  The g-ratio, quantifying the comparative thickness of the myelin sheath
encasing an axon, is a geometrical invariant that has high functional relevance
because of its importance in determining neuronal conduction velocity. Advances
in MRI data acquisition and signal modelling have put in vivo mapping of the
g-ratio, across the entire white matter, within our reach. This capacity would
greatly increase our knowledge of the nervous system: how it functions, and how
it is impacted by disease. This is the second review on the topic of g-ratio
mapping using MRI. As such, it summarizes the most recent developments in the
field, while also providing methodological background pertinent to aggregate
g-ratio weighted mapping, and discussing pitfalls associated with these
approaches. Using simulations based on recently published data, this review
demonstrates the relevance of the calibration step for three myelin-markers
(macromolecular tissue volume, myelin water fraction, and bound pool fraction).
It highlights the need to estimate both the slope and offset of the
relationship between these MRI-based markers and the true myelin volume
fraction if we are really to achieve the goal of precise, high sensitivity
g-ratio mapping in vivo. Other challenges discussed in this review further
evidence the need for gold standard measurements of human brain tissue from ex
vivo histology. We conclude that the quest to find the most appropriate MRI
biomarkers to enable in vivo g-ratio mapping is ongoing, with the potential of
many novel techniques yet to be investigated.
