Advanced Methods to Study White Matter Microstructure

Magnetic resonance imaging (MRI) and specifically diffusion MRI opened, for the first time, a window into the in vivo physiology of white matter. Almost two decades ago, diffusion tensor imaging (DTI) provided the ability to reconstruct and characterize white matter pathways. Despite the fundamental new insights it provides, DTI has several limitations reducing the specificity and interpretability of derived indices (mean diffusivity and fractional anisotropy). Newer diffusion MRI-based frameworks such as CHARMED, AxCaliber, and ActiveAx allow more detailed investigation of white matter microstructure through the modeling of the diffusion signal. These frameworks allow extraction of more detailed microstructural parameters such as the axonal density and axonal diameter distribution. This chapter will describe the theoretical background as well as experimental aspects of the recent diffusion MRI frameworks and their potential application in the spinal cord.