Noninvasive quantification of axon radii using diffusion MRI

Axon size plays a crucial role in determining conductance velocity and, consequently, in the the timing and synchronization of neural activation. Noninvasive measurement of axon radii could have significant impact on the understanding of healthy and diseased neural processes. However, until now, accurate axon radius mapping has eluded in vivo neuroimaging, mainly due to a lack of sensitivity of the MRI signal to  micron-sized axons. Here, we show how -- when confounding factors such as extra-axonal water and axonal orientation dispersion are eliminated -- heavily diffusion-weighted MRI signals becomes sensitive to axon radii. However, diffusion MRI is only capable of estimating a single metric representing the entire axon radius distribution within a voxel that emphasizes the largest axons. Our findings, both in rodents and humans, enable noninvasive mapping of critical information on axon radii, as well as resolve the long-standing debate on whether axon radii can be quantified.