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Displacement MR images of water in in vitro rat spinal cord were computed from q-space analysis of high b value diffusion-weighted MRI data. It is demonstrated that q-space analysis of heavily diffusion-weighted MRI (qs-DWI) provides MR images in which physical parameters of the tissues such as the mean displacement and the probability for zero displacement of the water molecules are used as contrasts. It is shown that these MR images provide structural information surpassing the spatial resolution of conventional MRI by several orders of magnitude. This imaging methodology was used to follow spinal cord maturation in the rat. It was found that changes in the diffusion characteristics of white matter upon maturation are responsible for the emergence of gray/white matter contrast. The mean displacement of water molecules in the white and gray matter of the mature rat spinal cord was found to be 2-3, and 8-10 microns, respectively. The potential and the limitations of this new imaging methodology for early detection of white matter disorders are discussed. Magn Reson Med 44:713-722, 2000.

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Rasagiline, as the mesylate salt (TVP-1012), is a selective, potent, non-reversible MAO-B inhibitor of the propargylamine type. Current cellular and whole animal studies suggested a potential for neuroprotection by rasagiline. Rasagiline in repeat ip doses of 1-3mg/kg within 16h, or by sustained iv infusion to maintain a 3-h steady-state at corresponding levels, improved the outcome of permanent middle cerebral artery occlusion (MCAO) in the rat. In five independent studies using different protocols, rasagiline improved neurological severity score (NSS) with respect to saline from a high of 8.96 +/- 2.18 (n = 94) at 24h, and 7.64 +/- 2.52 (n +/- 49) at 48h, to a low of 7.13 +/- 2.32 (n = 88) at 24h, and 4.99 +/- 2.31 (n = 68) at 48h. Under the same conditions, there was a decrease in the volume of necrotic brain region determined at 48h by triphenyl tetrazolium chloride (TTC), from a high of 240 +/- 66 (n = 54) to a low of 176 +/- 77 mm(3) (n = 55); and by MRI scan at 48h, from a high of 297 +/- 62 (n = 25), to a low of 209 +/- 63 mm(3) (n = 28). Improvement in NSS was more obvious at 48h post MCAO, at the higher dose, when timing of drug administration was within the interval -30 min to 3 h from MCAO. A 3-h iv infusion of rasagiline caused a maximal reduction in infarct volume of about 49% of control. The (S)enantiomer of rasagiline TVP-1022, not a MAO inhibitor, was less effective, but still significantly different from saline, NSS at 48h 5.6 +/- 2.5 (n = 24) vs. 7.5 +/- 2.5 (n = 24), infarct volume 200 +/- 64 (n = 24) vs. 240 +/- 55 mm(3) (n = 24). Selegiline (n = 19) at corresponding ip doses was not different from saline. Dizocilpine decreased infarct volume from 277 +/- 65 (n = 20) to 203 +/- 52mm(3) (n = 21) but could not improve NSS at 24 or 48h. In this model, rasagiline could have exerted a neuroprotective effect independent of MAO inhibition.

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