Spin Dynamics in spatially complex samples are determined to a large extent by the motions of molecules within the field gradients set up by spatial variations in the magnetic susceptibility. Such important characteristics as spectral image resolution, image contrast and apparent relaxation times can be related back to the length scale of motion and the correlation times of the resultant frequency modulations. This proposal is to experimentally quantify these dynamical processes through a series of novel NMR measurements. Key to the success of the study is the development and construction of a new class of NMR probes that combine MAS, three dimensional (3-D) magnetic field gradients, high spectral resolution and variable temperature capabilities. The work builds on the PI's recent success at building a MAS probe with a 1-D gradient, but adds significant engineering challenges since the two gradients transverse to the spinner axis must be electronically synchronized to the spinner's rotation. The addition of a 3-D gradient set is an essential next step since diffusive motions in biological samples are heterogeneous and anisotropic. The new experimental capabilities developed over the course of this work will make significant contributions in clinical MRI through an enhanced understanding of contrast mechanisms, and provide a new tool for ex-vivo NMR studies of tissue biochemistry, and high resolution spatial studies of biological compartmentation. A challenge in any study of heterogeneous, random processes is to select the time and length scale of the measurement so that the observed response is not governed by the central limit theorem and so that it may be related back to a unique microscopic mechanism. For NMR studies of tissue where the background gradients can be as large as a few hundred gauss per centimeter and where the diffusion constant is on the order of microns squared per millisecond, this requires that the effective length scales be sub-micron and the effective time scales be sub-millisecond. These conditions can best be achieved through the coherent averaging of MAS combined with strong pulsed gradients as proposed in this application. Following the development and construction of the hardware and the exploration of MAS based relaxation and diffusion measurements, the new capabilities will be employed to reinvestigate the spin dynamics of water in frog sciatic nerve bundles. This is a very well characterized sample, yet one where the interpretation of the mechanistic origins of the NMR signatures are still being debated.
| Chen, Jin-Hong; Enloe, Brian M; Xiao, Yong et al. (2003) Isotropic susceptibility shift under MAS: the origin of the split water resonances in 1H MAS NMR spectra of cell suspensions. Magn Reson Med 50:515-21 |
| Chen, Jin-Hong; Enloe, Brian M; Weybright, Patrick et al. (2002) Biochemical correlates of thiazolidinedione-induced adipocyte differentiation by high-resolution magic angle spinning NMR spectroscopy. Magn Reson Med 48:602-10 |
| Chen, J H; Enloe, B M; Fletcher, C D et al. (2001) Biochemical analysis using high-resolution magic angle spinning NMR spectroscopy distinguishes lipoma-like well-differentiated liposarcoma from normal fat. J Am Chem Soc 123:9200-1 |
