White Matter Tract Integrity (WMTI) is specific to tissue microstructure. However, answers to a question of what a decreased axon water fraction (AWF), a metric of WMTI, reflects seem contradictory among previous in-vivo and ex-vivo studies. To our knowledge, there have been no studies that compare the difference in AWF decline under both ex-vivo and in-vivo conditions. Here we use Monte Carlo (MC) simulation to investigate such question and results show that AWF decline indicated demyelination under ex-vivo conditions while it also related to axonal loss in-vivo besides demyelination. Results highlighted the non-negligible effect of membrane permeability on the difference.