in the tissue to study hepatic oxygenation changes in situ. For example, metabolism of an acute dose of ethanol causes increased hepatic oxygen demand, which is compensated for in control animals (A: before acute ethanol; B: during ethanol infusion; C: difference MRI) (see figure). However, chronic ethanol treatment leads to a net increase in deoxyhemoglobin / oxyhemoglobin ratio with the same acute challenge (D. before acute ethanol; E: during ethanol infusion F: difference MRI). Our overall objective is to determine if and how functional MRI can be used to noninvasively determine whether any organ in the body is hypoxic.