Evaluation of diffusion time–dependent changes in radial diffusivity as a surrogate for axon diameter

Purpose: To experimentally evaluate the change in radial diffusivity with diffusion time ((Formula presented.)) as a simple estimate of axon diameter. Methods: Ex vivo ferret spinal cords were imaged via MRI and scanning electron microscopy. Region-of-interest comparisons were made between (Formula presented.) and area-weighted mean axon diameter, (Formula presented.), derived from scanning electron microscopy. Additional comparisons were made between (Formula presented.) and quantitative MRI myelin metrics. Results: A strong linear correlation was found between (Formula presented.) and (Formula presented.). Negative correlations were found between myelin water fraction and (Formula presented.) as well as bound pool fraction and (Formula presented.). Conclusion: The value of (Formula presented.) is shown to be a good estimate of axon size in ex vivo spinal cords regardless of variations in myelin content, as indicated by quantitative MRI.