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During year 2 of this funding support, we have developed more tools to demonstrate that DBSI is the future of diffusion MRI and neuroimaging modality to effectively detect underlying white matter tact pathologies noninvasively. We developed an objective quantitative histology analysis approach that allows an exact match between histology images and MRI maps. For situations where co-registered MRI-histology is not available due to data acquisition difficulties, the objective quantitative analysis of histology remains readily applicable. Current preliminary results suggest that DBSI detected axonal injury, demyelination, and inflammation closely correlated with histology findings. Most interestingly, results from the shorter time course of DBSI of optic nerve from EAE mice during acute ON indicated that visual impairment did not reflect underlying severity of optic nerve damage. DBSI detects all pathologies in optic nerves during ON.