Three-dimensional NMR microscopy: improving SNR with temperature and microcoils.

It is widely held that the spatial resolution achievable by NMR microscopic imaging is limited in biological systems by diffusion to approximately 1-5 microns. However, these estimates were developed for specific imaging techniques and represent practical rather than fundamental limits. NMR imaging is limited by the signal-to-noise ratio (SNR). Diffusion effects on spatial resolution can be made arbitrarily small in principle by increasing the gradient strength. The exponential signal attenuation from random spin motion in a gradient, however, will reduce the signal far below the noise level when the voxel size is reduced much below 5 microns. Two factors can be optimized to improve the SNR: (1) the inductive linkage between microscopic samples and the detection apparatus and (2) the temperature of the rf probe. In this work, the filling factor was optimized using inductors with diameters less than 1 mm. It is furthermore shown that probe circuit cooling results in significant improvements in SNR, whereas cooling of the preamplifier is of little value when proper noise matching between the resonant circuit and preamplifier is accomplished. Using three-dimensional Fourier imaging techniques, we have obtained images of single-cell organisms with spatial resolution of approximately 6 microns. Practical limitations include mechanical stability of the apparatus, thermal shielding between the sample and probe, and the magnetic susceptibility of the sample.