MRI has proven its potential for noninvasive assessment of tissue architecture. However, the achievable spatial resolution is ultimately determined by the modality's limited detection sensitivity in terms of signal-to-noise ratio (SNR). An alternative approach toward characterizing the microarchitecture of structured materials and tissues is q-space imaging. Analogous to k-space and image space representing spatial frequency and its Fourier transform -- the spectrum of spin density -- the Fourier transform of the NMR q-space signal is the spectrum of displacements. In the white matter of the spinal cord an array of axons provides a quasi-regular array of parallel cylindrical structures separated from the extracellular medium by a semi-permeable myelin sheaths which imposes barriers to diffusion. Q-space NMR currently has several limitations. The first is the amplitude of the diffusion sensitizing gradients, since qmaxdetermines the resolution in the displacement domain. For example, for a propagator resolution of 1 mu/m and a gradient duration delta=1ms Gmax= 2,200 G/cm would be required, which is more than one order of magnitude greater than gradient strengths typically available. Access to such gradient capabilities further will allow probing of very small-scale diffusion restrictions. Second, while simulations of the q-space behavior have the potential to provide physical and biological insight and enable systematic planning of experiments, such approaches demand more elaborate models than those hitherto available. The investigators have, in preliminary work, explored the above issues and propose to further develop and apply q-space methodology for the non-destructive analysis of tissue microstructure and function, focusing on the axonal structure of the rat spinal cord. The overall hypothesis underlying this proposal is that ultra high-resolution displacement imaging in conjunction with simulations of diffusion diffraction from histologic images will provide new insight into tissue architecture. The following specific aims will be pursued: 1. Complete construction and evaluate the performance of a single-axis gradient system allowing amplitudes of up to 4,000 G/cm for performing q-space imaging of small specimens at 400 MHz. 2. Simulate q-space behavior on the basis of a previously developed finite difference model for (a) synthetic models of axons as a function of distribution of axon size and membrane permeability, (b) histologic images of rat spinal cord for different white matter regions. 3. Perform high-q 3D q-space imaging in excised rat spinal cord with the objective of quantifying axonal architecture and compare the results with histology.
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