Diffusion MRI enables insights into brain structure at different anatomical length scales. Although of its relative coarse millimetre image resolution it can provide a direct insight into the brain network via tractography. However, the microstructural environment such as axons can only be observed indirectly from a combination of the MRI sequence and biophysical modelling. Validation allows us to questioning the MRI sequence-biophysical modelling framework and its results that are based on assumptions on what we believe to be the ground truth. In this lecture, I will first discuss if it is possible simply by changing key sequence parameters of dMRI (b-value, directions and image resolution) to improve structural connectivity (SC) compared with tracers? Then, I will discuss axon diameter estimation with diffusion MRI, and the validation challenges we have to understand its observed deviation between the ground truth of today being 2D validation methods.
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