Abstract

The ability of MRI to provide three dimensional images of thick opaque samples in a noninvasive manner has made it an extremely important clinical tool. In addition, the large number of types of contrast mechanisms in a MR experiment offer the clinician and research scientist the possibility of adapting the image contrast to fit the problem of interest. While typical resolutions employed clinically are on the order of a millimeter, the notion of using MRI at microscopic resolutions arose early in the development of this technique. Spatial information is encoded in both the frequency and phase of the nuclear magnetic resonance signal by selective application of magnetic field gradients. Spatial resolution in biological samples is typically limited by a number of physical effects as well as signal-to-noise ratio (S/N) considerations. Estimate of the theoretical limits of resolution in the MR image arising from these phenomena range from 2 to 0.5μm. The practical spatial resolution is currently determined by the S/N which is often limited by the amount of time available to actually acquire the image (i.e. the temporal resolution). For example, a reasonable S/N clinical MR image can be obtained in about 5 minutes with a voxel (volume element) size of (1mm). We are interested in voxels down to ∼1μm on a side. Because most of the proton MR signal arises from water in biological samples and water concentration is roughly constant, the S/N change in the image will be proportional to the volume change: a factor of 10−9. Of course, this is true only if all experimental parameters are the same.

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