Diffusion MRI of tissue microstructure

4 problems

• Smallest axon diameter measurable by diffusion MRI in humans

  Partially resolved

  Most human axons are less than a thousandth of a millimetre across, near or below what the scanner gradient strength can resolve. Whether reliable axon-size maps are possible is unsettled.

• Water exchange times across cell membranes in grey matter

  Contested

  Water moves in and out of brain cells while it is being measured, which blurs the distinction between inside and outside. Reported exchange times disagree by large factors.

• Identifiability of white-matter compartment parameters from diffusion data

  Partially resolved

  Models of brain white matter describe the signal using a few water compartments, but different parameter sets fit the same data equally well. It is unclear which measurements make the answer unique.

• Structural universality class from time-dependent diffusion

  Partially resolved

  How quickly the measured water mobility settles as observation time increases depends on how the tissue structure is arranged at large scales. Which arrangement class each tissue belongs to is not established.