Nuclear magnetic resonance microscopy

Abstract

This thesis describes the design and applications of an improved Nuclear Magnetic Resonance (NMR) microscope, which permits MRI to study small sample sizes ( < 2mm) at high resolution (up to 2[mu]m). The effects of molecular diffusion and local variations in the magnetic susceptibility in NMR microscopy are described, which, along with the intrinsic low sensitivity of NMR, are the fundamental limitations to resolution. Molecular diffusion in the presence of a magnetization grating not only broadens the point spread function but also reduces the signal intensity. The significance of these effects depends strongly on the magnetic field gradient strengths and imaging protocols. A NMR microscope for a standard bore 14.lT magnet was developed, it is equipped with a highly efficient. solenoidal RF coil and three orthogonal gradients with strengths of 1260G / cm for Gz , 760G/cm for Gy , and 410G/cm for Gx at 15A. A modified CTI sequence is presented which incorporates strong pulsed gradients, Ernst angle excitation, CP coherent detection and reduced k-space sampling. It is the optimal pulse sequence for acquiring high-resolution ( < 5[mu]m) NMR images (best signal-to-noise ratio per unit time) when the effect of molecular diffusion is significant. It is demonstrated that this new sequence makes it possible to acquire images with a high resolution of 2[mu]m x 2[mu]m x 8[mu]m within a few hours. A wide variety of images have been acquired using the new microscope, and representative images are presented to demonstrate the potential of NMR microscopy as a new tool in developmental biology research. In particular, used in combination with other biological techniques, NMR microscopy can provide a robust, non-invasive, 3D imaging approach to quantifying changes in structure due for instance to radiative exposure, therapy, and natural growth or genetic modifications.