Abstract #0465

Diffusion Distinguishes Between Axonal Loss and Demyelination in Brain White Matter

Els Fieremans¹, Jens H. Jensen², Joseph A. Helpern², Sungheon Kim¹, Robert I. Grossman¹, Matilde Inglese³, Dmitry S. Novikov¹

¹Center for Biomedical Imaging, Radiology, New York University School of Medicine, New York, NY, United States; ²Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, United States; ³Neurology, Mount Sinai School of Medicine, New York, NY, United States

Non-Gaussian diffusion MRI methods provide estimates for the axonal water fraction (AWF) and tortuosity of the extra-axonal space. Using Monte Carlo simulations in a realistic geometry of the corpus callosum, we show that the AWF is most sensitive to axonal loss, whereas the tortuosity is most sensitive to demyelination. The value of this distinction is demonstrated by quantifying the degree of demyelination and axonal loss in multiple sclerosis and in Alzheimers disease (AD), where our analysis demonstrates that the change from normal to mild cognitive impairment is mainly explained by demyelination, while conversion into AD is characterized by axonal loss.