CBBS NeuroNetworks - Linking the Microscopie and Macroscopie World: Systematic Study of Water Macromolecule Exchange as a Basis for Ultra-High Field MR Phase Contrast Imaging

The proposed network will combine existing expertise in magnetic resonance imaging at ultra-high field (Zhong), high resolution NMR (Hilfert), cell biochemistry (Smalla), in vivo MR animal imaging (Angenstein), and clinical multiple sclerosis (MS) research (Matzke). This translational project is based upon the recently proposed water-macromolecule exchange (WME) model for in vivo phase contrast imaging (Zhong) suggesting that macromolecules are the major contributing factor for the recently much debated in vivo phase contrast in the brain. This contrast has generated a lot of interest since it allows for very high resolution in vivo imaging with extraordinarily strong contrast at ultra-high field strength previously not achievable with MRI. The proposed projects will establish a theoretical model for WME interaction and its effect on water frequency shift (Zhong) and relate this microscopic effect to macroscopic MR imaging experiments in animals (MS mouse model) (Angenstein). In addition, macromolecules will be characterized in different tissue types in the mouse brain and different cell fractions will be separated to access their contribution to in vivo phase contrast (Smalla, Zhong). The findings from animal studies will be further correlated with in vivo human studies in MS patients to access the potentials of phase contrast as a novel diagnostic tool for early disease detection and prediction (Matzke). The project will also extend to basic protein chemistry and will correlate WME with protein conformation changes using 2- and 3-dimentional NMR spectroscopy in an exploratory study (Hilfert, Zhong).

The proposed project will address the following main scientific questions:

• How do macromolecules interact with water?
• Is it possible to observe dynamic protein conformation changes using WME?
• What is the in vivo macromolecule distribution and its contribution to the WME frequency shift as determined by MR phase contrast imaging?
• How can the WME model be used to study quantitatively in vivo pathologies involving macromolecule alternation?
General aims: With the successful completion of the proposed projects, we will achieve the following milestones:
• Theoretical model to describe the water-macromolecule exchange.
• In vivo macromolecule characterization of brain tissues and the macromolecule contribution to the MR phase contrast.
• Correlation of macromolecule (phase image) changes with the status and prognosis of diseases, such as multiple sclerosis.