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This review examines the way in which microscopic tissue parameters can affect MR experiments which are sensitive to diffusion. The interaction between the intra- and extravascular as well as that between the intra- and extracellular spaces is examined. Susceptibility gradients due to the presence of deoxyhemoglobin can cause diffusion-induced signal losses which are significant in functional magnetic resonance experiments, particularly at higher main magnetic field strengths. This is also true of the fast response that manifests itself as an early negative signal change in functional magnetic resonance experiments. The fields surrounding paramagnetic vessels are described and the way in which diffusion in these fields contributes to functional signal changes is examined. Flow in the capillary bed can be a confounding factor in experiments which aim to examine the diffusion characteristics of extravascular water. It is potentially also a method for assessing capillary perfusion. The intravoxel incoherent motion experiment is described in terms of how significantly this effect can influence diffusion attenuation curves from water. The major models for describing water diffusion in tissue are presented, as are the main experimental results that have contributed to an understanding of the mechanisms of diffusion contrast. The widely accepted view that changes in the diffusion characteristics are caused by a shift of water to the intracellular space and a concomitant change in extracellular tortuosity is examined critically. More recent experiments that indicate that a reduction in the intracellular diffusion may occur simultaneously with the cell swelling are described and their compatibility with existing models discussed.
