Manfred BrauerManfred Brauer
B.Sc., Calgary; M.Sc., Ph.D., Wisconsin, Madison
Email Brauer@chembio.uoguelph.ca
phone number (519) 824 -4120 x 3795
NMR spectroscopy and Imaging of biological systems. Biochemistry and toxicology of the liver.
General Overview
My group is using nuclear magnetic resonance (NMR) imaging and spectroscopy to elucidate the mechanisms of altered energy metabolism in the livers of intact, living animals non-invasively. NMR imaging 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 NMR 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 are also using 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 Magnetic Resonance Imaging 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 damand, 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).
Three state-of-the-art NMR systems are available to support these studies: a 200 MHz and 400 MHz NMR spectrometer for in vitro samples and a wide bore NMR imager/spectrometer for in vivo studies:
Students training with me will gain various skills:
1 . Whole animal manipulation, surgery, and anesthesia.
2. Chemical and biochemical analyses of cell extracts, proteins, etc.
3. Acquisition and interpretation of NMR spectra and images.
4. Software and electronics development.
5. Application of NMR to classical and contemporary biological problems.
