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Direct infusion of therapeutic agents into the brain and spinal cord is a promising local delivery method that circumvents the blood-brain barrier and blood-spinal cord barriers. Predictive models of interstitial (extracellular) distribution during direct infusion would be useful in treatment optimization and planning. To account for large infusion volumes, such models should incorporate tissue boundaries and anisotropic tissue properties. We have developed a rapid, semi-automatic computational modeling approach that utilizes diffusion tensor imaging data to predict interstitial tissue distributions of injected tracers. The developed methodology was validated for direct infusion into the dorsal white matter column of the rat spinal cord.